The Treatment of Esophageal Achalasia: At the Intersection Between Innovation and Patient's Care

During the 1970s and 1980s pneumatic dilatation (PD) was the primary treatment modality for esophageal achalasia, whereas a surgical myotomy (transabdominal or transthoracic) was relegated to the treatment of patients who suffered a mucosal perforation during PD or developed recurrent symptoms after multiple dilatations. ¹ Minimally invasive surgery for esophageal achalasia in the United States was first introduced in 1991 at the University of California San Francisco. ² A Heller myotomy was performed through a left thoracoscopic approach thoracoscopic Heller myotomy (THM) without an antireflux procedure; the myotomy extended for 5 mm only onto the gastric wall with the goal of relieving dysphagia while avoiding postoperative gastroesophageal reflux. The initial experience showed that this technique clearly met the criteria of an effective innovation: it was feasible, safe, effective, and by avoiding a thoracotomy, it provided clear advantages to both patients and the health care system as it was associated with minimal postoperative discomfort, a shorter hospital stay, and a faster return to daily activities. ² These excellent results soon established THM as the primary treatment in most centers. The initial enthusiasm, however, was soon tempered by the finding that although 2/3 of patients were asymptomatic (no heartburn), 60% had pathologic reflux when tested by 24-hour pH monitoring. ² We then decided to adopt the technique used in Padua (Italy), performing a Heller myotomy through a laparoscopic approach with the addition of a Dor fundoplication laparoscopic Heller myotomy doz (LHMD). ³ When we compared the first 30 THM with the first 30 LHMD, we realized that although the relief of symptoms was similar and excellent, 60% of patients after THM but only 10% after LHMD experienced pathologic reflux when tested by pH monitoring. These results were later confirmed by a larger multicenter study combining the experience of University of California San Francisco and the University of Washington in Seattle. ⁴ Thirty-five patients who had a THM were compared with 133 patients who had an LHMD. The improvement of dysphagia was similar and excellent in both groups, but the incidence of postoperative reflux was 60% after THM but 17% only after LHMD.

A randomized trial was eventually performed by Richards et al., and confirmed the importance of adding an antireflux operation after the laparoscopic Heller myotomy (LHM). ⁵ Pathologic reflux (by pH monitoring) was present in 10 of 21 patients (47.6%) after laparoscopic Heller myotomy, but in only 2 of 22 patients (9.1%) after Heller plus Dor. The evolution of the approach, from thoracoscopic to laparoscopic with the addition of a partial fundoplication clearly struck a very effective balance, resolving dysphagia while avoiding pathologic reflux in most patients.

It is important to stress the importance of these findings. The cause of esophageal achalasia is unknown, and any form of treatment provides palliation by eliminating the outflow obstruction caused by a nonrelaxing and often hypertensive lower esophageal sphincter (LES). However, as in achalasia there is no esophageal peristalsis, once the muscle fibers of LES are either ruptured (PD) or cut (LHM or per oral endoscopic myotomy [POEM]), reflux tends to occur in the majority of patients, and because of the slow clearance there is damage to the esophageal mucosa due to prolonged contact time with the gastric refluxate. Surgeons, but not gastroenterologists, soon accepted the fact that it was critical to avoid postoperative reflux for the fear of developing over the years either peptic strictures (common cause of recurrent symptoms), or Barrett's esophagus and adenocarcinoma. Therefore, for many years the LHM with a partial fundoplication was the primary form of treatment in the United States and abroad, as long-term follow-up showed excellent and durable results. ⁶ In addition, and contrary to PD, there was a very low need for re-treatment. ⁷ A recent review of 1001 patients who underwent an LHMD at the University of Padua between 1992 and 2017, showed a success rate at 5 years of 89.5%, with a probability of being symptom free at 20 years of 80% ⁸ : pH monitoring showed pathologic reflux in 9.1% of patients only. Therefore, time has shown that the LHM is safe, effective, and able to provide major benefits to both patients and the health care system.

In 2010, Dr. Inoue from Japan published the initial results in 17 achalasia patients treated with a novel endoscopic technique—POEM. By creating a submucosal esophageal tunnel, he was able to cut the muscle fibers of the distal esophagus and proximal stomach for a total length of about 8 cm. The dysphagia score decreased from 10 to 1.3 and only 1 patient experienced heartburn, which was treated with proton pump inhibitors. ⁹ These excellent results in terms of relief of dysphagia were later confirmed by Swanstrom et al., who first reported in the United States the outcome of POEM in 18 patients, with relief of dysphagia in all (Eckardt score <1). However, for the first time reflux was objectively studied, and esophagogastroduodenoscopy showed esophagitis in 28% of patients while pH monitoring showed pathologic reflux in 46% of them. ¹⁰ After these initial studies, this technique was soon adopted across the world, and embraced by both gastroenterologists and surgeons. For instance, in 2016 Familiari et al. from the Catholic University in Rome, Italy, reported at a median follow-up of 11 months a success rate of 94.5% among 94 achalasia patients. ¹¹ When studied by pH monitoring, 53% of patients had pathologic reflux. Similarly, a multicenter study that included 282 patients showed a rate of pathologic reflux after POEM of 57.8% at a mean follow-up of 12 months. ¹² Jones et al. performed POEM in 43 achalasia patients. At a mean follow-up of 6 months, all patients had relief of dysphagia, but 58% showed pathologic reflux when tested by pH monitoring. ¹³ Interestingly, symptoms and quality of life did not differ between patients with normal and those with abnormal esophageal acid exposure, suggesting that only objective testing can detect patients who have developed reflux and are in need for treatment.

In a recent meta-analysis, Schlottmann et al. summarized the available data on POEM, and a compared POEM with LHM with partial fundoplication. ¹⁴ This study showed that POEM was slightly more effective than LHM, although with a much shorter follow-up (success rate: 93% POEM—88% LHM). Although the incidence of reflux symptoms was similar between the two procedures (19% POEM–17% LHM), a significant difference was found in the rate of endoscopic esophagitis (22% POEM–12% LHM), and in the presence of pathologic reflux by pH monitoring (48% POEM–11% LHM).

Initially, this very high rate of pathologic reflux was dismissed by the proponents of POEM, who suggested that treatment of PPIs for the patients experiencing heartburn was all that was needed. However, mounting evidence suggests that this approach has many pitfalls:

Proton pump inhibitors just block acid production by the parietal cells but do not block reflux through an incompetent LES.

More and more patients are reluctant to take PPI for a long time because of the known side effects, including now interstitial nephritis and cardiac events in addition to C. difficile infection, osteoporosis, and pneumonia. ¹⁵

In a large study of 331 achalasia patients treated by PD, at a mean follow-up of 8.9 years, 8.4% were diagnosed with Barrett's esophagus. Barrett's esophagus was more frequent (28.4%) among patients who had achalasia and a hiatal hernia. ¹⁶ A multicenter analysis of 80 patients who had POEM followed for an average of 29 months, showed that 1 patient developed a reflux stricture and 3 patients Barrett's esophagus. In addition, the success rate was initially 93.7% but decreased to 78.5% over time. ¹⁷

Finally, the first case of Barrett cancer after POEM has been recently reported. ¹⁸

So, how do we summarize what is known about POEM? It is an interesting endoscopic technique, with an excellent safety profile, that provides very good relief symptoms while avoiding scars. It is particularly valuable in patients with type III achalasia, ¹⁹ and to treat recurrent symptoms after LHM. ²⁰ However, it is important to underline that at the present time any comparison with the LHM does not make any sense, as in general the follow-up in most studies is very short or incomplete. For instance, Perbtani et al. recently described the “long-term outcomes and quality of life” after POEM, but the follow-up was 16.4 months only. ²¹ Inoue, the main promoter of POEM, recently reported a series of 500 patients, but the 3-year data were based on the follow-up of 61/500 patients only (12.2%), therefore making any conclusion irrelevant. ²²

As stressed by Dr. Richter in a commentary to the study of Perbtani et al., “the real elephant in the room” is the high rate of post-POEM reflux. ²³ This rate is probably higher in the United States and in Europe as compared with Asia, as Asian patients have a lower body mass index and a high rate of Helicobacter pylori with low acid secretion. Because of these concerns, and the fact that post-POEM patients with pathologic reflux are often asymptomatic, every patient should be carefully advised before treatment, stressing the probability of developing reflux after POEM, the need for objective testing such as endoscopy and pH monitoring, and for possible medical or surgical therapy.

Along these lines, it seems unethical to perform POEM as primary treatment in children with achalasia. In a recent report, Nabi et al. described the outcome of POEM among 44 children with a mean age of 14 years. ²⁴ At 4 year follow-up, although the success rate was 83%, 55% of patients had erosive esophagitis and 54% pathologic reflux by pH monitoring (not all patients had pH monitoring).

In conclusion, POEM is a new technique in the armamentarium of the treatment of esophageal achalasia. Although it has been shown to be the preferred treatment for type III achalasia and for recurrent symptoms after LHM, it might not be the best initial treatment for most patients with esophageal achalasia, particularly if they are young. Longer follow-up time and prospective and randomized trial between POEM and LHM will give the answer.

The story of the treatment of esophageal achalasia reminds us of the words of George Santayana “Those who do not remember the past are condemned to repeat it.” ²⁵