Surgical myotomy and pneumatic dilatation, the standard treatment for esophageal achalasia, carry a significant risk for major complications, notably gastroesophageal reflux and perforation [1, 2]. Intrasphincteric injection of botulinum toxin has been reported as a safe and effective novel short-term treatment [3]. The results were similar to those seen with dilatation [4]; moreover, the toxin was also effective in patients in whom myotomy or dilatation was unsuccessful [5].

We prospectively investigated the long-term safety and efficacy of endoscopic injection of 100 U of Botox (Allergan, Inc., Irvine, California) into the lower esophageal sphincter in 54 consecutive patients. Response was assessed on the basis of symptoms (frequency of dysphagia, regurgitation, and chest pain, scored on a scale ranging from 0 to 3), esophageal manometry, and esophageal radionuclide emptying.

One month after treatment, 47 patients (87%) were responders (symptom score 2). The alleviation of symptoms was paralleled by reductions in lower esophageal sphincter pressure (mean ±SD, 21 ± 9 mm Hg compared with 33 ± 11 mm Hg in nonresponders; P < 0.002) and esophageal retention (27% ± 17% compared with 50% ± 22%; P < 0.001) (Figure 1). After a mean follow-up of 16 ± 9 months (range, 5 to 39 months), 40 patients (74%) were still in remission, although 16 and 9 patients had been injected two and three times, respectively, when symptoms recurred. The Kaplan-Meier probability of remission at 3 years was 70%. The efficacy of the first and second injection lasted for 7.3 ± 5 and 10.2 ± 6.3 months, respectively. Neither serious adverse events nor symptoms of gastroesophageal reflux were reported. Responders were older (53 ± 19 years compared with 40 ± 18 years; P < 0.04) and less symptomatic (symptom score, 5.4 ± 1.3 compared with 6.5 ± 1.1; P < 0.008) than nonresponders. Pretreatment esophageal function tests, however, did not predict outcome.

View larger version (19K): [in this window] [in a new window]   Figure 1. Modifications in symptom score, basal left esophageal sphincter (LES) pressure, and percentage of esophageal retention 1 month after the first injection of botulinum toxin.

Intrasphincteric injection of botulinum toxin is effective and safe for the long-term treatment of achalasia. Two thirds of patients have a sustained response if therapy is repeated when symptoms relapse. Failures occurred more frequently within the first months, in younger patients, and in patients with a long duration of dysphagia and higher symptom scores.