A novel intra-operative chemotherapy nude mouse model for human hepatocellular carcinoma (HCC) has been developed. Intra-peritoneal (i.p.) administration of 5-fluorouracil (5-FU) was begun 2 hr before hepatic resection of HCC and then continued post-operatively for 4 consecutive days. This regime, termed intra-hepatectomy chemotherapy (IHC), significantly prolonged animal survival compared with pre-operative 5-FU, neoadjuvant therapy, 5-FU post-operative adjuvant therapy, surgery alone, 5-FU without surgery, and the untreated control. The median survival of the intra-operative 5-FU-treated group was 127 days compared with 78 days for the neoadjuvantly-treated animals and 53 days for the control group (p<0.006). When all animals with neoadjuvant 5-FU treatment had died, 60% of the animals in the IHC group were still alive (p<0.011). Survival of all other treatment groups, including 5-FU without surgery, surgery alone, and adjuvant post-operative chemotherapy, was not significantly different from the untreated control group. Five animals in the IHC group were free of tumor when sacrificed at day 150 post-surgically. While 100% of animals in the control group had lymph nodes draining the liver involved with metastases, only 20% of animals in the IHC group had lymph node metastases. These data suggested that IHC therapy increased survival by preventing metastases of cancer cells not removed in the liver resection procedure. The results of this study indicate that IHC therapy for resection of HCC should be investigated clinically.
Copyright 2001 Wiley-Liss, Inc.