Liver Transplantation Improves Survival of Rats Bearing Hepatoma-3924A

Abstract

There was interest in developing a rat model of hepatocellular carcinoma with tumor dissemination that would respond to liver transplantation. Thus, a model of intrahepatic hepatoma implantation with micrometastases was developed by modifying a previously reported technique in the ACI rat. The pattern of tumor growth permits surgical resection with liver transplantation if done early in the course of disease. In addition, this model results in a reproducible rate of pulmonary metastatic disease. The pulmonary metastatic rate (number of rats developing pulmonary metastases) was 45.5% (n= 11) 2 weeks following intrahepatic tumor implantation and rose to 100% at the fifth week (n= 7). To examine the long-term outcome of animals with tumor, 46 animals were followed until death or 100 days after tumor implantation. Of these animals, 67.4% died from tumor within 100 days, all with pulmonary metastases. Several of the animals that were followed long term had advanced liver tumor as well, with intraperitoneal spread and ascites. To evaluate the effect of orthotopic liver transplantation (OLTX) in this model, syngeneic OLTX was performed 16 days after intrahepatic tumor implantation (n= 11). OLTX improved the 100-day survival of the recipients from 32.6% (control group) to 80.0% (P< 0.05). None of the long-term survivors had evidence of tumor on postmortem examination. The mechanisms responsible for decreased metastases following syngeneic liver transplantation are being investigated. The influence of immunosuppression, more advanced stage of tumor at the time of OLTX, and chemotherapeutic agents on this survival benefit could be be investigated with this model.