3:45 PMAbstract No. 44 - Thermal ablation induces accelerated intrahepatic tumor growth in an orthotopic model of hepatocellular carcinoma

Abstract

Previous clinical studies have shown that aggressive intrahepatic recurrence may occur following thermal ablation of HCC. However, there are currently no experimental models for studying thermal ablation-induced accelerated intrahepatic tumor growth. The aim of the present study was to test the hypothesis that liver thermal ablation induces accelerated local versus distant intrahepatic tumor growth in an orthotopic model of hepatocellular carcinoma. In an IACUC-approved study, 3x106 N1S1 rat HCC cells were inoculated into the median hepatic lobe of Sprague-Dawley rats. The tumor-cell bearing rats were randomized to immediate laser thermal ablation of the median hepatic lobe (local intrahepatic group) at 3W x 60s (N=6), 3W x 90s (N=6) or sham laser ablation (N=7). The experiment was repeated with inoculation of N1S1 cells into the median hepatic lobe and laser thermal ablation of the left lateral hepatic lobe (distant intrahepatic group) at 3W x 90s (N=7) or sham laser ablation (N=7). Tumor growth was monitored by T2-weighted magnetic resonance imaging (MRI) at 4, 10, 14 and 18 days post-ablation. Tumor volumes calculated from MR images were compared by ablation dose (sham v. 60s v. 90s) and intrahepatic tumor site (local v. distant). Thermal liver ablation induced accelerated growth of local intraheptatic tumor compared to sham ablation by day 18 in a dose dependent manner (1363mm3±361v. 3102 mm3±463 v. 3538mm3±667; sham v. 60s v. 90s; p<0.05; p<0.01). Thermal liver ablation did not induce accelerated growth of distant intrahepatic tumor compared to sham (2023mm3±666 v. 3256 mm3±632; p=0.2). These data suggest that thermal ablation of liver induces accelerated growth of intrahepatic tumor in a thermal-dose dependent manner. Moreover, local intrahepatic growth mechanisms may play a greater role than systemic growth mechanisms in ablation-induced accelerated tumor growth in the liver. Further pre-clinical studies in this model may help to identify critical growth factors as candidate therapeutic targets to prevent thermal-ablation induced accelerated tumor growth.