An esophagogastroduodenal anastomosis model for esophageal adenocarcinogenesis in rats and enhancement by iron overload

The aim of this study is to establish a good animal model for esophageal ad enocarcinoma (EAC) and to test the hypothesis that iron over-nutrition enha nces EAC formation. With rats, esophagogastroduodenal anastomosis (EGDA) wa s accomplished by anastomosing the duodenum to the gastroesophageal junctio n. Iron supplementation was given by i.p. injection of iron dextran (4 mg F e/kg/week), This model mimics the development of human EAC by introducing m ixed reflux of gastric and duodenal contents. At 40 weeks after surgery, th e body weight, food intake, hemoglobin, total serum iron, transferrin satur ation, serum albumin, and plasma levels of alpha-tocopherol, gamma-tocopher ol and retinol of the EGDA rats were not significantly different from those of the non-operated controls. The animals generally had only mild esophagi tis, except that the area surrounding the anastomosis opening had more seve re esophagitis, Columnar-lined esophagus (CLE), CLE with dysplasia, and EAC were diagnosed in 53.5, 34.9 and 25.6%, respectively, of the 43 rats. Intr aperitoneal iron supplementation significantly enhanced esophageal lesions with CLE, CLE with dysplasia, and EAC to 78.0, 53.7 and 53.7%, respectively , of the 41 rats. All the tumors were well-differentiated mucinous adenocar cinomas at the squamocolumnar junction area, where most iron deposition was observed. EGDA avoids nutritional problems seen in other animal models for EAC, We believe that direct anastomosis of squamous epithelium to columnar epithelium and mixed reflux of gastric and duodenal contents lead to the f ormation of CLE and EAC, With this model, we demonstrated that iron supplem entation significantly enhanced EAC formation, suggesting that iron over-nu trition could also be a risk factor for human EAC.