The efficacy and toxicity of Oxaliplatin in rabbit inoculated VX2 hepatic cancer during isolated hepatic perfusion with retrograde outflow / 中华普通外科杂志

ABSTRACT

Objective To study the anti-tumor effect and liver toxicity of Oxaliplatin (L-OHP)from different outflow tracts, we implemented isolated perfusion on rabbit VX2 tumor model with L-OHP.Methods In this study, 60 rabbits in which VX2 liver cancer were established were randomly divided into three groups ( A = B = C = 20). Group A and B were taken isolated hepatic perfusion with 5 mg/kg L-OHP,while group C was normal control, which was taken isolated hepatic perfusion without L-OHP. Perfusion fluid flowed through the hepatic veins in group A, while in group B and C perfusion fluid flowed through the portal vein. Blood biochemistry、liver histopathology 、vascular endothelial growth factor (VEGF) expression and hepatocyte apoptosis index (AI) in the postoperative 6th and 12th hour were examined. L-OHP concentration was measured during the perfusion with RP-HPLC in group A and B. Results Serum ALT、AST rose significantly in all three groups in the 6th and 12th hour postoperatively, and that in group A was higher than either group B or C. Differences in serum ALT、AST level between group A and B, B and C, A and C were all statistically significant (tALT = 2. 328、tALT =7. 116、tALT =3. 124,P ＜ 0.05;tAST =2.547、tAST =4. 710、tAST = 2. 238, P ＜ 0. 05 ). The differences of L-OHP concentration in the liver and systemic circulation between group A and B was statistically significant(t =3.091, P ＜0. 05;t =2. 778,P ＜0. 05),however the difference between group A and B of L-OHP concentration in the tumor tissue and outflow tract was not statistically significant( t = 1. 461, P ＞ 0. 05; t = 0. 223, P ＞ 0. 05 ). Hepatic pathology in group A was more serious than that in group B in the 12th hour postoperatively. The levels of VEGF expression in liver tumor tissue in postoperative 12th hour, in group A and B were significantly lower comparing with group C (tAC =2.728, P ＜ 0.05;tBC =3.397,P ＜0.01). Between group A and B, the difference was not statistically significant ( t = 0. 591, P ＞ 0. 05 ). Differences in hepatocyte apoptosis index ( AI ) in the postoperative 12th hour between group A and C, A and B, B and C were all statistically significant( tAB=3. 689, P ＜ 0. 01 ;tAC = 5. 067, P ＜ 0. 01 ;tBC = 2. 607, P ＜ 0. 05 ), and with that in group A being higher than either in group B or C. Conclusions L-OHP had a significant anti-tumor effect in isolated hepatic perfusion; Chemotherapy infusion fluid flowing through the portal vein retrogradely was a more complete and safer way of regional chemotherapy than antegrade flowing through the hepatic vein.