Background and Aims: A rat model of severe esophagitis is induced by performing either an esophagoduodenostomy (ED, acid and non-acid/bile reflux) or esophagoduodenostomy with total gastrectomy (ED + TG, non-acid reflux only). Esophagitis is not found in control animals in which total gastrectomy with Roux-en-Y reconstruction is performed (TG+RY, no reflux). All three operations result in formation of well-differentiated tumors at the esophageal anastomosis. Consequently, the nature of these tumors is controversial. COX-2 is overexpressed in a stepwise manner in esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. The aim of this study was to (1) compare esophageal cyclo-oxygenase 2 (COX-2) expression in the three operation models, and (2) characterize the tumors.
Methods: COX-2 enzyme expression was measured in the distal esophageal mucosa of 60 rats, 20 in each operation group, using a polyclonal rabbit antibody. Tumor and normal tissues were examined for DNA content and apoptotic index using flow cytometry with immunofluorescent propidium iodide and annexin V labeling, and for protein expression using immunohistochemistry.
Results: COX-2 expression was higher than controls in severe esophagitis in both ED and ED+TG arms but was significantly higher in the non-acid bile reflux ED+TG arm. The tumors were diploid in 5 of the 6 examined and the remaining animal had aneuploidy in both tumor and normal tissues. None of 12 tumors examined showed immunoreactivity with p53, DAS-1, c-erbB-2, CEA, chromogranin A, or synaptophysin antibodies.
Conclusions: Injury severity, as measured by COX-2 overexpression, was significantly higher in a non-acid reflux environment in this animal model of esophagitis. The esophageal tumors that developed in this surgical model without exogenous carcinogen exposure were dissimilar to human esophageal adenocarcinomas.