Duodenal-content reflux esophagitis induces the development of glandular metaplasia and adenosquamous carcinoma in rats

Recent studies have demonstrated that refluxed duodenal contents cause esop hageal carcinoma in rats without exposure to carcinogens, The histopatholog ical spectrum of these carcinomas includes squamous-cell carcinoma, adenoca rcinoma and adenosquamous carcinoma. Pure adenocarcinomas are thought to ar ise in areas of columnar metaplasia adjacent to the anastomosis, similar to Barrett's esophagus in humans. In contrast, the histogenesis of adenosquam ous carcinomas is unclear. The purpose here was to investigate the pathogen esis of esophageal adenosquamous carcinomas in a time-course experiment of chronic duodenal-content reflux without carcinogen. Forty-two 8-week-old ma le Sprague-Dawley rats were divided into seven groups and exposed to duoden al-content esophageal reflux during 10, 15, 20, 25, 30, 35 and 40 weeks, re spectively. All animals underwent an esophagojejunostomy with gastric prese rvation in order to produce chronic esophagitis, The rats received a standa rd diet without addition of carcinogens, An increasing incidence of glandul ar metaplasia and carcinoma was observed over the time course, starting at 20 weeks. After 40 weeks of reflux, multiple foci of glandular metaplasia a nd adenosquamous carcinoma were found in 83 and 50% of the animals, respect ively. Most of the carcinomas occurred in the middle and proximal esophagus and had a dual pattern of differentiation, glandular and squamous, These f indings confirm that duodenal content reflux alone has a carcinogenic effec t. We propose that chronic duodenal reflux induces the development of metap lastic cells with glandular differentiation from the stem cells of squamous epithelium, and that glandular metaplastic foci are the morphological elem ent from which tumors with a dual pattern of differentiation arise.