Esophageal and gastric nitric oxide synthesizing innervation in primary achalasia

OBJECTIVE: We performed a qualitative and quantitative analysis of the nitr inergic neurons in the esophageal and gastric component of the lower esopha geal sphincter (LES) and gastric fundus of patients with primary achalasia. METHODS: Four muscle strips were obtained from the esophagogastric junction (two from the esophageal and two from the gastric side of the LES), and tw o from the gastric fundus of six patients with endstage achalasia who under went an esophagogastric myotomy plus hemifundoplication. Control specimens were obtained from eight patients who underwent surgery for cancer of the t horacic esophagus. Fixed sections were processed for NADPH-diaphorase histo chemistry and the number (mean +/- SE) of nitrinergic neurons per section w as visually quantified in each specimen. RESULTS: In the controls, nitric oxide fibers were distributed to the muscl e layer and surrounding myenteric neurons of both the LES and the gastric f undus. By contrast, achalasic patients showed a marked decrease of nitric o xide nerves and labeled neurons in both esophageal and gastric components o f the LES and the gastric fundus. Quantitative assessment in achalasic pati ents showed that the mean number of nitrinergic neurons was dramatically re duced in both the esophageal (0.2 +/- 0.1) and the gastric component (2 +/- 0.6) of the LES as compared to those in controls (15 +/- 5 and 12 +/- 4, r espectively; p < 0.05); nitrinergic neurons in the gastric fundus (3 +/- 1) were significantly reduced in comparison to those of controls (10 +/- 2) ( p < 0.05). CONCLUSIONS: Our results indicate that achalasia is a motor disorder with a n intrinsic inhibitory denervation of the esophageal and gastric component of the LES and of the proximal stomach, thus providing further evidence for an extraesophageal extension of the disease. (Am J Gastroenterol 1999;94:2 357-2362. (C) 1999 by Am. Coll. of Gastroenterology).