Endoscopic Treatment of Achalasia Free

Achalasia is the most frequent esophageal motility disorder, characterized by an impaired lower esophageal sphincter (LES) relaxation and absent or ineffective peristaltic contractions [1, 2]. Usually, patients with achalasia experience dysphagia to both solid and liquids, regurgitation of food and saliva, chest pain, heartburn and weight loss [3]. Endoscopy, timed barium esophagogram and esophageal high-resolution manometry are used for the diagnosis of achalasia [2]. Endoscopic treatment of achalasia is focused on alleviating the hypertonicity of the LES through different approaches such as peroral endoscopic myotomy (POEM), pneumatic dilation (PD), and botulinum toxin injection (BTI). However, there is no available treatment for recovering esophageal ineffective peristaltic contractions.

Since the first case series of patients published by Inoue et al. [4] in 2010, POEM has become the standard treatment for achalasia, replacing laparoscopic Heller myotomy (LHM) as the preferred treatment for these patients. In the recent years, multiple variations of POEM technique have been explored and unresolved controversies remain to be elucidated. The aim of this review article was to discuss the latest advances, variations, and updated evidence regarding the efficacy and safety of available endoscopic treatments for achalasia.

PD involves intraluminal inflation of a 30–40-mm balloon over a guidewire at the level of the LES under fluoroscopic guidance, aiming to disrupt muscle fibers and reduce sphincter pressure, thus facilitating smoother passage of the food bolus (shown in Fig. 1). Achieving optimal clinical outcomes typically requires multiple dilation sessions over time. The interval and number of sessions are usually tailored to the patient's response, with clinical assessment (e.g., Eckardt score) and manometric evaluation. It is considered a safe and effective treatment option for achalasia and is technically simpler and quicker to perform than POEM.

In a meta-analysis of 52 uncontrolled studies including 4,166 patients, clinical success defined as an Eckardt score ≤3 was achieved in 83% (95% CI: 79–85%) of patients, though significant heterogeneity was noted across the studies [5]. Reported adverse events included perforation in 2.8% (95% CI: 2.3–3.5%), bleeding in 2% (95% CI: 1–4%), and gastroesophageal reflux disease (GERD) in 9% (95% CI: 5–16%) of patients. A multicenter randomized controlled trial (RCT) involving 133 treatment-naïve patients newly diagnosed with achalasia compared PD (30–35 mm) with POEM [6]. In terms of safety, no serious adverse events were observed in patients undergoing POEM, whereas two serious adverse events, including one perforation, were reported in the PD group. At 5-year follow-up, POEM achieved a significantly greater success rate of 81%, providing more sustained symptom relief than PD, which had a success rate of 40% [7]. However, the study design limited the number of PD sessions, permitting a second session only if the Eckardt score remained above 3 or if manometry documented an integrated relaxation pressure greater than 10 mm Hg. Other observational studies have reported comparable success rates, particularly in patients with type I and II achalasia [8, 9].

Botulinum toxin inhibits acetylcholine release at the neuromuscular junction, resulting in muscular paralysis. Endoscopic injection of botulinum toxin temporarily reduces LES pressure, providing transient relief of achalasia symptoms that can lasts several months (shown in Fig. 2). The Botulinum toxin is administered intramuscularly at the LES in four quadrants using an endoscopic needle. It is considered a safe and easy procedure, with very uncommon adverse events such as allergic reactions or mediastinitis [10]. However, given the temporary effect over LES pressure and the need for repeated treatments, generally is reserved for patients who are not candidates for more definitive treatments. A meta-analysis of 22 observational studies reported a success rate of 77% (95% CI: 72–81%) over a follow-up of 1–6 months [5]. A multicenter trial evaluating different doses of botulinum toxin demonstrated that two injections of 100 U administered 30 days apart, provided the most effective and sustained symptom relief, with up to 68% of patients remaining in remission at 24 months of follow-up [11].

Due to its favorable efficacy and safety profile, POEM has become a first-line treatment option for patients with achalasia. In particular, for patients with type III achalasia, POEM is considered the preferred treatment due to its superior efficacy compared to other endoscopic alternatives such as PD and BTI, as well as surgical options like LHM. POEM was initially described for the treatment of symptomatic, non-sigmoid achalasia [4]. With accumulating evidence supporting its safety and efficacy, the indications have expanded to include sigmoid achalasia, persistent or recurrent achalasia after surgical myotomy, and other spastic esophageal motility disorders [5, 12‒15].

Absolute contraindications to POEM include nonreversible severe cardiopulmonary conditions, coagulopathy, malignancy, or medical illness that precludes general anesthesia. Relative contraindications include extensive esophageal radiation, severe actinic injury of the esophagus, prior ablation therapy or mucosectomy in the intended POEM field, and portal hypertension with esophageal varices [1].

The general sequence of events for performing POEM include (shown in Fig. 3) the following.

Given the presence of distal esophageal outlet obstruction, it is common to observe retained esophageal food debris in patients with achalasia. In this context, a liquid diet may be recommended for up to 5 days or longer prior to the procedure, depending on the severity of esophageal stasis. Additionally, esophageal candidiasis may occur due to retained contents and delayed esophageal clearance; therefore, some centers routinely implement antifungal prophylaxis prior to the procedure.

Antithrombotic agents are typically discontinued in patients receiving them for primary prevention. In contrast, for patients receiving antithrombotic therapy for secondary prevention, POEM can often be performed without discontinuing these agents, although there may be a slightly increased bleeding risk [16‒18]. In patients on dual antiplatelet therapy, temporary interruption of the P2Y12 receptor inhibitor (e.g., clopidogrel or prasugrel) while continuing ASA is commonly considered. Current ACG-CAG guidelines support this strategy and recommend continuing ASA monotherapy in patients undergoing high-risk endoscopic procedures, such as POEM, when used for secondary cardiovascular prevention [19]. For patients on anticoagulants, direct oral anticoagulants such as apixaban or rivaroxaban are generally held 2 days before and resumed 2 days after the procedure, whereas warfarin is usually stopped 5 days before. Bridging with low molecular weight heparin may be considered only in patients at high thromboembolic risk (e.g., mechanical heart valves or recent thromboembolism), ideally in consultation with an anticoagulation clinic or specialist. The perioperative antithrombotic management in patients undergoing POEM should be individualized, balancing bleeding risk with thromboembolic risk. Current guidelines support continuing aspirin for secondary prevention and suggest temporary interruption of P2Y12 inhibitors or direct oral anticoagulants, with bridging reserved for select high-risk patients [19].

Endotracheal intubation with subglottic suctioning is essential and standard practice during POEM procedures to prevent aspiration [20, 21]. Insufflation with low-flow CO₂ and the use of positive airway pressure are also essential measures to prevent insufflation-related adverse events during POEM [22].

Although no studies have directly compared the supine and left lateral positions for performing POEM, many experts recommend the supine position [23]. In the supine position, the angulations of a dilated or sigmoid esophagus due to achalasia are less pronounced than in the left lateral position. Additionally, in the left lateral position, the weight of the liver compresses the gastroesophageal junction (GEJ), making dissection at this level more challenging. In the supine position, the endoscope rests in a stable position, facilitating myotomy. One drawback of the supine position is that, due to gravity, water may accumulate in dissection or myotomy plane if a posterior approach is used. After positioning the patient, a thorough esophageal lavage should be performed before initiating POEM, using water and antifoaming agents such as simethicone.

Prior to the mucosal incision, the esophagus must be carefully examined, and critical landmarks identified, including the upper esophageal sphincter, left main bronchus, aortic arch, and LES. Orientation along the anteroposterior axis is crucial for performing an accurate tunneling technique. Given the esophageal dilation commonly observed in patients with achalasia, vertebral bodies can be visualized to indicate the posterior midline, while the trachea serves as a marker of the anterior midline.

A small amount (5–10 mL) of saline or a viscous lifting agent, mixed with indigo carmine or methylene blue, is injected into the submucosa to create a cushion that facilitates a safe mucosal incision. Incision and tunneling of anterior vs. posterior wall of the esophagus is discussed later. For posterior POEM, most commonly performed in the 4–5 o’clock position, a longitudinal 15–20-mm incision is made in the elevated mucosa to allow trimming and entry into the submucosal space to begin tunneling. Targeting strictly the 5 o’clock position places the entry point closer to the gastric sling fibers, increasing the risk of severing these fibers and unintentionally extending into the posterior gastric wall. To minimize this risk, we and other experienced operators recommend the 4–5 o’clock position. Some centers perform transverse mucosal incision to allow for easier submucosal tunnel entry, but this approach may result in a more challenging closure. Nevertheless, no significant differences have been observed between both techniques in terms of entry time, closure time, number of clips needed to close the incision or gas-related events [24].

After making the mucosal incision, the submucosa should be carefully trimmed to obtain clear access to the submucosal space. During the tunneling of the esophagus, attention must be paid to orientation to ensure straight advancement and avoid spiral progression. Maintaining a perpendicular advancement in respect to the circular fibers of the muscularis propria can help avoid deviation from the intended direction. Precoagulation of penetrating vessels should be performed to avoid bleeding during the tunneling.

Due to the hypertonicity of the GEJ, the submucosal tunnel becomes tighter, requiring careful maintenance of adequate space to ensure safe passage to the gastric side. At this stage, it is crucial to remain within the submucosal plane and avoid entering the intermuscular space, as doing so may result in an incomplete myotomy. Additionally, the presence of accessory longitudinal muscle fibers at the GEJ may difficult the proper orientation, necessitating meticulous inspection and repeated withdrawals to preserve the correct dissection trajectory. Another challenge is ensuring that the tunnel fully extends across the GEJ. To overcome this challenge, the double-scope technique has been proposed. In this technique, a second and thinner endoscope retroflexed to provide a subcardial transilluminated view and guide passage through the GEJ. A RCT evaluating this technique reported an increase in myotomy extension in 34% of cases, although it was associated with a 17-min increase in median procedure time. Consequently, this technique should be reserved for cases where anatomical landmarks are unclear, ensuring a complete gastric myotomy during POEM [25]. Another potential adjunctive measure to ensure adequate extension of the myotomy onto the gastric side includes the use of functional luminal imaging probe (FLIP), which may help guide the appropriate length of the myotomy [26].

Despite the posterior approach being the most common for POEM in achalasia, no significant differences have been observed between the anterior and posterior approaches in terms of procedural efficacy [27‒29]. In the posterior approach, the muscularis propria is positioned neutrally in the inferior hemisphere of the endoscopic view. Since the instrument channels in the endoscope are generally located between the 5 and 7 o’clock positions, this alignment minimizes the need for excessive angulation of the endoscope tip during tunnel creation and myotomy, thereby reducing the risk of the knife “flinging” into the mucosa on the contralateral wall during the myotomy. Posterior approach has been associated to shorter time [30] and a lower risk of mucosa injury (mucosotomies) during the myotomy contrasted with anterior approach [31].

Tight closure of the mucosal incision and careful inspection for mucosal thermal injury, which may occur during submucosal tunneling or myotomy, are essential to prevent delayed complications. Proper placement of the first clip is crucial for effective closure. It should be positioned slightly beyond the distal margin, grasping symmetrical amounts of tissue to create a fold that facilitates easier deployment of subsequent clips. For placement of the following clips, the previously placed clip should be gently lifted using the endoscopic hood and the next clip positioned adjacent to it, ensuring symmetrical and secure closure. An asymmetrical closure may lead to the formation of a mucosal pocket, which in turn can result in tunnel infection and rupture of the incision site [32]. Usually 4 to 6 clips are needed for complete closure of the defect. In a RCT comparing longitudinal vs. transverse incision, no differences were observed in the number of clips needed for closure of mucosal incision [24].

Post-procedure management after POEM for achalasia includes short-term inpatient observation to monitor for complications such as pneumomediastinum, subcutaneous emphysema, or mucosal leaks. A liquid diet is recommended for the first few days, followed by gradual reintroduction of solid foods. Patients typically receive a proton pump inhibitor (PPI) to prevent GERD symptoms and to protect against mucosal damage in the area of undermined mucosa. A single dose of antibiotic appears adequate for infection prophylaxis, although evidence is limited; however, a short course of antibiotics may also be considered [33, 34]. In terms of post-procedural pain, the addition of intraprocedural tunnel irrigation with 30 mL 0.2% ropivacaine did not lead to reduced post-POEM pain [35]. Interestingly, patients undergoing POEM randomized to receive intraoperative magnesium had sustained reductions in esophageal discomfort severity and opioid requirements 24 h after procedure [36].

There is limited standardization post-POEM management. Although performing a routine post-POEM esophagogram to rule out leaks is common practice, the supporting evidence for this approach is limited due to low specificity and a high false-positive rate [37]. Current guidelines recommend performing an esophagogram only in cases of clinical suspicion or according to local protocols [15].

The utility of second-look endoscopy was evaluated in a retrospective study involving 497 consecutive patients undergoing POEM, where clinically relevant new adverse events or deviations from the normal postoperative course were identified in only 12 patients (2.4%). Multivariable regression analysis revealed that longer procedural time and the occurrence of intraprocedural adverse events were independent predictors for clinically significant findings during second-look endoscopy [38]. As a result, clinical guidelines recommend second-look endoscopy for select patients based on these identified risk factors [15].

However, we suggest that operators who are within their learning curve period should routinely perform second-look endoscopy. This practice facilitates familiarity with normal post-procedural appearances and enhances the operator’s ability to recognize atypical or adverse findings requiring intervention.

Routine admission post-POEM is not universally required. However, admission is recommended if persistent pain, nausea, or vomiting occur despite treatment. Patients eligible for same-day discharge must have no procedural complications, be asymptomatic, have adequate social support, and reasonable access to specialized care. Patients discharged on the same day should be contacted within 24–48 h to monitor for adverse events, with clear instructions for emergency care if severe symptoms arise [39].

Follow-up includes clinical assessment of symptom relief using validated scores, mainly Eckardt symptom score, as well as objective testing, such as endoscopy, high-resolution manometry, timed barium esophagogram, and pH monitoring, to evaluate esophageal function and detect GERD.

Patient-reported outcomes, such as the Eckardt symptom score, have several limitations, including subjectivity, variability, potential bias, limited scope, and possible discordance with objective assessments. Up to 30% of patients who report symptom relief following achalasia treatment continue to demonstrate poor esophageal emptying on objective evaluation, which may predict symptom recurrence [40]. Recently, Tarf et al. [41] reported that Eckardt symptom score yielded fair validity and reliability. Additionally, dysphagia accounted for 90% of the variance in the score, suggesting that the other components may not meaningfully contribute to the overall assessment [41]. In this context, clinical evaluation should be complemented by endoscopy to confirm GEJ patency and assess for esophagitis. Objective tests, such as timed barium esophagogram, should also be considered to evaluate esophageal emptying, especially when symptoms persist or recur [12‒15]. Novel predictors of treatment response have also been proposed, particularly esophageal distensibility assessed by FLIP [42]. However, further studies are needed to validate this tool for routine clinical use in assessing treatment response in patients with achalasia.

An increased risk of squamous carcinoma has been described in patients with achalasia [43, 44]. However, most endoscopic societies do not advocate for routine endoscopic surveillance in these patients due to the lack of evidence demonstrating improved outcomes. Beyond the risk of carcinoma, other considerations for endoscopic surveillance include GERD related to POEM or the progression to megaesophagus. Therefore, endoscopic surveillance every 3 years may be reasonable for patients who have had achalasia for more than 10–15 years [5, 13, 45].

Due to the mechanism of action of POEM in treating achalasia via reducing LES pressure while ineffective esophageal motility persists, GERD is a common adverse event; however, it is usually manageable and rarely leads to severe complications. In a 5-year follow-up of a RCT comparing POEM with PD for the treatment of achalasia, PPI use was significantly higher in POEM group compared to the PD (46% vs. 13%; p = 0.008) [7]. Esophagitis was observed in 33% of patients treated with POEM: 29% were grade A or B, 5% grade C and 13% grade D; however, no serious adverse events were reported up to 5 years. Compared to LHM, endoscopic significant esophagitis has been described after 24 months in 44% of the patient’s undergoing POEM and 29% undergoing LHM, respectively [46]. In the 5-year follow-up of this RCT, the incidence of significant esophagitis (Los Angeles grades B, C, or D) decreased over time in the POEM group, while it increased in the LHM group. Consequently, the GERD rates between the two procedures progressively converged, resulting in no statistically significant difference at the 5-year follow-up [47]. Moreover, some clinical guidelines recommend considering endoscopic screening for erosive esophagitis or Barrett's esophagus after POEM and advising patients that lifelong acid suppression therapy may be necessary [13].

Other rare severe adverse events, such as pneumomediastinum, bleeding, or mucosal leaks, may also occur after POEM. In the RCT reported by Werner et al. [46], serious adverse events occurred in 2.7% of patients in the POEM group and 7.3% of patients in LHM group.

The optimal myotomy length remains uncertain. Typically, a myotomy measures 10–12 cm, with 2–3 cm comprising the gastric component (cardiomyotomy). An incomplete cardiomyotomy is a common cause of symptom recurrence or treatment failure; however, extending the gastric myotomy beyond 2.5 cm may increase GERD risk without improving clinical outcomes [48]. A post hoc analysis of a RCT evaluating the double-scope technique supports this, showing increased moderate-to-severe esophagitis (Los Angeles Grade B or higher) with longer gastric myotomies (>2.5 cm) [49].

The optimal esophageal myotomy length also remains controversial. A non-inferiority RCT comparing long (13 cm) versus short (8 cm) esophageal myotomies found similar clinical success rates and GERD incidence between groups. Notably, the short myotomy significantly reduced procedure duration (40 vs. 50 min; p < 0.0001) [50]. Additional studies confirm these findings, showing equivalent efficacy and safety but shorter procedure times with shorter esophageal myotomies [51‒53].

An ongoing debate exists regarding whether to perform selective myotomy (circular muscle only) or full-thickness myotomy (circular and longitudinal layers). Observational studies report similar short-to-medium term clinical efficacy between both methods based on the Eckardt symptom score. However, full-thickness myotomy has been associated with shorter procedure times but a higher risk of GERD and postoperative pain, as well as longer hospital stays [54‒57]. Additionally, increased length of full-thickness myotomy independently predicts GERD esophagitis within 1 year after POEM (OR: 1.1 per cm; 95% CI: 1.02–1.21) [58]. Furthermore, in a retrospective observational multicenter study, full thickness was associated with more postoperative pain and a longer length of hospital stay [59]. Thus, a selective circular myotomy with limited extension is generally recommended.

Anterior and posterior tunneling approaches are both utilized in POEM procedures; however, posterior tunneling has become increasingly common in recent years. The anterior approach naturally preserves sling fibers, potentially reducing the risk of post-procedural GERD. Conversely, the posterior approach positions the scope tip neutrally in the supine patient, minimizing tension on the mucosal flap and typically resulting in shorter procedure times [15]. A randomized clinical trial (RCT) conducted by Khashab et al. [28] found that the posterior approach was noninferior to the anterior approach regarding clinical success or adverse events, including GERD, at 1-year after the procedure. Similarly, a meta-analysis by Mohan et al. [30] concluded that both approaches have comparable clinical success rates, GERD incidence, and adverse event, although the posterior approach was associated with a shorter procedure time. A recent systematic review observed a trend toward lower GERD incidence, based on endoscopically confirmed macroscopic esophagitis, in patients undergoing anterior or circular myotomy. This finding suggests the anterior approach may be preferable in select patients [60].

Sling fibers contribute to the antireflux barrier at the angle of His [61]. A modified posterior myotomy preserving sling fibers appears to significantly reduce the incidence of esophagitis compared to conventional posterior myotomy technique [62]. In this modified approach, the second gastric penetrating vessel serves as an anatomical landmark to orientate the optimal myotomy site for preserving sling fibers. This technique was associated with a significantly lower incidence of Los Angeles grade B or higher esophagitis 3 months after POEM compared to the conventional myotomy approach (31% vs. 58%; p = 0.017). These results were subsequently confirmed in another observational study [63]. However, a RCT comparing conventional versus oblique fiber-sparing endoscopic myotomy demonstrated no significant effect on GERD prevention [64]. However, it is possible that the lack of differences may be due to the preservation of oblique fibers in both groups [65]. Recently, an observational study conducted in a Western population demonstrated, through multivariable regression analysis, that the sling fiber-preserving technique was independently associated with a lower risk of GERD symptoms after POEM 0.24 (95% CI: 0.07–0.85), while maintaining similar clinical efficacy (89.5% vs. 83.1%, p = 0.32) and procedure time (108.6 ± 34.5 vs. 109.1 ± 45.7 min, p = 0.93) [66]. A meta-analysis of studies evaluating sling fiber-preserving techniques supports this approach for GERD prevention [67]. However, further multicenter RCTs with larger sample sizes are needed to draw more robust and reliable conclusions.

The addition of fundoplication after POEM aims to restore the antireflux barrier compromised by the myotomy. A novel fundoplication approach has been described using the principles of Natural Orifice Transluminal Endoscopic Surgery (NOTES). This POEM Combined with Endoscopic Fundoplication (POEM-F) approach showed reduced reflux symptoms and stable fundoplication wrap integrity in their initial series of 21 patients at 1-month follow-up [68]. Subsequently, a report of 25 patients showed that POEM-F was technically successful in 92% of the patients and resulted in a low incidence of GERD at 12 months follow-up, with abnormal esophageal acid exposure observed in only 11.1% of patients [69]. A meta-analysis of available patient series undergoing POEM-F demonstrated the feasibility and safety of POEM-F, with a significant reduction in the incidence of esophagitis of 18% (95% CI: 11–30%) during follow-up [70]. However, RCTs are needed to confirm the efficacy of this technique.

There are no RCTs directly comparing POEM with BTI. However, a network meta-analysis including 24 studies comparing different treatment modalities for achalasia, showed a significantly higher efficacy of POEM compared to BTI (OR: 11.3; 95% CI: 3.75–34.27) [71]. RCTs have evaluated the efficacy of BTI in the treatment of achalasia compared with other treatment modalities. In one RCT comparing BTI with PD, PD was superior in achieving long-term remission at 12 months [72]. Additionally, another RCT comparing BTI with LHM demonstrated that LHM provided superior long-term symptom relief [73]. Collectively, these studies indicate that while BTI can be effective in the short term, other treatments modalities offer more durable outcomes for patients with achalasia.

In a Western multicenter RCT comparing the efficacy of POEM and PD as first-line treatment for therapy-naïve patients with achalasia [6], no serious adverse events occurred in the POEM group, while one perforation (1.5%) was reported in the PD group. A 5-year follow-up demonstrated a success rate (Eckardt score ≤3) of 81% for POEM and 40% for PD [7]. Despite the higher success rate reported for POEM, the study had some limitations. The PD protocol was restricted to 1–2 attempts using 30–35-mm balloons. Previous studies have demonstrated improved success rates with PD when additional dilation sessions and larger balloon sizes (up to 40 mm) were used, tailored to patient symptoms [74]. A retrospective study comparing POEM and PD in China demonstrated similar short-term success rates between both treatments (95% vs. 96% at 3 months). However, in the long term, POEM showed a higher success rate (60% vs. 93%), with statistical significance observed only for type III achalasia [8]. Most recently, a network meta-analysis including 24 studies, POEM demonstrated significantly higher clinical success rates compared with PD (OR: 3.75; 95% CI: 1.47–9.54) [71].

Efficacy of POEM has also been compared with PD as a rescue option for patients with persistent or recurrent symptoms after LHM. In a RCT of 90 patients with residual or recurrent symptoms (Eckardt score >3) and significant stasis (≥2 cm on timed barium esophagogram) after LHM, POEM demonstrated a higher success rate compared with PD (62.2% vs. 26.7%; Odds ratios of success 2.3; 95% CI: 1.37–3.99) [75]. Two recent meta-analyses, confirmed these findings, demonstrating the efficacy of POEM as a rescue therapy for patients who remain symptomatic or experience recurrent symptoms after LHM [76, 77].

Two RCTs have been conducted comparing the efficacy of POEM and LHM for the treatment of achalasia [46, 78]. A RCT assigned symptomatic achalasia patients to treatment with either POEM (n = 112) or LHM plus Dor’s fundoplication (n = 109). The primary outcome, an Eckardt symptom score ≤3 at the 2-year follow-up, was achieved by 83% of patients in the POEM group and 81.7% in the LHM + Dor’s group, demonstrating the non-inferiority of POEM (p = 0.007) [46]. A smaller RCT comparing POEM and LHM in 40 patients showed similar results, with no significant difference in success rates at the 12-month follow-up (p = 0.242). However, higher rates of reflux esophagitis were observed in the POEM group at 12 months (p = 0.002) [78]. In a network meta-analysis of 24 studies including nearly 2,000 patients, no significant differences in clinical efficacy or reflux outcomes were observed between POEM and LHM with Dor fundoplication [71].

Less clinical experience and evidence are available to assess the efficacy of POEM in non-achalasia esophageal motility disorders (NAEMDs). Currently, no RCT have evaluated POEM in this clinical setting. However, meta-analysis of observational studies suggests a clinical success rates of 87% across all motility disorders [79, 80]. A recent meta-analysis evaluating different esophageal motility disorders suggested higher success rates with POEM in patients with distal esophageal spasm and esophagogastric junction outflow obstruction, compared to those with hypercontractile esophagus [79]. Preserving the LES during POEM for NAEMDs has gained attention, given that LES its relaxation is typically unaffected in these patients. In a recent retrospective study of 227 NAEMD patients undergoing POEM, those treated with LES-preserving techniques (n = 16) demonstrated clinical success over 24 months, with a low incidence of esophagitis [81]. However, further studies with longer follow-up are needed as some patients may eventually develop achalasia with LES dysfunction [82].

Appropriate training is a critical aspect of mastering the POEM technique, and several studies have explored its learning curve and training requirements. A structured curriculum emphasizing organized educational programs has been proposed to ensure adequate skill acquisition. These programs typically include theoretical sessions, hands-on training, and supervised procedures, which are essential components for achieving proficiency in POEM. Comprehensive POEM training must encompass technical, non-technical and cognitive skills, including pre-procedural evaluation, equipment preparation, sedation management, procedural techniques, post-procedural follow-up, and the prevention, recognition, and management of adverse events [83].

Preclinical training using animal models has proven valuable for developing technical skills and reducing complications, with at least 26 procedures recommended before performing POEM in patients [84]. Regarding the learning curve, expert endoscopists require at least 13 procedures to reach an initial learning plateau, with procedure time significantly decreasing with experience, ultimately stabilizing at approximately 102 min [85]. Furthermore, efficiency in POEM has been reported to be achieved after approximately 40 procedures, while mastery is typically attained after 60 cases [86]. Although operator experience significantly influences procedure time, clinical outcomes remain favorable regardless of experience level, underscoring the inherent safety of the technique when performed with proper training. Overall, available evidence emphasizes that mastering POEM requires structured training programs, preclinical practice, and progressive clinical experience, with continuous practice and supervised procedures as fundamental components for achieving competence.

Future research on POEM should address several key aspects. Currently, POEM treatment success is predominantly defined by achieving an Eckardt score of 3 or less. However, as discussed, patient-reported outcomes have inherent limitations. Therefore, future studies and clinical practice guidelines should emphasize clearly defined follow-up criteria incorporating both subjective and objective measures. GERD remains a primary adverse event associated with achalasia treatments; however, universally accepted definitions for post-treatment GERD are lacking. As a result, reliable predictors and effective prevention strategies are also limited. Identifying better predictors and developing strategies for reflux prevention are crucial for improving patient outcomes. In this context, further validation of GERD-preventing techniques, such as sling fiber preservation and POEM-F, are needed. Additionally, predicting procedural difficulty [87, 88] and accurately defining the learning curve for POEM [89] are essential for the broader, high-quality adoption and implementation of this technique. Ongoing research efforts should prioritize optimizing procedural techniques, establishing comprehensive follow-up protocols, enhancing training methodologies, clearly defining GERD, and identifying reliable predictors of long-term outcomes to improve both the efficacy and safety of POEM.

POEM has emerged as a highly effective and minimally invasive treatment for achalasia, demonstrating excellent clinical success and durability. Its safety profile and the ability to perform a tailored myotomy make it particularly advantageous over alternative treatment options. However, GERD remains a significant and controversial concern. Future research should focus on optimizing the POEM technique, defining standardized follow-up protocols, enhancing training frameworks, and identifying predictors of long-term outcomes to further improve both the efficacy and safety of this promising therapy.

Other treatment modalities, such as PD and LHM, remain viable options in selected patients. PD offers a less invasive and technically simpler approach but generally requires repeat sessions and is associated with lower long-term efficacy. LHM, particularly when combined with a fundoplication, provides durable symptom relief with an antireflux mechanism, but involves a more invasive surgical approach. BTI remain a valuable palliative option in patients unfit for more definitive therapies, though its efficacy is typically short-lived.

Gonzalo Latorre has no conflicts of interest to declare. Robert Bechara is Olympus’ and Vantage’s consultant.

This study was not supported by any sponsor or funder.

Gonzalo Latorre and Robert Bechara performed the literature search, selected the relevant studies, completed data extraction, and wrote the manuscript. All authors approved the final version for submission.