Mesocaval shunt inhibits primary and metastatic hepatoma growth and enhances apoptosis

Abstract

Background: Previous reports indicate that hepatocyte growth factor and other hepatic trophic factors reach the liver presumably by portal venous inflow and stimulate experimental hepatic tumor growth, invasion, and metastasis. This study tests this hypothesis by evaluating whether a mesocaval shunt (MCS) alters hepatic tumor growth, the mitotic rate, apoptosis, and incidence and growth of lung metastasis in rats with implanted hepatoma. Methods: Morris hepatoma (1 × 10 5) cells were implanted intrahepatically in 19 ACl rats. One week after implantation, 10 rats underwent MCS operation and nine controls a sham operation. Rats were killed 21 days after the operation to assess tumor volume, tumor cell mitosis, apoptosis, area of tumor necrosis, pulmonary metastases and percentage of lung tumor area. Results: Mesocaval shunt induced a significant increase in the rate of tumor apoptosis (25 ± 5 v 14 ± 6, P < .01) and the percentage of area of tumor necrosis (29% ± 17% v 13% ± 8%, P < .05), a decreased tumor volume (839 ± 1,195 v 2,909 ± 2,572, P < .05), a reduction in tumor mitosis (70 ± 28 v 93 ± 11, P < .05) and decreased percentage area of pulmonary metastatic tumor (9.8 ± 6.8 v 18.8 ± 14, P < .05). Conclusion: These observations show that growth of intrahepatic tumor is influenced by portal venous inflow and suggest that MCS or other methods of regulating portal vein flow may be useful as adjunctive therapy in the treatment of advanced hepatoma.