Induction of oesophageal and forestomach carcinomas in rats by reflux of duodenal contents

Abstract

S_mmmmary A study was designed to determine whether oesophageal carcinomas can be induced through reflux of duodenal contents. Male Wistar rats weighing 230 -250 g were divided into three groups according to the surgical procedure performed: (1) the duodenal contents were directed into the forestomach through a stoma (duodeno-forestomach reflux); (2) the duodenal contents were regurgitated into the forestomach through the glandular stomach (duodeno-glandular-forestomach reflux); and (3) a sham operation was performed as a control. Animals were fed standard CRF-1 solid food and tap water that was not exposed to carcinogens and were sacrificed 50 weeks post-operatively. While no neoplasia was observed in any of the 32 control rats, 4/11 (36%) with duodeno-forestomach reflu.x and 3/18 (17%) animals with duodeno-glandular-forestomach reflux developed carcinomas in the lower oesophagus and forestomach. The incidence in each group was significantly higher than in the controls (P<0.01 and P<0.05 respectively). Six of the seven lesions consisted of squamous cell carcinomas, and one was a mucinous adenocarcinoma. Oesophageal columnar epithelial metaplasia was observed in two (18%) of the animals with duodeno-forestomach reflux. Carcinomas were always surrounded by chronic inflammatory changes, including regenerative thickening, basal cell hyperplasia and dysplasia. Additional well-differentiated adenocarcinomas were observed in the prepyloric antrum of 6/18 (33%) animals with duodeno-glandular-forestomach reflux. These findings indicate that chronic reflux of duodenal contents may cause oesophageal carcinoma.Oesophageal adenocarcinoma frequently occurs in the lower oesophagus, in the bed of the columnar-lined epithelium (Barrett's oesophagus) (Naef et al., 1975;McDonald et al., 1977; Witt et al., 1983;Miros et al., 1991). This columnarlined epithelium develops in response to gastro-oesophageal reflux (Mossberg, 1966;Halvorsen & Semp, 1975;Gillen et al., 1988; Seabrook et al., 1992). Thus, the association of adenocarcinoma with gastro-oesophageal reflux is well established. However, there are few data indicating whether squamous cell carcinoma, by far the most frequent type of oesophageal carcinoma, may also occur as a result of reflux. Some clinical evidence supports this assumption. Individuals with a history of gastrectomy occasionally develop squamous cell carcinomas in the lower oesophagus, probably as a consequence of post-surgical reflux oesophagitis (Shearman et al., 1970;Rossi et al., 1984;Maeta et al., 1990;Seto et al., 1991). Long-lasting reflux oesophagitis following oesophageal hiatus hernia is known to be closely related to the occurrence of oesophageal cancer (Kuylenstierna & Munck-Wikland, 1985). Epidemiological studies reveal that a form of chronic oesophagitis, which is thought to result from nutritional deficiencies, is the most frequent lesion found in populations at high risk of oesophageal cancer in such areas as Kashmir in India, southern Africa, northern Iran and Linxian and Huixian in China (Cres...

Gastric proliferative lesions induced by duodenogastric reflux in rats

“…In the squamous epithelium that lines the proximal third of the stomach the presence of squamous hyperplasia was found, with a frequency that did not significantly differ between the animals in groups II and III. These results differ from those obtained by Miwa et al 11 that reported development of squamous cell carcinoma in a model of induction of duodenogastric reflux similar to the present study, although the follow-up period was 50 weeks and the anastomosis was located close to the greater curvature of the squamous stomach.…”

“…At present, authors endeavor to better evaluate the potential relationship between the primary duodenogastric reflux that takes place through the pylorus in fasting and postprandial conditions, in non-operated stomachs, and neoplastic development 10,11,12,13 . Most of stomach neoplasias appear in an environment of chronic atrophic gastritis with intestinal metaplasia 11 .…”

“…Most of stomach neoplasias appear in an environment of chronic atrophic gastritis with intestinal metaplasia 11 . The intensity of glandular atrophy and intestinal metaplasia is directly related to the reflux of duodenal secretions in the gastric mucosa 14 .…”

A selective cyclooxygenase‐2 inhibitor prevents inflammation‐related squamous cell carcinogenesis of the forestomach via duodenogastric reflux in rats

“…5,6 Repeated mucosal damage because of DGR finally induces SCC, which follows a process of initial BCH and subsequent DYS. In this study, duodenal regurgitation into the forestomach was not involved in the genesis of the columnar-lined epithelium (CLE) or ADC, in contrast to the pathogenesis in several duodenoesophageal reflux models.…”

“…We previously demonstrated in rats that reflux of duodenal contents causes carcinogenesis in the forestomach and the esophagus without any carcinogens. 5,6 The histological spectrum of these carcinomas includes ADC, SCC, and adenosquamous carcinoma. Our experimental results showed a close association between an inflamed squamous epithelium and the genesis of SCC in duodenal reflux models.…”