Botulinum toxin was less efficacious than pneumatic dilatation for achalasia
ACP J Club. 1999 July-Aug;131:17. doi:10.7326/ACPJC-1999-131-1-017
Vaezi MF, Richter JE, Wilcox CM, et al. Botulinum toxin versus pneumatic dilatation in the treatment of achalasia: a randomized trial. Gut. 1999 Feb;44:231-9.
Is botulinum toxin more efficacious than pneumatic dilatation for achalasia?
Randomized controlled trial with 12-month follow-up.
Cleveland Clinic Foundation and University of Alabama at Birmingham, USA.
Patients (age range 37 to 70 y, 65% men) who received a first diagnosis of achalasia from 1995 to 1997 on the basis of manometry (incomplete lower esophageal sphincter [LES] relaxation and esophageal body aperistalsis) and barium esophagram (esophageal dilatation, aperistalsis of esophageal body, and narrowed LES). Exclusion criteria were previous pneumatic dilatation or surgical myotomy; age < 18 years; or achalasia associated with gastric or esophageal cancer, neuromuscular disorder, pregnancy, cardiovascular disability, or coagulopathy.
24 patients were allocated to injected botulinum toxin, 100 units into the LES; those with < 50% symptom improvement after 1 month received a second injection. 24 patients were allocated to pneumatic dilatation with a Rigiflex dilator using a 3.0-cm balloon; those with < 50% improvement after 1 month had repeated pneumatic dilatation with a 3.5-cm balloon.
Main outcome measures
Clinical response defined as clinical remission (> 50% improvement in total symptom severity score [sum of scores for dysphagia, regurgitation, and chest pain]), early failure (< 50% improvement after 2 treatments and required alternative treatment), or late failure (> 50% improvement initially, with later relapse). Objective measures of esophageal function (blindly assessed) included LES pressure and esophageal emptying (barium height and width).
42 patients (88%) were included in the efficacy analysis. At 12 months, the pneumatic dilatation group had a higher cumulative remission rate than the botulinum group (70% vs 32%, P < 0.02). Intention-to-treat analysis showed similar results (58% vs 29%, P = 0.02). The groups did not differ for early failures, but more late failures occurred in the botulinum group (7 vs 1 patient, P = 0.02). Over 12 months, patients who had pneumatic dilatation had a greater percentage decrease in esophageal barium height (P = 0.04) and a greater over-all mean percentage decrease in esopha-geal width (53.2% vs 25.6%, P < 0.01).
Among patients with achalasia, pneumatic dilatation led to greater improvements in symptoms and esophageal function than botulinum toxin at 1 year.
Source of funding: American College of Gastroenterology Institute for Clinical Research and Education.
For correspondence: Dr. J.E. Richter, Department of Gastroenterology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. FAX 216-444-9047.
This may be the best study of achalasia ever done. These experienced esophagologists have impeccable credentials in diagnosis, endoscopic expertise, and an appreciation of science. They had many cases of this relatively uncommon esophageal malady, and few institutions could match patient accession.
Still, it is always difficult to read manuscripts describing endoscopic clinical trials. As in surgical studies, pneumatic dilatation by Joel Richter is not likely to be the same procedure as the identical "code" from the average community gastroenterologist. Further, controversy exists about the most satisfactory way to apply the pneumatic dilator in terms of dilator size and duration of inflation (1).
Even botulinum injection may differ between gastroenterologists. Nevertheless, these results can guide us in the application of available therapeutic technology for patients with achalasia. They suggest an unequivocal advantage for pneumatic dilatation over botulinum toxin, particularly for long-term remission. If these results are accepted without question, practitioners should choose pneumatic dilatation for almost all of their patients (except for those with severe comorbid conditions or advanced age). The data, however, can be interpreted otherwise. Patients who had pneumatic dilatation had 2 perforations despite the expertise of these clinicians, and 1 patient had esophagectomy. The lower success rate of botulinum toxin may be counterbalanced by important complications of pneumatic dilatation, a procedure considered by squeamish gastroenterologists to be particularly aggressive.
Patients with achalasia should now be offered pneumatic dilatation because it is most likely to provide satisfactory long-term results. I suspect, however, that some gastroenterologists and their patients will continue to be seduced by the relative ease and short-term safety of botulinum injections. Although it seems unlikely that a better comparative trial will be done, our research-minded colleagues might try to improve results of the less-invasive procedure to make it more similar to pneumatic dilatation.
Malcolm Robinson, MD
University of OklahomaOklahoma City, Oklahoma, USA