P1.023. Mechanism of Esophageal Carcinogenesis Due to Bile Acid Reflux

Topic Esophageal Cancer: Esophageal Carcinogenesis Background . Miwa demonstrated that reflux of gastric juice alone is insufficient to induce esophageal carcinoma,. To investigate the effects of duodenal reflux on the esophagus, we created a model which the esophagus and duodenum were anastomosed end-to-end after total gastrectomy and examined the effects of duodenal juice on the esophageal mucosa. Methods Forty male Wistar rats, 8 weeks were used. In the esophagoduodenal anastomosis model, the esophagus and duodenum were anastomosed end-to-end (EDA) after total gastrectomy (n = 30), and in the control group (n = 10), the laparotomy was repeated under anesthesia 35 weeks after surgery, and the entire esophagus was rapidly removed along with the duodenum at the anastomosis site. After measuring intraesophageal bile acid concentrations, the esophagus was incised at the anterior wall and subjected to HE staining, PCNA and COX2 immunostaining, and a portion was frozen for PGE2 measurement. Five EDA and control cases underwent laparotomy under anesthesia at 35 weeks, and a 27F tube was inserted into the common bile duct for bile analysis. Results I. Macroscopic findings of the esophagus: In the EDA group, The middle and lower esophagus exhibited erosion, an irregular surface, and small elevated tumors. 2. Esophageal histological findings: EDA group, dysplasia, were observed in all cases, with SCC and ADC occurring in 33% and 30%, respectively. 3. COX2 : COX2 uptake was also observed in SCC and ADC to approximately the same extent. 4. Tissue PGE2: The EDA group showed significantly higher values than the sham group 5. PCNA labeling index (LI): The EDA group showed a significantly higher value than the sham group ). 6. Bile acid in esophageal reflux fluid: The EDA group showed a significantly higher value than the sham group . 7.Bile acids in the common bile duct (mmol/L):The EDA group showed significantly higher than the sham in total bile acids,taurocholic acid,tauroursodeoxycholic acid, taurochenodeoxycholic acid taurochenodeoxycholic acid Conclusion It is speculated that chronic stimulation by duodenal reflux, particularly bile acids (taurocholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid, taurochenodeoxycholic acid), led to the expression of COX2 in the esophageal epithelium, the expression of PGE2, and the activation of cell proliferation, resulting in the development of severe dysplasia and cancer (SCC, ADC). It is thought that bile reflux into the esophagus is strongly involved in the development of not only adenocarcinoma but also squamous cell carcinoma.