The 2 years’ long-term efficacy and safety of peroral endoscopic myotomy for the treatment of achalasia: a systematic review

Achalasia is characterized by aperistalsis of the esophagus and impaired relaxation of the lower esophageal sphincter [1, 2]. Pathologic mechanisms of achalasia remain unknown, although various studies have reported that virus, inflammation, and autoimmune mechanisms may affect the neuronal degeneration of esophageal ganglion cells [1]. Patients with achalasia have typical clinical manifestations, including dysphagia, retrosternal pain, reflux, heartburn, and weight loss [3‐5].

The development of medical technology and equipment has led to a breakthrough in the treatment of achalasia. Initial interventions included drug therapy, endoscopic balloon dilatation (EBD), botulinum toxin injections (BTI), and laparoscopic Heller myotomy (LHM). For nearly 100 years, the surgical approach to achalasia was based on an open Heller procedure. However, over the last 20 years, LHM has become a routinely performed procedure, with obvious advantages compared with the open approach [1]. However, each of these interventions has both advantages and disadvantages. The effectiveness of drug treatment is shorter and the recurrence rate is higher. To ensure its effectiveness, BTI should be used for repeated treatment. Likewise, EBD may require repeated treatments, and LHM often requires an additional fundoplication procedure to reduce the occurrence of gastroesophageal reflux disease [5, 6]. Endoscopic myotomy for achalasia was first reported by Ortega et al. in 1980 [7]. Pasricha et al. reported peroral endoscopic myotomy (POEM) procedures in animal models of pigs in 2007 [8]. Inoue et al. reported the feasibility and effectiveness of POEM in 2010 [9]. Since then, POEM has been widely performed, and several studies have reported its long-term efficacy and safety [10, 12, 13]. Therefore, our systematic review was designed to explore the 2 years’ long-term effectiveness and safety of POEM.

The treatment of achalasia has advanced over the decades, expanding from drug therapies to include modalities such as endoscopic balloon dilation, botulinum toxin injection, and LHM. The treatment of achalasia has gradually transformed from invasive to minimally invasive. The goals of therapy include decreasing the Eckardt score, reducing LESP, improving esophageal emptying, and relieving symptoms [23‐26]. With the advancement of endoscopic devices and techniques, a novel minimal invasive treatment approach, POEM has been developed for treating achalasia [7‐9, 27]. Presently, several researchers have reported the effectiveness and safety of POEM. von Renteln et al. reported that the sustained clinical success rate was 82.4% in patients with follow-up period of > 1 year [22]. The efficiency of POEM was reported to be 82–100% by the White Paper Committee et al. in 2014 [30]. Inoue et al. reported the long-term effective rate of 88.5% in 2015 [31]. Youn et al., in their study with follow-up period of > 1 year, reported a range of efficiency of 82.4–100% [10]. However, no prior reviews or meta-analyses have reported the efficacy of POEM with long-term follow-up. Different from the previous systematic reviews, we explored the long-term outcome (median or mean follow-up period of > 2 years) of POEM for achalasia. In our review, the overall mean follow-up period was 30.0 months. Based on our analysis, we found a high overall clinical success rate of 92.9% for POEM, which was similar to the results of previous studies (e.g., White Paper Committee [30] and Youn [10]).

Before the introduction of POEM, LHM was considered an effective method for the treatment of achalasia [1, 28, 29]. During a short follow-up period, some studies have reported that POEM had similar efficacy and safety as LHM [13, 32, 38]. In the study by Peng et al. [13], no significant difference was observed in the myotomy length between POEM and LHM. Improvement in the quality of life after POEM was similar to that after LHM. They demonstrate that the myotomy length was similar between LHM and POEM. However, compared with LHM, POEM may has several obvious advantages, including (i) shorter operation duration; (ii) shorter length of hospital stay; (iii) lower incidence of postoperative complications and higher success rate; (iv) milder postoperative pain; and (v) lower rates of GER and RE [13, 32‐38].

Our study indicated that the overall average length of myotomy was 9.3 cm. In recent years, it has become a hot topic about whether long or short muscle incision should be used to treat achalasia. It has been reported that these two therapies had similar success rate and complication rate. However, the operation time of short myotomy was less obviously [39, 40]. In the future, a large number of conclusive studies are needed to assess the long-term outcomes of the short myotomy group versus long myotomy group.

Currently, a circular myotomy (CM) is a frequently used in POEM procedure. Li et al. and Duan et al. have reported a comparison between circular and full-thickness myotomy (FTM). In their studies, the average procedure duration was shorter for FTM than for CM [19, 41]. The study by Li et al. demonstrated that the short-term efficacy and safety were similar between FTM and CM [41]. Duan et al. reported that FTM might increase the incidence of GERD or RE [19]. So, further studies are needed to evaluate the long-term results of FTM versus CM.

Although a few studies reported that the complication rate was 0–30% [1, 6, 42, 43], severe complications of POEM have not been reported. The study by Crespin et al. indicated that the incidence of GERD or RE was 0–19% [1]. Our review demonstrated that the overall incidence of complications was 21.2% and that of GERD/RE was 10.2% during the 2-years’ follow-up. All these adverse events can be alleviated by conservative treatment.

Our review has some limitations. The results of our summary and analysis might have a selection bias because most of our analysis samples came from Asia and from a single endoscopy center. The sample size of the analysis was also relatively small. Large sample and multi-center studies are needed to clarify the effectiveness and safety of POEM.

Our systematic review examined 10 studies about POEM for achalasia. We found that POEM is effective and safe for the treatment of achalasia during the 2 years’ long-term follow-up duration. Further randomized controlled trial comparing POEM with other treatment modalities with large sample size are wrranted in future.