Influence of surgically induced gastric and gastroduodenal content reflux on esophageal carcinogenesis - experimental model in Wistar female rats

Studies in human beings and animals have shown that esophageal exposure to duodenal and gastric contents may be important for the development of Barre tt's esophagus and its complications, including adenocarcinoma and epidermo id carcinoma. Diethylnitrosamine (DEN) is a carcinogen that stimulates the development of epidermoid carcinoma in the esophagus of mice. The aim of th is study,vas to evaluate the effect of gastroduodenal and gastric content r eflux; on induction of esophageal carcinogenesis, Gastroesophageal reflux ( CER) and gastroduodenoesophageal reflux (GDER) were produced by cardioplast y and esophagoduodenostomy. The chosen carcinogen was DEN, diluted in drink ing water, gic en 3 days a week for 20 consecutive weeks. One hundred Wista r female rats mere divided into sis groups, as follows: group 1 (18 rats), cardioplasty without DEN; group 2 (18 rats), cardioplasty with DEN; group 3 (10 rats), only water; group 1 (17 rats), cardioplasty with DEN; group 5 ( 17 rats), esophagoduodenostomy with DEN; group 6 (20 rats), only DEN. GER i n isolation induced group papillomatosis or ulceration in 22.2% of rats and , when associated with DEN, induced papillomatosis in 61.1% of rats. GDER i n isolation induced marked esophagitis in 61.1% of rats, Barrett's esophagu s in 16.7% and esophageal adenocarcinoma in 16.7%; when associated with DEN , 23.5% of rats presented marked esophagitis, papillomatosis or ulceration, whereas 76.5% had esophageal carcinoma, with 70.6% epidermoid carcinoma an d 5.9% adenocarcinoma. Rats treated with water alone did not show histologi c abnormalities of the esophageal mucosa, Rats treated with DEN alone devel oped papillomas in 50.0% of the cases and remained histologically unchanged in 50.0%, There was no development of low- or high-grade dysplasia in any group. The conclusions are that (1) GDER is significantly more deleterious to esophageal mucosa than GER; (2) in this study, GER did not present carci nogenic potential in relation to the esophagus; (3) GDER in isolation is an esophageal carcinogen, producing Barrett's esophagus and esophageal adenoc arcinoma; (4) esophageal oncogenesis caused by GDER is potentiated by DEN, inducing esophageal epidermoid carcinoma; (5) in this study, DEN in isolati on did not generate tumors in the esophagus of rats.