Reflux of duodenal or gastro-duodenal contents induces esophageal carcinoma in rats

Abstract

Chronic reflux esophagitis precedes Barrett's esophagus, which is defined as the columnar-lined epithelium replacing the original squamous epithelial cell lining of the esophagus. Barrett's esophagus carries a risk of malignant transformation to adenocarcinoma. Patients with complicated Barrett's esophagus reflux significantly greater amounts of both acid and duodenal contents than patients with uncomplicated Barrett's esophagus (Vaezi and Richter, 1995). Individuals with a history of gastrectomy often suffer from alkaline reflux esophagitis, and their esophageal carcinoma often develops in the lower third of the esophagus, whereas esophageal carcinoma in patients not subjected to gastrectomy is most frequently located at the middle third of the esophagus (Maeta et al., 1990). Gastric-stump carcinogenesis is associated with duodenogastric reflux. Development of experimental esophageal carcinoma induced by carcinogens is promoted by reflux of duodenal contents (Pera et ab, 1989; Seto et al., 1991; Attwood et al., 1992; Clark et al., 1994) and duodenal contents per se induce rat gastric carcinoma (Miwa ei ai., 199%). This clinical and experimental evidence favors the view that esophageal mucosa may be susceptible to duodenal contents in esophageal carcinogenesis. We have reported that duodenogastric reflux is associated with forestomach and esophageal carcinogenesis in rats (Miwa et al., 1994). However, it is still unresolved which secretions of the refluxate, duodenal or gastric contents, are responsible. In this study we investigate whether reflux of duodenal andtor gastricjuice can cause esophageal carcinogenesis in rats. MATERIAL AND METHODS Experimental animalsWistar male rats weighing approximately 250g were used. They were housed 3 to a cage, and maintained under conditions of 22 2 3°C room temperature and 55 _C 5% humidity with a 12-hr light-dark cycle. They were fed a standard solid chow CRF-1 (Charles River, Japan) and tap water. Surgical proceduresAfter 24 hr fasting, the rats received an upper abdominal incision under diethyl-ether inhalation anesthesia. Then one of the surgical procedures illustrated in Figure 1 was performed on each rat.Gastro-duodeno-esophageal reflux (GDER) (n = 30). After the bilateral vagus nerves were preserved, the abdominal esophagus was transected under the diaphragm, and the distal cut end was closed with sutures. The esophageal stump was anastomosed end-to-side to a loop of jejunum 4 cm distal to Treitz's ligament in an ante-colic manner. This procedure allowed gastro-duodenal contents to flow back into the esophagus.Duodeiio-esophageal reflux (DER) (n = 30). The glandular stomach and forestomach were removed (total gastrectomy), before the duodenal stump was closed with sutures. The esophageal stump was then anastomosed end-to-side to the jejunum approximately 4 cm distal to Treitz's ligament. This surgery induced reflux of duodenal contents into the esophagus.Gastro-esophageal reflu (GER) (n = 30). After the bilateral vagus nerves were preserved, the abdominal esophagus w...

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.…”

“…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. 6,30,31 Miwa et al suggested that the incidence of CLE might be dependent on the amounts of duodenal contents into the esophagus. By using gastroduodenoesophageal reflux models, ADC within CLE always occurred in the lower esophagus near the anastomotic line, where more is regurgitated, and SCC surrounded by chronic squamous esophagitis was observed distant from the site of anastomosis.…”

“…By using gastroduodenoesophageal reflux models, ADC within CLE always occurred in the lower esophagus near the anastomotic line, where more is regurgitated, and SCC surrounded by chronic squamous esophagitis was observed distant from the site of anastomosis. 6 Barrett esophagus appeared to arise in the regenerative process in response to severely chronic inflammation through excessive reflux. In this study, the large capacity of the forestomach and the buffer effect of gastric juice in the presence of the glandular stomach may have decreased the degree of reflux injury to the squamous epithelium.…”

“…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.…”

Description of the technique of upper gastrointestinal series radiological examination for the evaluation of the esophagus, stomach and duodenum of Wistar female rats

“…In the esophageal perforation, the diagnosis by contrast examination reveals the occurrence of contrast runoffs in 90% of the cases investigated 9,10 . The contrast radiology of the upper gastrointestinal series did not show contrast runoff occurrences, in any of the specimens investigated, or any type of lesion that was visible even after the conduction of subsequent necropsy 14 .…”