duodenogastric reflux without carcinogens: morphology, mucin histochemistry, polyamine metabolism, and labelling index

Chronic duodenogastric reflux induces gastric adenocarcinomas in the rat without the use of carcinogens. Altogether, 186 male Wistar rats were randomised to undergo either a simple gastrojejunostomy or a gastrotomy and sacrificed at eight weekly intervals for 56 weeks. No control animals developed dysplasia or carcinoma. All rats subjected to a gastrojejunostomy showed hyperplasia of the proliferative neck zone, with increased sulphomucin production adjacent to the scar. Low grade dysplasia was found at 16 weeks, and carcinoma was first seen at 32 weeks. Most carcinomas were well differentiated mucin secreting adenocarcinomas of the expanding type, which secreted a mixture of sialomucins and sulphomucins. Duodenogastric reflux was associated with a 100% increase in labelling index (assessed autoradiographically with tritiated thymidine) in the gastric mucosa when compared with corresponding tissue adjacent to a gastrotomy scar. This increase was significant at eight weeks and persisted for 56 weeks after surgery. This study supports the theory that, in this model, hyperplasia precedes the development of carcinoma. Departments of Surgery P R Taylor R C Mason D C Hanley I McColl Gastroenterology S Vaja GM Murphy R H Dowling and Histopathology, UMDS, Guy's Hospital, St Thomas Street, London SEI 9RT M I Filipe Correspondence to: Mr R C Mason. Accepted for publication 28 January 1991 The incidence of gastric stump cancer remains controversial." A large recent series, however, has shown that gastric surgery for benign disease is associated with a pronounced increase in gastric adenocarcinoma when compared with a control population from the same locality.7 Studies in experimental animals have shown that gastric surgery can induce adenocarcinoma of the stomach without the use of carcinogens.8 Furthermore, the incidence of malignant change in the gastric mucosa was proportional to the degree of duodenogastric reflux. In this rat model of duodenogastric reflux the pancreaticoduodenal secretions, rather than the bile, seemed to be responsible for the tumour.9 In tissues which have a high proliferative rate the activity of the rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase, and the concentrations of the polyamines are relatively high. Many human cancers also show high levels of ornithine decarboxylase activity in the malignancy. Since duodenogastric reflux is a reliable model for inducing gastric cancer, and since polyamine metabolism has never been studied in the gastric mucosa in this model, we examined the sequential longterm effects of duodenogastric reflux on gastric mucosal morphology, mucin histochemistry, ornithine decarboxylase activity, and polyamine concentration and correlated the results with the labelling index assessed autoradiographically, an established method of measuring tissue proliferation.