The Role of Esophagography in the Diagnosis of Orthotopic Esophageal Squamous Cell Carcinoma in a Mouse Mode.

PURPOSE/OBJECTIVE(S): Animal models play an irreplaceable role in pre-clinical studies of various tumors, mainly including xenogeneic/homograft subcutaneous tumor models. However, the subcutaneous transplanted tumor model is separated from the microenvironment of the primary tissue and fail to accurately simulate the growth of tumor cells in vivo. Therefore, orthotopic tumor models play an increasingly important role. For esophageal squamous cell carcinoma, chemotherapy-induced methods have successfully established mouse models of esophageal squamous cell carcinoma, but past experiments have found that it is still a challenge to confirm the success of the mouse model of esophageal cancer. The pathological diagnosis of the esophageal cancer tissue obtained from the killed mouse model remains the gold standard, but it also represents a lost opportunity to evaluate the efficacy of subsequent treatment. Notedly, esophagography is the primary examination for clinical patients with esophageal cancer. Therefore, the aim of this study is to evaluate whether esophagography can be used to establish a successful in situ mouse model of esophageal cancer.

MATERIALS/METHODS: Referring to previous literature, we used the chemical drug 4-Nitroquinoline N-oxide (4-NQO) to induce orthotopic tumor model: A certain amount of 4-NQO was dissolved in propylene glycol to make a 2% stock solution, and then dissolved in 200ml of sterile water for the daily drinking water of mice. The water was kept in the dark and replaced once a week. After 16 weeks of induction, the drinking water was replaced by the same volume of sterile water and continued to be fed for 12 weeks. The mice were subsequently subjected to esophagography: First, the mice were fixed on a plastic plate, and the gavage needle was slowly inserted into the stomach, then slowly withdrawn out and gradually injected with meglumine diphosphate, with a total amount of 0.1-0.2ml. Then the radiolucent film was taken immediately, and three positions were selected, including the plain film, the standing film and the lateral film. After that, the mice were sacrificed and the esophagus of the mice was isolated and embedded in sections for pathological and immunohistochemical diagnosis. Finally, the results were compared with the imaging results.

RESULTS: Based on the comparison of imaging and pathological results, we found that most of the esophageal segments with filling defects on esophagography were pathologically diagnosed as esophageal squamous cell carcinoma, and another part were diagnosed as esophageal papilloma. Compared with CT and MRI, esophagography has the advantages of simple operation and less consumable materials.

CONCLUSION: We found that esophagography is a new non-invasive auxiliary diagnostic method for the successful establishment of an orthotopic mouse model of esophageal squamous cell carcinoma.