Z Gastroenterol 2011; 49 - V2_01
DOI: 10.1055/s-0030-1269613

Effects of Radiofrequency Ablation (RFA) in combination with Sorafenib in a 2-Tumor Rat Model of Hepatocellular Carcinoma

C Hora 1, JC Mertens 2, B Saar 3, J Kettenbach 3, M Ledermann 4, S Mertens 2, JF Dufour 4, A Geier 2
  • 1Institute of Clinical Pharmacology and Visceral Research - University of Bern, Bern, Schweiz
  • 2Klinik für Gastroenterologie und Hepatologie, UniversitätsSpital Zürich, Schweiz, Zürich, Schweiz
  • 3Department of Diagnostic Radiology - Inselspital Berne (University Hospital of Berne), Bern, Schweiz
  • 4Institute of Clinical Pharmacology and Visceral Research, University of Berne, Bern, Schweiz

Aims: Radiofrequency ablation (RFA) is a established therapy for hepatocellular carcinoma (HCC). Multitkinase inhibitor sorafenib prolongs survival in advanced HCC. We examined effects of RFA combined with sorafenib in a two-tumor rat model of HCC. Methods: 1mm cubes of Morris Hepatoma cells (MH) were were implanted into the right and left liver lobe of syngeneic ACI rats in four treatment groups. We administered sorafenib (7.5mg/kg/d) or vehicle p.o., starting d 12 after tumor implantation. RFA of the left lobe tumor or sham operation was performed on d 15. Group 1 received vehicle and a sham operation. Group 2 had vehicle and RFA therapy. Group 3 had sorafenib and a sham operation. Group 4 had sorafenib and RFA therapy. Tumor volumetry was done by MRI scans at d 14 and d 20. Animals were sacrificed at two timepoints: d 18 and 30 post-implant (n=10 per group). Angiogenesis (CD31 staining) and hepatic mRNA expression of cyclin E1 and HGF (TaqMan PCR) were analyzed. Results: At d 30, for the unablated right tumors, largest tumor volumes were seen in controls (831±264 mm3). In the RFA-only group, right tumors were significantly smaller (580±129 mm3, p<0.05). Sorafenib alone further reduced tumor growth compared to controls (367±177 mm3, p<0.001) and to RFA-only group (p<0.05). Combined sorafenib and RFA resulted in maximal tumor reduction (282±118 mm3 vs. control, p<0.0001; vs. RFA-only group, p<0.001). Vessel density (/mm2) was markedly increased in the unablated tumor of the RFA-only group even above controls. Sorafenib reduced vessel density in both RFA and sham animals. Cyclin E1 and HGF expression showed similar pattern. Conclusions: RFA and sorafenib alone both result in significant volume reduction of the unablated tumor. In contrast RFA increased vessel density and proliferative gene expression. This data suggest that RFA is eliciting two opposing effects, a pro-proliferative stimulus, counteracted by a putative anti-tumor immunoreaction.

HCC - Radiofreqency ablation - Sorafenib - rat modell