Novel Concept of Electrocoagulation and Tumor Cell Implantation: Creation of Minimally Invasive Orthotopic Murine Model of Pancreatic Cancer.

Abstract

Background: Orthotopic murine models of pancreatic cancer represent an important tool for evaluating treatment strategies. Several genetically modified mouse tumors and xenograft models have been reported. Genetic models have unpredictable growth and variable waiting period, while orthotopic models are operative ones, difficult to create and result in irregular metastasis. There is a constant endeavor to create an orthotopic model which replicates the human disease process.

Study design: Orthotopic human pancreatic tumors were induced in 20 SCID mice using a novel technique. Low dose electrocoagulation of pancreas under laparoscopic guidance (using Coloview-mouse colonoscope) with thin electrode, followed by injection of 0.1 cc BxPC3 pancreatic cancer cells was done (n = 12, study group). Control mice underwent electrocoagulation alone (n = 4, group 1) and tumor cell injection alone (n = 4, group 2). Mice were evaluated for tumor growth and metastasis by necropsy (4 and 8 weeks for experimental group; 8 weeks for control group).

Results: Tumors were detected in 11/12 mice in experimental group, 1/4 in control group 2, and none in control group 1. Over time there was an increase in tumor growth, tumor volume, lymphovascular invasion of pancreas, with metastasis to lymph nodes and surrounding organs.

Conclusion: We report a novel concept of tumor cell implantation at site of electrocoagulation of pancreas. Combined with the minimally invasive technique, yields a replicative orthotopic murine model of pancreatic cancer. Our model is minimally invasive, easy to create, and overcomes the limitations of the existing models while questions the possibility free floating tumor cell implantation at resection site.