DEVELOPMENT OF A RAT MODEL FOR ORTHOTOPIC LIVER-TRANSPLANTATION FOR HEPATOCELLULAR-CARCINOMA

Background. Surgical resection is of limited benefit in hepatocellular carcinoma accompanied by severe liver cirrhosis or multicentric hepat ic cancer. The long-term survival of patients with advanced hepatocell ular carcinoma after transplantation is quite poor. We have studied th e characteristics, natural course, and cause of diethylnitrosamine-ind uced liver cancer in rats and have shown it to be a good model of live r cancer in human beings. Therefore we performed orthotopic liver tran splantation (OLT) in rats with diethylnitrosamine-induced liver cancer to study the patterns of recurrence. Methods. Diethylnitrosamine 100 parts per million in drinking water was administered daily for 4 month s to male inbred. LEW rats. A laparotomy was performed 220 or 134 days after commencing the oral diethylnitrosamine to confirm the induction of cancer confined grossly to the liver The livers were resected, and orthotopic transplantation with livers of normal LEW rats was perform ed. Results. By day 150 all the rats in the non-OLT group died of intr aabdominal hemorrhage caused by spontaneous rupture of liver cancer (m ean survival time +/- SD, 138.2 +/- 5.3 days; n = 14). However, the OL T (day 120) group recovered their body weight comparatively early afte r transplantation and survived a maximum of 218 days until death from recurrence (203.8 +/- 21.3 days; n = 4). A significant extension in su rvival time was observed (p< 0.01). In autopsies performed at the time of death, metastatic liver cancer was observed in the transplanted li vers with two showing metastases to the lung: The cause of death was c ancer in all the rats. However, the OLT (day 134) group all died of ma jor complications of severe pneumonia and disseminated intravascular c oagulation within 2 weeks of OLT (141.3 +/- 5.0 days; n = 4). Conclusi ons. After liver transplantation to rats with hepatocellular cancer co nfined to the liver, recurrence was observed at a comparatively early stage in all transplant recipients. Although a significant prolongatio n of survival was noted they all died of cancer. The timing of transpl antation is also an important factor. This experimental liver transpla ntation model of progressive rat liver cancer will be useful in the st udy of primary liver cancer in human beings.