The Pathological Observation And Expression Of VEGF And MVD After RFA In Rabbit Hepatic VX2 Tumor

Liver cancer is one of the most common diseases in human due to its high morbidity, mortality and increasing incidence worldwide. Although hepatic resection and transplantation have been considered as the main therapies for HCC, the vast majority of patients are not eligible when this tumor is detected. Only about 20% of HCC cases are resectable.For the unresectable liver cancers,the local treatment combined with comprehensive treatments is very important.In recent years, minimally invasive treatments(MIT) have been carried out,including radiofrequency ablation (RFA), microwave, freezer, high-intensity focused ultrasound, percutaneous ethanol injection ( PEI ) and transcatheter arterial chemoembolization(TACE).RFA has gradually developed into the more mature and effective local treatment because of its several advantages, such as definitive therapeutic effect, minimal invasiveness, repeatability, safety, and shorter hospitalization. A sufficient safety margin can prevent local tumor recurrences. At present, residual tumor is one of the main obstacles that greatly hinders the effectiveness of RFA for HCC. As a result, nests of viable tumor cells remain in the clefts between the incompletely fused coagulation zones. The residual carcinoma may exhibit an aggressive phenotype and unfavorable prognosis.Many domestic and foreign scholars do a lot of research on the mechanisms of metastasis and recurrence of hepatocellular carcinoma,especially the angiogenesis of hepatocellular carcinoma.It is believed that a large number of tumor angiogenesis is the one of the main factors of metastasis and recurrence. Many tumors can secrete angiogenic factors, among which vascular endothelial growth factor (vascular endothlial growth factor, VEGF) play an important role in triggering metastasis. Based on analysis of the risk factors, we establish rabbit model of remnant carcinoma after RFA therapy , and to observe pathomorphological changes of remnant carcinoma in different time and in different ablation zone for the purpose of providing a theoretical basis for clinical treatment.Objective To evaluate the effect of radiofrequency ablation(RFA) in treating liver VX2 tumor in rabbits, and to investigate the effect on malignant potency including Microvessel density(MVD) and vascular endothelial growth factor (VEGF). Methods New Zealand White rabbits were randomly divided into six groups before they were implanted liver VX2 tumors, RFA was performed by laparotomy on VX2 tumors. Treatment was performed with an energy output of and was given 12 minutes. Rabbits in each group was killed and before RFA and 1 d , 3 d , 1 w , 2 w and 3 w after operation , respectively. The morphological changes of the tumor and hepatic tissue were also investigated under light microscope. Vascular endothelial growth factor (VEGF) and microvessel density(MVD) expression were examined by immunohistochemistry.Results VX2 tumors were grown in the livers of 46 rabbits,the occurrence rate of tumor was 95%. 2 cases of rabbit hepatic VX2 carcinoma died at 2 weeks.And there were 2 rabbits were observed tumor metastasize in the abdomen. The tumors located in the left liver lobes were 1.8 to 2.0 cm in diameter. The VX2 tumors seemed to assume similar spherical,no obviously peplos, the diameter was 1.8 to 2.0 cm,there was obvious gray necrosis in the center of the tumor.The HE staining showed the tumor cells were arranged illregularly with invasive growth potential before RFA. The expression of VEGF and MVD in the coagulation zone and central area of the RF-induced ablation zone decreased significantly. The expression of VEGF and MVD in the RF-induced ablation zones increased obviously after RFA. The differences were significant in the RF-induced ablation zones compared with the coagulation zone and central area of the RF-induced ablation zone,P<0.05. Conclusions The method of making rabbit hepatic VX2 tumors model is simple,and the occurrence rate is very high, and the model was fit for RFA. There were residual hepatic VX2 tumors in the RF-induced ablation zones. and the residual hepatic VX2 tumors could facilitate its rapid progression through inducing over expression of several molecular factors, such as VEGF.