Establishment and comparison of two rat models of liver transplantation for hepatocellular carcinoma

Objective To compare the validity and reliability of diethylnitrosamine (DEN)-induced and intrahepatic-tumorimplanted hepatoma related to tumor recurrence after liver transplantation for hepatocellular carcinoma.Method A small and superficial incision into the liver of SD rats was made,and 0.5-1.0 mm cube of walker-256 carcinosarcoma fragments was implanted into the liver incision.At week 2,Syngeneic OLT was performed with the cuff technique without rearterilization.Hepatoma was also induced by DEN administered continuously through the drinking water,in which survival and metastasis were analyzed.Furthermore,the comparisons were performed related to formation of tumor,postoperative survival,tolerability of immunosuppression and tumor recurrence for OLT for DEN-induced or intrahepatic-implanted hepatoma.Results The presence of solitary tumor was 100％ at week 2 in the intrahepatic tumor implantation (IHTI) model,and the OLT of recipients was done.The 3-week survival rate after OLT for IHTI was 84％ (21/25),and the incidence of lung metastases was 0 (0/5),20％ (1/5),60％ (3/5) and 67％ (4/6) at week 4,5,6,7 respectively.The tumor from DEN was found in 1/10,8/10,10/10,and 0/10 in 75-day,95-day,115-day and 75-day+ CsA groups,respectively.A significant difference in postoperative survival was observed between group 75-day and 95-day group (log rank =5.348,P =0.021) ; also between 75-day group and 115-day group (log rank =9.820,P =0.002).No recurrence was presented in the transplants from DEN.Conclusion Hepatoma induced by DEN is not suitable to study recurrence after OLT for HCC,due to highly variable outcome from same carcinogenesis pattern.The value of IHTI model for this purpose was greatly associated with biological behaviors and tumor-initiating ability of cancer cells. Key words: Rats;  Liver transplantation;  Animal model;  Hepatocellular carcinoma