Histopathology of mouse esophagus after reflux surgery. (A) In the non-operated control group, the basal layer of the epithelium was smooth and the nuclei were in a single line. (B) The epithelium responded to surgery-induced reflux with hyperplasia. Layers of the squamous epithelium increased and papillae were enlarged. (C) After long-term reflux, the epithelial cells started to lose their polarity with condensed nuclei and increased mitosis. (D) Later on, the squamous epithelium lost its normal architecture. Dysplastic cells penetrated the basal membrane and invade into the stroma. (E) At 20 weeks after the surgery, mucin-producing cells were observed in the parabasal layer of the squamous epithelium. (F) Alcian blue staining confirmed mucin secretion in these scattered mucinous cells. (G, H) At 80 weeks after surgery, squamous cell carcinoma was observed in the Swiss-rolled esophagus of a mouse in Group B. Panel H is magnification of part of Panel G.