Advances and challenges in peroral endoscopic myotomy: Safety, precision, and post-procedure management

Abstract

Peroral endoscopic myotomy (POEM) has revolutionized the treatment of upper gastrointestinal tract motility disorders, particularly achalasia. This editorial explores the efficacy, safety, and challenges of POEM, emphasizing its role as a primary treatment with excellent long-term outcomes and minimal adverse events. The evolution of POEM underscores the need for precision in myotomy techniques and the importance of interdisciplinary collaboration, especially regarding anesthetic considerations. Despite significant advances, challenges remain in standardizing safety protocols and managing complications. As POEM applications expand, precision endoscopy continues to enhance therapeutic outcomes, promising a transformative impact on gastrointestinal motility disorder management.

Key Words: Peroral endoscopic myotomy; Complications after peroral endoscopic myotomy; Procedural safety; Interdisciplinary collaboration; Adverse events; Therapeutic outcomes

Core Tip: Peroral endoscopic myotomy (POEM) has emerged as a transformative treatment for upper gastrointestinal motility disorders, offering significant long-term efficacy with minimal adverse events. Keys to its success include precision in myotomy techniques, interdisciplinary collaboration for enhanced safety, and ongoing efforts to standardize protocols and manage complications. As POEM techniques advance and applications broaden, they promise to revolutionize the management of motility disorders.

INTRODUCTION

Peroral endoscopic myotomy (POEM) has revolutionized the treatment of upper gastrointestinal tract (UGT) motility disorders, particularly achalasia, showing excellent long-term outcomes with few adverse events (AEs). Initially developed as a novel solution for esophageal motility disorders, POEM has now become a primary treatment for achalasia, advancing toward patient-specific myotomy techniques[1,2]. However, as POEM evolves, precision in customizing myotomy to individual needs remains crucial to avoid complications and optimize outcomes[3-5].

Anesthesia management is essential for procedural safety, with studies supporting the use of general anesthesia over sedation to minimize risks. Close collaboration between endoscopists and anesthesiologists helps address potential physiological changes, enhancing patient safety[2,6]. However, the lack of standardized protocols for assessing and classifying safety outcomes suggests that there is an urgent need for comprehensive clinical trials to define a clear risk-benefit profile for POEM[6,7].

As POEM expands to address a broader range of UGT motility disorders, precision becomes critical, particularly with applications such as Zenker's diverticulum management[5,7,8]. Managing complications, including gas-related events and mucosal injuries, emphasizes proactive strategies for prevention, diagnosis, and treatment. The shift to carbon dioxide (CO₂) insufflation, for example, has notably reduced gas-related issues[6-8].

The effective management of potential AEs, such as esophageal leakage and delayed bleeding, is key to patient safety. While POEM maintains high technical and clinical success rates, ongoing collaboration, robust clinical trials, and precision-driven techniques are essential to refine protocols and enhance safety in managing UGT motility disorders[1,4,7-9].

EVOLUTION OF THE VARIOUS TECHNIQUES IN ACHALASIA MANAGEMENT

In 1914, Heller introduced the first transabdominal cardioplasty, performing a myotomy on both cardia walls. Groeneveldt and Zaaijer later simplified it to a single myotomy. The transabdominal approach dominated until the 1960s, focusing on dysphagia relief, with reflux management added later by Nissen (360° fundoplication, 1956) and Dor (180° anterior fundoplication, 1962).

Minimally invasive techniques emerged in the 1990s, with Cuschieri performing the first laparoscopic myotomy in 1991. Pellegrini’s 1992 study showed good results with thoracoscopic myotomy but resulted in reflux in 60% of cases, leading to its combination with laparoscopic fundoplication. By 1993, laparoscopic myotomy with Dor fundoplication became the standard, offering faster recovery and shorter hospital stays compared to open surgery. POEM and laparoscopic Heller's myotomy (LHM) are both effective treatments for achalasia and should be considered for all patients. LHM is typically performed for patients with type I and type II achalasia, especially those who are overweight and have a hiatal hernia, as adding a fundoplication helps control reflux in most cases. For type III achalasia, POEM is recommended as the initial treatment. If POEM fails, pneumatic dilatation (PD) is the next option. If PD fails, POEM can be considered for patients who initially had LHM, and LHM for those who had POEM. Esophagectomy is reserved as a last resort for patients with persistent symptoms after other treatments have failed[10].

AES

While POEM is generally considered safe, it can have both major and minor AEs during the procedure. Intra-procedural AEs can include mucosal perforations, pneumothorax, pneumoperitoneum-capnoperitoneum, among others. While most of these events are self-limiting and resolve during the procedure with endoscopic treatment, major AEs occur in 1.2% to 2.2% of cases. POEM's safety extends to more complex scenarios, including patients with prior surgical treatment. Gastroesophageal reflux disease (GERD) is a significant long-term concern after POEM, with rates varying between studies. Teh et al[11] reported a high incidence of reflux esophagitis post-procedure, particularly compared to PD, which is similar to POEM. Comparative studies between POEM and other treatments like LHM have shown similar clinical success rates but differences in AEs. While POEM had lower rates of mucosal perforations and hiatal stenosis compared to LHM, LHM had higher rates of reflux esophagitis[10,8].

APPROACHES TO MYOTOMY

The choice between anterior and posterior approaches to myotomy in POEM remains a subject of debate. While Tan et al's randomized controlled trial found comparable efficacy and safety between the two approaches[12], Stavropoulos et al's study associated anterior POEM with more mucosal heat injuries and slower procedural times[13]. The posterior approach may offer advantages in safety and efficiency due to its better visualization of esophageal anatomy and reduced proximity to vital structures[11,12].

In younger patients with achalasia undergoing POEM, careful consideration is warranted due to concerns about post-procedure GERD and the long-term impact of anatomical changes induced by POEM. Despite obesity being a known risk factor for GERD, recent evidence suggests similar outcomes between obese and non-obese patients.

AES RELATED TO SEDATION DURING AND AFTER POEM

POEM should be performed under general anesthesia. AEs occurring under general anesthesia compared to sedation were lower, based on Bang et al[2]. During the POEM procedure, gas insufflation is vital for creating a submucosal tunnel and ensuring proper visualization. Anesthesiologists closely monitor capnography to manage increases in end-tidal CO₂ (etCO₂), aiming to maintain etCO₂ below 45 mmHg[2]. Additionally, vigilance over peak inspiratory pressure (pmax) is crucial, as it can indicate elevated intra-abdominal pressure, potentially requiring percutaneous abdominal needle decompression during pneumoperitoneum. Preventing aspiration is paramount during anesthesia induction for achalasia patients undergoing POEM. Physiological changes, such as increased mean arterial pressure and heart rate, are akin to those observed during laparoscopic surgery. Physiological changes induced by pneumoperitoneum, such as inferior vena cava compression and decreased cardiac output, pose risks, particularly in volume-depleted patients. Elevated pmax during POEM can result from factors like gastric distension or pneumoperitoneum, leading to lung injury. Subcutaneous emphysema is a common adverse event related to gas insufflation during POEM. Increased abdominal pressure, indicated by clinical signs such as tympanic percussion sounds, abdominal distension, and elevated pmax, adversely affects pulmonary mechanics, venous return to the heart, and visceral organ perfusion. Effective postoperative pain control is essential for POEM due to the significant postoperative pain it entails. However, general anesthesia or opioid use for pain control can lead to postoperative nausea and vomiting, potentially causing bleeding and damage to the surgical site if occurring immediately after the procedure[2].

CORRELATION BETWEEN SEVERE AES AND POEM/ENDOSCOPIC AND LAPAROSCOPIC APPROACHES IN ADULT ACHALASIA PATIENTS

In a systematic review and meta-analysis conducted by Niño-Ramírez et al[4], data from studies involving 1276 patients undergoing POEM, 5492 undergoing LHM, and 10346 undergoing endoscopic ballon dilatation (EBD) were analyzed. However, only a quarter of the studies included detailed reports of AEs related to the interventions. The reported proportions of AEs varied significantly, ranging from 0% to 27%[4].

Specifically, adverse events occurred at the following rates: 3.6% for POEM, 4.9% for LHM, and 3.1% for EBD. The occurrence of serious AEs showed similar associations in the LHM and POEM groups, as well as in the LHM and EBD groups. Mortality data at 30 days were only reported in three publications, revealing mortality rates of 0.09% for LHM and 1.4% for EBD, with insufficient information available for establishing an association with POEM. Overall, our findings indicate a proportion of serious AEs below 5% across all three techniques, with no significant discrepancies among them. The literature is predominantly composed of retrospective cohorts, posing a high risk for biases and rendering the available information insufficient for establishing comprehensive safety profiles. Furthermore, there is a lack of standardization in reporting AEs within clinical trial methodologies. Clear identification of AEs with the same methodological rigor employed in assessing efficacy is imperative[4].

ESOPHAGEAL LEAKAGE AFTER POEM

In a study conducted by Zhang et al[3], chest CT scans conducted on the 1^st day after POEM revealed postoperative esophageal leakage in three out of 476 patients (70.1%). The diagnosis of esophageal leakage relies on recognizing clinical symptoms such as chest pain, persistent high fever, or dyspnea, and confirming its presence through endoscopic examination. Esophageal leakage is a serious complication of esophageal surgery, with reported incidence ranging from 4% to 30%. However, the incidence after POEM is comparatively lower, with the current study reporting a 0.4% occurrence[3]. This lower incidence can be attributed to the preservation of the esophagus' surrounding structure and blood supply during the POEM procedure. Esophageal leakage predisposes patients to localized infections and systemic sepsis. In the observed cases, manifestations of infection emerged in the initial postoperative days, including fever, chest or upper abdominal pain, elevated white blood cell count, and pneumonia as evidenced by CT scans. Patients with leakage are susceptible to various infections, such as pneumonia, phlebitis, urinary tract infections, and wound infections, exacerbating their condition and complicating recovery[3].

DISTINCTION BETWEEN POST-POEM ALTERATIONS AND POEM COMPLICATIONS AIDED BY COMPUTED TOMOGRAPHY

Yang et al[7] assessed whether pneumomediastinum/pneumoperitoneum should be considered a typical postoperative observation after POEM, or if it indicates a complication. Some of the immediate changes following POEM may not have significant clinical implications, but others could indicate more serious issues. Determining whether pneumomediastinum/pneumoperitoneum is a typical post-POEM occurrence or a sign of complications requires thorough evaluation. Radiologists need to be well-acquainted with these CT findings to accurately interpret post-POEM scans. In a study by Inoue et al[14], CT scans conducted immediately after POEM showed a minor presence of CO₂ in the paraesophageal mediastinum for all patients. Interestingly, this finding did not result in any noticeable clinical effects or symptoms during follow-up examinations[7,13].

Similarly, Von Renteln et al[15] found that occurrences of pneumoperitoneum and subcutaneous emphysema following POEM did not lead to infectious complications such as mediastinitis or peritonitis. However, Von Renteln et al[15] emphasized the importance of promptly addressing any complications arising during or after POEM, which can often be effectively managed with conventional treatment methods. In this specific study, the authors suggested that complications might have been attributed to the use of room air during the procedure instead of CO₂. CO₂ is known to be more readily absorbed and significantly more soluble in serum compared to room air[7,14]. Notably, pneumoperitoneum has been reported as a common postoperative occurrence following laparoscopic surgery involving CO₂ insufflation, while pneumomediastinum has been observed as clinically benign after esophageal endoscopic submucosal dissection with CO₂ insufflation. All patients underwent a chest CT scan within the 1^st day following POEM (median: 22 hours; range: 16–30 hours). Post-treatment CT revealed various abnormalities, including pneumomediastinum (37.0%, 40/108), pneumoperitoneum (43.5%, 47/108), pneumothorax (0.9%, 1/108), subcutaneous emphysema (29.6%, 32/108), pleural effusion (69.4%, 75/108), segmental atelectasis of lungs (29.6%, 32/108), minor inflammation of the lungs (67.5%, 73/108), and ascites (0.9%, 1/108). Twenty-nine cases presented both pneumomediastinum and pneumoperitoneum, totaling a detection rate of 53.7% (58/108). The proportions of pneumomediastinum/pneumoperitoneum grades on CT were as follows: (1) Grade 0 (46.3%); (2) Grade I (38.9%); (3) Grade II (7.4%); and (4) Grade III (7.4%). The mean hospitalization duration was 4.3 days ± 3.3 days. Only three patients experienced severe complications, while 86 patients had mild complications. Severe complications included delayed hemorrhage, esophageal perforation treated endoscopically, and retroperitoneal abscess with ascites, which required specific interventions. No deaths were recorded. The presence of pneumomediastinum and/or pneumoperitoneum on CT did not significantly correlate with the development of complications, nor did it show a trend toward severe complications. Our study demonstrated a relatively high incidence (53.7%) of pneumomediastinum and/or pneumoperitoneum post-POEM, with severe complications occurring in only 2.8% (3/108) of cases[15]. Notably, the presence of these abnormalities on CT did not necessarily indicate severe complications. Moderate pleural effusion or ascites may serve as predictive indicators for severe complications post-POEM. Thus, pneumomediastinum and/or pneumoperitoneum detected by CT after POEM should not automatically be considered signs of complications[7,15].

COMPLICATIONS DURING AND AFTER PERORAL ENDOSCOPIC MYOTOMY

In a review conducted by Nabi et al[16] regarding AEs during and after peroral endoscopic myotomy, findings included insufflation-related AEs, commonly observed during the POEM procedure and include subcutaneous emphysema (7.5%), pneumothorax (1.2%), pneumomediastinum (1.1%), and pneumoperitoneum (6.8%)[16]. The incidence of these gas-related events varies across studies due to differences in AEs definitions, insufflation gas used (air or CO₂), and diagnostic modalities employed. The use of air instead of CO₂ has led to higher occurrences of gas-related AEs in some studies. For instance, one study reported pneumomediastinum (48%), pneumoperitoneum (37%), subcutaneous emphysema (28%), and pneumothorax (17%) when air was used in 52% of patients[16]. Because CO₂ is more readily absorbed, it is associated with lower incidence rates of gas-related events. Diagnosing gas-related AEs relies on clinical examination, ventilation parameters, and fluoroscopy. Management depends on the affected compartment and presence of hemodynamic disturbances. Indications for intervention include clinically significant abdominal distension and abnormal ventilation parameters. Capnopericardium, though rare, has been reported during POEM procedures. Early detection is crucial, as delayed management can lead to severe complications such as tension pneumopericardium.

Mucosal injuries are significant perioperative AEs, occurring in about 4.8% of cases. They range from minor discoloration to perforation, with risk factors including unhealthy esophageal mucosa, inadequate submucosal injections, and cases performed during the learning curve. Bleeding during POEM is typically minor, with major bleeding requiring intervention being rare (0%-1%). Delayed bleeding, occurring within 48 hours to 72 hours post-POEM, is also uncommon but requires attention. Postoperative pain is common but usually mild to moderate, while aspiration during POEM is rare (< 0.1%). Predictors of AEs include learning curve progression, insufflation gas choice, mucosal edema, and anatomical factors. Developing a standardized AE classification system is essential for uniform reporting and comparison across studies[16].

TRANSORAL INCISIONLESS FUNDOPLICATION AS AN ALTERNATIVE TO LONG-TERM PPI THERAPY FOR POST-POEM GERD

In a prospective pilot study by Ayoub et al[17] POEM was an effective first-line treatment for achalasia. However, post-POEM GERD is a common issue, occurring at rates at least double those observed after surgical myotomy. While proton pump inhibitors (PPIs) are effective for managing GERD, long-term adherence is often difficult, prompting interest in alternative treatments. Transoral incisionless fundoplication (TIF) has emerged as a minimally invasive option for managing GERD, particularly in patients with small or no hiatal hernias. In the study, 40% of patients with objective evidence of post-POEM GERD opted for TIF, and 75% were able to significantly reduce or discontinue PPI therapy. TIF was safe, well-tolerated, and resulted in significant improvements in GERD symptoms, making it a promising alternative to long-term PPI use. This is the first patient-driven study of post-POEM GERD management, systematically offering TIF as an option. The incidence of GERD after POEM is notable, with 39%-58% of patients showing abnormal acid exposure. In our study, 52% of patients had abnormal acid exposure, consistent with other reports. While PPI therapy is commonly used, some patients prefer alternatives, and TIF offers a minimally invasive solution. Our findings align with other studies, showing that TIF effectively reduces or eliminates PPIs use in many patients. Post-POEM GERD is thought to result from factors like loss of lower esophageal sphincter tone and changes in the Angle of His. TIF helps restore the gastroesophageal flap valve function, though some patients may still experience residual GERD. Our study is the first to prospectively evaluate TIF as an alternative to long-term PPIs in post-POEM GERD patients, with positive results. Further studies with objective monitoring, including potential of hydrogen testing, are needed to confirm these findings and assess the long-term benefits of TIF.

CONCLUSION

In conclusion, POEM has revolutionized the treatment of achalasia and other UGT motility disorders, offering effective and minimally invasive solutions. While POEM has shown strong clinical outcomes with low complication rates, challenges remain, particularly in optimizing procedural precision, managing post-operative GERD, and addressing complications such as mucosal injuries, gas-related events, and esophageal leakage. The procedure's safety profile continues to improve with advances in technique, anesthesia, and interdisciplinary collaboration. However, post-POEM GERD remains a significant concern, and alternative treatments like TIF have shown promise in reducing the need for long-term PPIs. Future research, including more rigorous clinical trials and standardized adverse event reporting, is needed to further refine POEM's safety and efficacy, ensuring it remains a leading treatment option for achalasia and beyond.