Etiology of gastric remnant cancer with special reference to the effects of denervation of the gastric mucosa

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Abstract
Gastric mucosal blood flow, secretion of mucin, and renewal of the gastric mucosal cells are considered to be defensive factors against gastric mucosal injuries. These factors are regulated by the nervous system and neuropeptides. Gastrectomy may affect this regulation and induce gastric mucosal changes, such as atrophic gastritis and carcinoma. The effects of denervation of the gastric mucosa on tumorigenesis of the remnant stomach were investigated. Using male Wistar rats, four groups of Billroth I (B-I)gastrectomy, Billroth II (B-II) gastrectomy, and those with denervation were conducted. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after the operations, histologic examination and periodic acid-Schiff--Alcian blue (PAS-AB) staining of the gastric mucosa, analysis of cell kinetics of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen, and measurement of intragastric pH, intragastric bile acid concentration, and serum gastrin levels were performed. No carcinogenic agents were given. The B-I group showed no remarkable gastric mucosal changes, but B-I with denervation showed a significant increase in the development of tumor (67%) and carcinoma (42%). In the B-II groups, the denervation induced a significant increase in tumorigenesis, from 22% to 58%. Analysis of cell kinetics revealed a significant increase of labeling index in those groups that developed tumors. PAS-AB staining showed a decrease of PAS positive mucin but an increase of acidic mucin-producing cells in the denervated groups, suggesting an increase in the number of immature cells that are more susceptible to atrophic gastritis and carcinoma. There was no close relationship between tumorigenesis and intragastric pH, intragastric bile acid concentration, or serum gastrin levels. After gastrectomy, not only duodenogastric reflux, but also the denervation of the gastric mucosa play an important role in the etiology of gastric remnant cancer.