AIM: To assess the safety and feasibility of peroral esophageal myotomy (POEM) in patients with achalasia.

METHODS: From January 2012 to March 2014, 50 patients (28 men, 22 women; mean age: 42.8 years, range: 14-70 years) underwent POEM. Pre- and postoperative symptoms were quantified using the Eckardt scoring system. Barium swallow and esophagogastroscopy were performed before and after POEM, respectively. Esophageal motility was evaluated in all patients, both preoperatively and one month after POEM treatment, using a high-resolution manometry system. Manometry data, Eckardt scores, lower esophageal sphincter pressure and barium swallow results were used to evaluate the effect of the procedure.

RESULTS: POEM was successfully completed for all patients. The mean procedure time was 55.4 ± 17.3 min and the mean total length of myotomy of the circular esophagus was 10.5 ± 2.6 cm. No specific complications occurred, with the exception of two patients that developed asymptomatic pneumomediastinum and subcutaneous emphysema. Clinical improvement in symptoms was achieved in all patients. Approximately 77.5% of patients experienced weight gain 6 mo after POEM, with an average of 4.78 kg (range: 2-15 kg). The lower esophageal sphincter resting pressure, four second integrated relaxation pressure and Eckardt scores were all significantly reduced after POEM (Ps < 0.05). A small segment of proximal esophageal peristalsis appeared postoperatively in two patients, but without normal esophageal peristalsis. The average diameter of the esophageal lumen decreased significantly from 4.39 to 3.09 cm (P < 0.01).

CONCLUSION: POEM can relieve achalasia symptoms, improve gastroesophageal junction relaxation and restore esophageal body motility function, but not normal esophageal peristalsis.

Achalasia is an esophageal motility disorder of unknown etiology, characterized by the aperistalsis of the distal esophagus and defective relaxation of the lower esophageal sphincter (LES)[1,2]. Although achalasia is rare, recent reports suggest an increasing incidence, with rates of up to 16 per 1000000 per year in some populations, mainly in South America and Europe[3,4]. Clinical symptoms of achalasia include dysphagia, retrosternal pain and the regurgitation of undigested food. The diagnosis of achalasia is made on the basis of symptoms, results of a barium esophagram and endoscopy, as well as esophageal manometry, which is the gold standard. This type of high-resolution manometry (HRM) has demonstrated an increased diagnostic accuracy and yield of achalasia patients compared to traditional methods of diagnosis[5,6].

Although the pathophysiology of achalasia remains largely unknown[5], it has a low mortality rate. However, achalasia is a chronic disorder that severely affects patient quality of life. Endoscopic and surgical therapies focus on relaxation or mechanical disruption of the LES. However, these methods are inefficient, with a high degree of temporary relapse and complications, such as bleeding and perforation[7,8]. Recently, a novel endoscopic technique called peroral endoscopic myotomy (POEM) was developed as a treatment for achalasia treatment[9]. This technique is based on natural orifice transluminal endoscopic surgery[10], in which surgical instruments, and often a camera, are passed through existing openings in the body to avoid scarring and potential complications of invasive surgery. However, the outcomes for POEM need to be critically assessed by clinical studies. Therefore, the aim of this paper was to describe the use of POEM for treating achalasia patients and to evaluate its efficacy via high-resolution manometry (HRM), validated Eckardt symptom scores, esophagogastroscopy and barium swallow.

From January 2012 to March 2014, POEM was successfully performed in 50 patients with achalasia. The demographic information and clinical characteristics of all enrolled patients are presented in Table 1. None of the patients showed signs of other unrelated diseases.

The duration of the POEM procedures ranged from 30 to 120 min, with an average time of 55.4 ± 17.3 min. The dentate line was a mean of 43.4 (36.0-55.0) cm from the incision, the submucosal tunnel was a mean length of 13.5 (8.0-23.0) cm and circular myotomy was 10.5 (3.0-19.0) cm. During the procedure, the entry site within the submucosal tunnel was closed with 2-15 hemostatic clips. No instances of major bleeding occurred intra- or postoperatively. Furthermore, there were no serious complications related to POEM. Mild chest pain appeared in most patients after 7-14 d, which ultimately subsided without additional treatment. A small amount of postoperative asymptomatic pneumomediastinum and subcutaneous emphysema occurred in 2/50 (4%) patients, which resolved after one week.

Patients were followed-up for a mean of 7.25 mo. Thirty-six patients completed 6 mo of postoperative treatment and 12 cases were followed up for > 1 year (Figure 2). POEM was successful in almost all (49/50; 98%) cases, as determined by patient assessment at a 1 mo follow-up exam; one patient had an Eckardt score of 5 (preoperative Eckardt: 11) and unimproved LESP (13.2 mmHg vs 26.0 mmHg, pre- and postoperative, respectively) by HRM, indicating relapse. This patient was then treated with endoscopic balloon dilation (EBD), which reduced the Eckardt score to 2, a score that was maintained for the remainder of the study. Another patient relapsed 2 mo after POEM, presenting with a solid swallowing obstruction for which EBD was requested, which restored the Eckardt score to 1. An additional five cases that did not meet the score of recurrence required supplementary treatment with EBD after POEM for slight discomfort.

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Figure 2 Eckardt scores. The Eckardt scores of patients were recorded before peroral endoscopic myotomy and at various times postoperatively; P < 0.01 vs before peroral endoscopic myotomy.

Pre- and postoperative results were available for 35/50 patients, with three patients failing to undergo HRM due to the high pressure within the LES. One month after POEM, LESP and 4sIRP were significantly decreased and LESRR was significantly increased in liquid swallows compared to baseline values (all Ps < 0.01) (Table 2). Representative HRM results are shown in Figure 3. The change in Eckardt score was correlated with the decrease in LESP and 4sIRP (Ps < 0.05), but not with LESP. Interestingly, two patients exhibited a small segment of proximal esophageal peristalsis at postoperative examinations, but normal esophageal peristaltic function was not completely restored.

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Figure 3 Esophageal high-resolution manometry. Representative manometric results from a patient with type II achalasia A: Before; and B: One month after peroral endoscopic myotomy. Lower esophageal sphincter pressure was reduced, with relaxation and passage of lower esophageal sphincter seen upon swallowing.

One month after POEM, substantially improved emptying from the esophagus to the EGJ could be observed by a barium swallow (Figure 4). The average esophageal diameter at its widest changed from 4.4 (2.5-8.5) to 3.1 (2.0-7.0) cm. After 6 mo of follow-up, the mean diameter was 3.0 (1.7-7.0) cm, with no retention of barium in the esophagus. The 2 mo postoperative assessment using upper gastrointestinal endoscopy showed that the esophageal mucosal incisions healed well and the endoscopes could pass through the cardiae smoothly, without any signs of esophagitis. Six months after POEM treatment, approximately 77.5% of patients had gained an average of 4.8 (2.0-15.0) kg. There were no reports of reflux symptoms or specific complications during any of the postoperative follow-up assessments (Table 3).

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Figure 4 Barium swallow. A: Dilated esophagus showing a retained column of barium and “bird’s beak”, suggestive of achalasia; B: Esophagogram one month after peroral endoscopic myotomy. Barium passed and was excreted quickly through the lower esophageal sphincter.

As there is no cure for achalasia, most therapeutic strategies aim to alleviate symptoms by reducing LESP and relieving esophageal obstruction. Traditional treatments for achalasia include medications, EBD, endoscopic botulinum toxin injection and surgical myotomy, all of which have various advantages and drawbacks[5,15-18]. Natural orifice transluminal endoscopic surgery is gaining attention because it is minimally invasive and results in little to no visible scarring. POEM is a related technique that was first described by Pasricha et al[19] in 2007, who performed a myotomy via the esophageal lumen in a porcine model of achalasia. Three years later, Inoue et al[9] demonstrated its effectiveness in relieving achalasia symptoms in human patients, generating fewer traumas and less complications and allowing for rapid recovery.

A number of recent Chinese studies on POEM have been reported, which have focused on the evaluation of its effectiveness[20], patient criteria for treatment[21], management of complications[22], length and location of entry incision[23] and the comparison with other types of surgery, including Heller myotomy[24]. In this study, all patients successfully underwent POEM without reflux symptoms or serious complications and with significantly improved Eckardt scores. There was a 100% (50/50) instant remission rate after surgery and a 96% (48/50) symptom remission rate after six months. This rate of symptomatic relief with POEM is considered high and is in line with previous reports[25,26]. The observed symptom recurrence may have been due to insufficient incision length of the esophageal circular muscle. Supplementary treatment with EBD in seven cases demonstrates the feasibility and safety of POEM. Moreover, 20% of our patients had received prior treatment, demonstrating that POEM can be performed efficiently and safely in recurrent cases. Although some studies have shown that prior therapies (such as EBD or endoscopic botulinum toxin injection) can make the operation more difficult and diminish the outcome[27,28], we found no influence of prior treatment regimens on the ultimate success rate of POEM in treating achalasia, in agreement with other reports[29,30]. Taken together, these results demonstrate that POEM is a suitable treatment option for achalasia patients with various disease stages.

The manometry results show a clear improvement on EGJ relaxation, as evidenced by the significant decrease in LESP and 4sIRP after POEM treatment. Furthermore, the 4sIRP reduction correlates with the decrease in Eckardt score, which is consistent with previous reports[31]. As such, these assessments could be used as a positive predictor before treatment. Furthermore, 4sIRP is a quantifiable method of distinguishing impaired LES relaxation in achalasia from that of a healthy individual[32]. In addition, while the decrease in LESRR is thought to result from the failure of LES relaxation, this measure rises after intervention and has been a continuing issue of debate in achalasia studies[33].

To the best of our knowledge, normal driving esophageal peristalsis cannot be restored by POEM in achalasia patients[34]. Nevertheless, there are several studies showing that some patients can recover a certain level of peristalsis after intervention[35]. A small segment of proximal esophageal peristalsis was recovered in two patients in our study. These peristaltic changes may be explained by a higher accuracy of measurement achieved using the manometry catheter, the narrowing of the dilated esophagus after POEM, or the varying levels in impairment of esophageal inhibitory neurons. If these neurons are damaged beyond repair, it is unlikely that POEM is sufficient to completely restore normal peristaltic function. Thus, POEM cannot completely restore normal esophageal peristalsis, but can improve esophageal body motility and EGJ relaxation.

Our study has several limitations. First, the follow-up assessment period was only one year post-procedure and some patients may show symptom relapse or develop long-term complications. Therefore, a longer-term follow-up study is required to assess the efficacy and safety of this novel treatment method for achalasia. Furthermore, this study is based on a small sample size and the number of each subtype of cases is limited. As POEM is still a relatively new technique, large-scale and/or multicenter studies are needed to fully demonstrate its benefits. Lastly, this was a retrospective study, which has a larger bias than a prospective study. The reliability of its outcomes is directly affected by the integrity and authenticity of collected data. Therefore, there is a need for a randomized controlled trial with long-term follow-up.

In conclusion, POEM is a promising, feasible and safe treatment option for patients with achalasia. This technique demonstrates substantial short-term therapeutic effectiveness, with relief of achalasia symptoms, improved EGJ relaxation and restoration of a certain degree of esophageal body motility function, although normal esophageal peristalsis was not obtained. Importantly, POEM is still in its initial stages of development and further modifications will likely improve the overall benefits. Long-term follow-ups are still needed to thoroughly assess its effectiveness compared with other therapies for the management of achalasia.