Pneumatic dilation or myotomy for achalasia?

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Vela MF, Richter JE, Khandwala F, Blackstone EH, Wachsberger D, Baker ME, Rice TW (Cleveland Clinic Foundation, Cleveland, OH). The long-term efficacy of pneumatic dilatation and Heller myotomy for the treatment of achalasia. Clin Gastroenterol Hepatol 2006;4:580–587.

Achalasia is a rare primary esophageal motility disorder of unknown etiology caused by degeneration of the inhibitory innervation of the esophagus, resulting in aperistalsis and failure of the lower esophageal sphincter (LES) to relax. (J Clin Gastroenterol 1988;27:21–35). The disease has an annual incidence of approximately 1 case per 100,000 (Gut 1992;33:1011–1105). Presenting symptoms may include heartburn and acid regurgitation not responding to proton pump inhibitor (PPI) therapy, progressive dysphagia to solids followed by liquids, chest pain, bland regurgitation, and weight loss. Treatment does not reverse the underlying peristalsis, but is designed to disrupt the elevated pressure of the LES to facilitate emptying from the distal esophagus. Although prior population-based studies suggested a 16-fold increase in squamous cell carcinoma of the esophagus in patients with achalasia (JAMA 1995;274:1359–1362), other series have noted no increased risk, particularly with early treatment of achalasia (Dig Dis Sci 1993;38:1920–1925). Disruption of the LES, however, can lead to gastroesophageal reflux and complications associated with gastroesophageal reflux disease (GERD), including erosive esophagitis and Barrett’s esophagus (Aliment Pharmacol Ther 2006;23:1197–1203). Long-term outcomes after treatment for achalasia have not been well defined. Although there is no cure for achalasia, the best treatment for palliation of symptoms remains in question, and long-term outcomes after therapy have not been well studied.

In this retrospective study from the Cleveland Clinic, 106 patients with achalasia treated between 1994 and 2002 with either pneumatic balloon dilation or laparoscopic Heller myotomy were studied to determine duration of therapy and risk factors for treatment failure. Diagnosis and assessment of achalasia was determined by esophageal manometry (abnormal LES relaxation and aperistalsis on 10 wet swallows), endoscopy to exclude malignancy, and timed barium esophagram to define the distance from the esophagogastric junction to the top of a distinct barium column and measure maximal esophageal width. Patients diagnosed with achalasia were subsequently offered the therapeutic options of either pneumatic dilation or laparoscopic Heller myotomy, and the decision on the type of treatment was arrived through a patient–physician discussion of risks and benefits. No patients refused therapy. Pneumatic dilation occurred according to current guidelines (Am J Gastroenterol 1999;94:3406–3412) using a graded rigiflex balloon starting with a 30-mm balloon with repeat dilation with 35-mm balloon for failures at 4 weeks, and 40-mm balloon if needed subsequently. Heller myotomy was laparoscopic in 88% of patients and open in 12% of patients who underwent surgery before 1998. Antireflux procedures were performed in 33% of the patients undergoing myotomy. Follow-up was obtained in 2003 using a structured telephone interview, and patients were invited to return to the Cleveland Clinic for a timed barium esophagram.

The success of a single pneumatic dilation was defined as freedom from subsequent dilations. The success of graded pneumatic dilation and Heller myotomy was freedom from cross-over to alternative therapies. Additional endpoints were perforations from pneumatic dilation, and heartburn requiring PPI therapy. A nonproportional hazard model was used to analyze time to failure.

Over the study period, a total of 169 patients were identified; 10 were excluded due to insufficient chart data, 106 patients underwent initial pneumatic dilation, and 53 Heller myotomy. Twenty patients failing pneumatic dilation crossed over to surgery. Patients undergoing pneumatic dilation were significantly older (mean 52 years versus 47 years, P = .02), and the average follow-up period was 3.1 years (range, 0.1–8.4 years).

Freedom from a second pneumatic dilation was 62% at 6 months, and 50%, 38%, and 28% at 2, 4, and 6 years, respectively. Four variables were associated with an increased early risk for need for second pneumatic dilation: younger age, male gender, wider esophagus at 1 minute on baseline timed barium esophagram, and no improvement in barium height at 5 minutes 1 month after treatment. For both genders, but particularly for men, there was an age-related response, with improving success as age increased. Women had a better outcome with a single dilation. The perforation rate overall was 2 in 106 (1.9%).

Forty-nine (46%) of the 106 patients required a second dilation and 6 patients required a third dilation. The success rates using graded pneumatic dilation in this cohort was 90% at 6 months, and 82%, 64%, and 44% at 2, 4, and 6 years, respectively. No risk factors for early or late treatment failure were identified in the cohort with a second or third dilation.

Of the 73 patients who were treated initially or subsequently with Heller myotomy, freedom from treatment cross-over was 89% at 6 months, and 86%, 78%, and 57% at 2, 4, and 6 years, respectively. No risk factors for early failure were identified. There was no significant difference in outcomes after pneumatic dilation or Heller myotomy; the success rates of both treatments demonstrated progressive decline over time. Patients failing after Heller myotomy showed a plateau in hazard for approximately 3 years before symptomatic relapse, whereas the relapse rate after pneumatic dilation appeared constant over time. There was a statistically significant increase in heartburn symptoms in patients who had undergone prior Heller myotomy (56% versus 26%, P < .01). Prior injection of botulinum toxin did not affect outcome of either procedure. Pneumatic dilation failure was caused by incompletely treated achalasia in 22 of 23 (96%) patients and gastroesophageal reflux in 1 patient (4%); failure in the Heller myotomy cohort was attributed to achalasia in 9 of 14 (64%) and GERD in 5 (36%) patients. New-onset gastroesophageal reflux requiring PPI therapy developed in 56% of the myotomy cohort, with severe dysphagia/regurgitation requiring frequent dilation in 36% of patients failing treatment.

Comment. Achalasia is a primary esophageal motility disorder of unknown etiology characterized by insufficient relaxation of the LES, loss of esophageal peristalsis, and poor esophageal emptying of barium. Unfortunately, most cases of achalasia are misdiagnosed for several years, most commonly as GERD (Gut 1992;33:1011–1015). In one series of 87 patients with achalasia, the mean symptom duration was 4.7 years (Dig Dis Sci 1997;42:580–585). The diagnosis of achalasia is based on the classic appearance of a dilated esophagus on upper barium study with a tapered “bird-beak” appearance owing to the high pressure of the LES. In early cases of achalasia, however, the barium study can appear relatively normal. Therefore, an esophageal motility study is necessary to confirm the diagnosis, and should be performed in patients with progressive dysphagia or GERD symptoms not responding to PPI therapy. Required features on esophageal motility studies for the diagnosis of achalasia include incomplete relaxation of the LES, and aperistalsis in the distal two thirds of the esophagus. Other supportive features include elevated pressure of the LES and elevated intraesophageal pressure.

Available therapies for achalasia include medical therapy, directed injection of botulinum toxin into the LES, graded pneumatic balloon dilation, and laparoscopic or open Heller myotomy. Medical therapy with nitrates or calcium channel blockers may transiently improve symptoms of dysphagia by relaxing the LES, but these agents are not effective in providing long-standing symptom relief (Gastroenterology 1982;83:963–969). Endoscopic injection of botulinum toxin into the LES has been shown to offer initial symptomatic relief in approximately 60%–80% of patients (Gut 1997;41:87–92) and positive symptom response can be useful as an additional confirmation of the diagnosis. However, the majority of patients will experience symptomatic relapse within 1–2 years, (Gastroenterology 1996;110:1410-1415; Aliment Pharmacol Ther 2006;23:1615–1619) and the duration of the effect declines with repeated injections over time. Therefore, this therapy should be reserved for patients who are not candidates for endoscopic or surgical therapy.

The 2 major therapeutic options for patients remain pneumatic balloon dilation of the LES and Heller myotomy. Unfortunately, there is no standardized definition of therapeutic success for patients with achalasia, and success rates in the literature depend on the definitions used for relapse based on symptomatic frequency and severity. Patients opting for pneumatic dilation should be advised that gender and age are important prognostic factors. Based on the available literature, the success rate for pneumatic dilation appears higher for women, and increases with advancing age for both genders. A prior study from the Cleveland Clinic in 2004 demonstrated that pneumatic dilation with a 3-cm balloon was more likely to fail in younger men compared with older men (P = .04; Clin Gastroenterol Hepatol 2004;2:389–394). Therefore, using the graded dilators, good to excellent response occurs in 50%–93% of patients postdilation, with improving response with increasing size of the balloon dilators. Success rates in patients undergoing pneumatic dilation after failed Heller myotomy are not as favorable as untreated cases undergoing dilation (J Clin Gastroenterol 2004;38:855–860). A cost-effectiveness model with a 5-year time horizon comparing pneumatic dilation to Heller myotomy and botulinum toxin injection concluded that pneumatic dilation was preferred with an incremental cost-effectiveness ratio of $1348 per quality-adjusted life-year gained.

Surgical myotomy using a laparoscopic Heller myotomy demonstrates good to excellent symptom relief in 70%–90% of patients, with low mortality rates (approximately 0.2%). Reflux complications remain the most common, but the role of fundoplication remains controversial. A study of 149 patients undergoing Heller myotomy, 88 (59%) of whom underwent Dor fundoplication demonstrated decreased percentage time that the esophageal pH < 4.0 after fundoplication without impairing esophageal emptying in patients undergoing laparoscopic Heller myotomy (J Thorac Cardiovasc Surg 2005;130:1593–1600). Conversely, a small study of 33 patients who underwent laparoscopic Heller myotomy without fundoplication (using a 7-cm myotomy that included the LES but did not exceed 5 mm of the gastric cardia) with at least 24 months of follow-up did not demonstrate gastroesophageal reflux by ambulatory pH monitoring in any patients, and concluded that the risk of gastroesophageal reflux is very low when the cardiomyotomy does not exceed the length of 5 mm (J Laparoendosc Adv Surg Tech A 2006;16:345–349). A recent meta-analysis of 15 studies where an antireflux procedure accompanied laparoscopic myotomy in 532 patients demonstrated no significant difference in postmyotomy pH studies in patients with or without fundoplication (Surg Endosc 2003;17:554–558).

Current guidelines suggest either initial laparoscopic myotomy or graded pneumatic dilation for patients who are at low surgical risk with achalasia (Am J Gastroenterol 1999;94:3406–3412). Many physicians recommend initial myotomy based on a belief that surgery may be associated with more favorable long-term outcomes. However, by comparing both pneumatic dilation and Heller myotomy, the results from the current study reinforce the fact that no treatment cures achalasia. Although Heller myotomy may be associated with fewer symptoms within the first 3 years, the long-term outcomes after both procedures appear to be equivalent and demonstrate decline over time. However, based on this study, revision to the current guidelines could be considered. Because the current data support lack of efficacy of pneumatic dilation in younger men, perhaps this cohort should be offered Heller myotomy, or initial dilation with a 3.5-cm balloon rather than a 3-cm balloon as currently recommended. In contrast, women may be treated initially with pneumatic dilation using a 3.0-cm balloon and expect good initial results from a single dilation. Older patients could consider the option of graded pneumatic dilation because the success rate of dilation improved with advancing age. Both genders should receive appropriate counseling regarding the potential development of GERD after Heller myotomy. More studies are needed assessing potential development of GERD-associated complications including Barrett’s esophagus and esophageal adenocarcinoma. Ultimately the decision for initial therapy is based on the patient’s decision, but the current study by Vela et al allows gastroenterologists to educate patients more accurately about expected long-term outcomes. Based on the current data, all patients with achalasia require long-term follow-up evaluation after initial therapy.