Esophageal achalasia is an esophageal motility disorder of unknown etiology [1,2,3]. The condition is characterized by failure of the lower esophageal sphincter (LES) to relax, along with impaired peristalsis of the esophageal body. Peroral endoscopic myotomy (POEM) is a novel, minimally invasive treatment for esophageal achalasia and related disorders, first reported by Inoue et al.; however, few subsequent reports have included more than 1000 patients [4, 5]. The purpose of our study was to retrospectively evaluate the results of POEM in a large patient cohort, and to verify the efficacy and safety of POEM.

Methods

We retrospectively analyzed data for patients undergoing POEM for esophageal achalasia at eight facilities in Japan between September 2008 and October 2015 (Table 1). All patients gave informed consent before undergoing POEM, and each institutional review board approved this study. The study met the Japanese governmental guidelines.

Table 1 The names of the eight facilities participating in this study
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Preoperative patient evaluation

Patients’ clinical achalasia symptoms were assessed using Eckardt scores [6]. The Eckardt scores comprises four components: dysphagia, chest pain, regurgitation, and weight loss. Each component is assigned a score from 0 to 3 based on the patient’s self-reported assessment, with a total score ranging from 0 to 12. A higher Eckardt score reflects more severe symptoms of achalasia, whereas a lower score postoperatively indicates improvement in symptoms. Preoperative tests included manometry, endoscopy, barium swallow examination, and computed tomography. The type of achalasia was determined according to the findings from barium swallow examination and computed tomography. Each patient’s systemic function was also evaluated to determine whether general anesthesia was possible.

POEM procedure

POEM was performed using the methods described by Inoue et al. (Fig. 1) [4, 7, 8]. All procedures were performed or supervised by surgeons from each of the eight study facilities who had learned the POEM procedure from Dr Inoue and who continued to use the same techniques. POEM was performed under general anesthesia with endotracheal intubation with patients in the supine position to be able to use preoperatively computed tomographic information. We used carbon dioxide exclusively to insufflate when using the endoscope. POEM was performed using a triangle-tip electrosurgical knife (KD-640L, Olympus, Tokyo, Japan).

Fig. 1
figure 1

POEM procedure (posterior myotomy), A mucosal entry, B creating submucosal tunnel (esophageal body), C creating submucosal tunnel (LES), D after creating submucosal tunnel, E after myotomy, F closure of mucosal entry

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Evaluation of the treatment effect

We evaluated patients’ results following POEM based on patient interviews, and endoscopy and manometry findings. We used patients’ Eckardt scores to evaluate the efficacy of POEM as follows: an Eckardt score ≦ 3 post-POEM was deemed a successful outcome. We assessed the safety of POEM using the Clavien–Dindo classification system to evaluate adverse events associated with the procedure [9]. For gastroesophageal reflux disease (GERD) after POEM, we evaluated the presence or absence of GERD, patients’ symptoms, and the degree of erosive esophagitis in endoscopy. Erosive esophagitis was evaluated according to the Los Angeles classification system [10].

Results

Patients’ demographics

POEM was performed in 1346 patients with achalasia (729 women and 617 men with a mean age of 47.2  ± 17.1 years) during the study period (Table 2). Achalasia was the straight type in 1105 (82%) patients and the sigmoid type in 241 (18%) patients; 381 (28%) patients had previously undergone pneumatic dilation, and 43 patients (3%) had previously undergone Heller–Dor operation.

Table 2 Patient’s demographics
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POEM outcomes

The efficacy of POEM within 6 months after surgery was 95.1% and 94.7% 1 year postoperatively (Table 3). POEM was successfully completed (technical success) in all patients, with a mean procedural time of 99.6  ±  41.7 min (Table 4). Anterior myotomy was performed in 901 patients (67%), and posterior myotomy was performed in 445 (33%) patients. The mean length of the esophageal myotomies was 10.8 ±  3.8 cm, while the mean length of the gastric myotomies was 2.8  ±  1.1 cm.

Table 3 Patient outcomes following peroral endoscopic myotomy
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Table 4 Details of the peroral endoscopic myotomy procedure
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Adverse events

Adverse events of Clavien–Dindo classification grade ≤ IIIa occurred in 50 patients (3.7%); five patients (0.4%) experienced mucosal perforation, 24 patients (1.8%) experienced mucosal injury without perforation, nine patients (0.7%) experienced submucosal hematoma, and two patients (0.1%) experienced major bleeding. There were no Clavien–Dindo classification grade ≥ IIIb adverse events.

GERD after POEM

Within 6 months after POEM, 1176 patients underwent endoscopic examination, and 63% had erosive esophagitis of Los Angeles classification grade A–D (Table 5). Severe erosive esophagitis (Los Angeles grade C or D) was observed in 6.2% of the patients. Symptomatic GERD was observed in 14.8% of patients; however, both erosive esophagitis and symptomatic GERD responded to treatment with a proton-pump inhibitor.

Table 5 Gastroesophageal reflux disease after peroral endoscopic myotomy
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Discussion

POEM is a novel, minimally invasive treatment for esophageal achalasia and related disorders that was first reported by Inoue et al. in 2010 [4]. Many facilities worldwide have reported the therapeutic efficacy of POEM, but few reports have included more than 1000 patients [11,12,13,14,15]. In this study, we retrospectively examined the treatment results for > 1300 patients undergoing POEM at eight facilities in Japan, and we verified the efficacy and safety of POEM within 6 months and 1 year postoperatively.

The technical success of POEM in this study was 100%, and the efficacy of POEM was approximately 95% within 6 months and 1 year after POEM. Adverse events occurred in approximately 4% of our patients, half of which were associated with mucosal injury, but no patients suffered Clavien–Dindo classification grade ≥ IIIb adverse effects requiring surgical treatment. There are several possible reasons for the high efficacy and safety in this study. First, most surgeons in this study learned the POEM procedure during at least 1 year of study from its originator, Dr Inoue, and used the techniques consistently, thereafter. Second, all procedures were performed by these trained surgeons or under their supervision.

Regarding GERD after POEM, erosive esophagitis was observed in 63% of our patients; however, esophagitis of Los Angeles classification grade C and D occurred in only 6% of the patients. Additionally, the erosive esophagitis was mild in most patients, and all patients responded to a proton-pump inhibitor. Symptomatic GERD was recognized in 15% of patients, which also responded to treatment with a proton-pump inhibitor, similar to previous reports. We evaluated GERD after POEM in more than 1000 patients in this study, and no patients suffered refractory GERD requiring additional fundoplication. However, some reports have described patients requiring fundoplication after POEM [16, 17]. Therefore, long-term follow-up and reports of the clinical outcomes for patients with GERD after POEM are needed. Moreover, the risk factors for severe GERD after POEM must be defined.

The limitations of this study are the retrospective design, the relatively short-term follow-up, and that we did not include patients with other esophageal motility disorders. In the future, we plan to address these limitations by completing a prospective study or a retrospective study with a higher number of facilities and examination criteria.

In conclusion, our multicenter retrospective study confirmed the safety and efficacy of POEM in a large patient series. Our results support POEM as the first-line and standard treatment for esophageal achalasia.