Effect of Transcatheter Hepatic Arterial Embolization on Angiogenesis in an Animal Model

Abstract

OBJECTIVES: Transcatheter arterial embolization (TAE) is used for the treatment of patients with malignant liver tumors. However, the proangiogenesis effect of TAE-associated hypoxia has not been adequately studied. The goal of this study was to determine angiogenic activity in tumors subjected to TAE by evaluating the tumor microvessel density (MVD). MATERIALS AND METHODS: Mammary cancer 13762 NF tumor cells were inoculated into the livers of male Sprague-Dawley rats. TAE was performed 12-14 days after tumor inoculation. Rats were divided into 4 groups on the basis of treatment type. Control group animals (n = 16) were subjected to sham TAE without polyvinyl alcohol (PVA) particles. Animals in the other 3 groups were subjected to TAE with 1 (n = 11), 2 (n = 8), or 3 (n = 10) mg of PVA particles. Rats were killed 3-6 hours or 2 or 3 days after embolization, and the liver tumor tissues were dissected and frozen in liquid nitrogen. Tumor tissue slides were prepared, stained with CD-31, and evaluated for MVD. Blood samples collected just before sacrificing the animals were used to measure serum vascular endothelial growth factor (VEGF) levels. RESULTS: Tumors treated with TAE showed varying degrees of central necrosis with residual viable tumor cells in the periphery. Tumor MVD in animals treated with TAE was significantly higher than that in the control group (23.6 versus 17.5; P = 0.001). Although the MVD in animals treated with TAE using 1 mg of PVA was higher than that in the control group, this difference was not statistically significant. TAE using 2 mg of PVA resulted in a significant increase in tumor MVD (25.9 versus 17.5; P = 0.007). Use of 3 mg of PVA did not result in any further increase in MVD. There was a significant increase in tumor MVD in the animals killed 2 or 3 days after TAE compared with the control group (24.5 versus 17.5; P = 0.002). The animals treated with TAE showed a statistically significant increase in VEGF levels compared with the control group. CONCLUSIONS: TAE of hepatic tumors results in the stimulation of angiogenesis in the residual viable tumor, which could have an adverse effect on the therapeutic efficacy of TAE.