Efficacy of intra-hepatectomy 5-FU on recurrence and metastasis of human hepatocellular carcinoma in nude mice

A novel intra-operative chemotherapy nude mouse model for human hepatocellu lar carcinoma (HCC) has been developed. Intra-peritoneal (i.p.) administrat ion 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, t ermed intra-hepatectomy chemotherapy (IHC), significantly prolonged animal survival compared with pre-operative 5-FU, neoadjuvant therapy, 5-FU post-o perative adjuvant therapy, surgery alone, 5-FU without surgery, and the unt reated control, The median survival of the intra-operative 5-FU-treated gro up 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 neoad juvant 5-FU treatment had died, 60% of the animals in the IHC group were st ill alive (p < 0.011). Survival of all other treatment groups, including 5- FU without surgery, surgery atone, and adjuvant post-operative chemotherapy , was not significantly different from the untreated control group. Five an imals in the IHC group were free of tumor when sacrificed at day 150 post-s urgically, While 100% of animals in the control group had lymph nodes drain ing the liver involved with metastases, only 20% of animals in the IHC grou p had lymph node metastases. These data suggested that IHC therapy increase d survival by preventing metastases of cancer cells not removed in the live r resection procedure. The results of this study indicate that IHC therapy for resection of HCC should be investigated clinically (C) 2001 Wiley-Liss, Inc.