An implantable rat liver tumor model for experimental transarterial chemoembolization therapy and its imaging features.

AIM: To establish an ideal implantable rat liver tumor model for interventional therapy study and examine its angiographic signs and MRI, CT features before and after embolization. METHODS: Forty male Wistar rats were implanted with Walker-256 tumor in the left lateral lobe of liver. Digital subtraction angiography (DSA) and transarterial chemoembolization were performed on day 14 after implantation. Native computer tomography (CT, n=8) and native magnetic resonance (MR, n=40) were performed between the day 8 and day 21 after implantation. The radiological morphological characteristics were correlated with histological findings. RESULTS: Successful implantation was achieved in all forty rats, which was confirmed by CT and MRI. MR allowed tumor visualization from day 8 while CT from day 11 after implantation. The tumors were hypodensity on CT, hypointense on MR T1-weighted and hyperintense on T2-weighted. The model closely resembled human hepatocarcinoma in growth pattern and the lesions were rich in vasculature on angiography and got its filling mainly from the hepatic artery. Before therapy, tumor size was 211.9+/-48.7 mm(3). No ascites, satellite liver nodules or lung metastasis were found. One week after therapy, tumor size was 963.6+/-214.8 mm(3) in the control group and 356.5+/-78.4mm(3) in TACE group. Ascites (4/40), satellite liver nodules (7/40) or lung metastasis (3/40) could be seen on day 21. CONCLUSION: Walker-256 tumor rat model is suitable for the interventional experiment. CT and MRI are helpful in animal optioning and evaluating experimental results.

Influence of transarterial chemoembolization on angiogenesis and expression of vascular endothelial growth factor and basic fibroblast growth factor in rat with Walker-256 transplanted hepatoma: an experimental study.

AIM: After transarterial chemoembolization (TACE), the residual cancer cells are under extensive hypoxic or even anoxic environment. Hypoxia can lead to adaptive responses. For example, angiogenesis will help these cells survive. In this study, we examined the effect of TACE on angiogenesis and expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) and to assess their relevance to Walker-256 transplanted hepatoma. METHODS: Male Wistar rats were inoculated with Walker-256 tumor in the left lobe of liver. Angiography and transarterial chemoembolization were performed at d14 after transplantation. Sixty rats bearing walker-256 transplanted hepatoma were randomly divided into control group, arterial infusion group and TACE group. Each group consisted of twenty rats. Normal saline, 5-Fu, 5-Fu and lipiodol were infused through hepatic artery respectively. Two weeks after the infusion, staining of factor VIII, VEGF and b-FGF was performed by immunohistochemistry method in routine paraffin-embedded sections. Microvessel density (MVD) was counted in endothelial cells with positive factor VIII. Their expression levels were analyzed in conjunction with the pathologic features. RESULTS: While a smaller tumor volume was found in TACE group (F=37.818, P<0.001), no statistical differences between MVD and expression of VEGF and b-FGF were found among the 3 groups. MVD of the control group, chemotherapy group and chemoemoblization group was 80.84+/-24.24, 83.05+/-20.29 and 85.20+/-23.91 (F=0.193, P=0.873), respectively. The positive expression of VEGF and b-FGF was 75%, 75%, 85% (chi2=0.449, P=0.799) and 30%, 25%, 30% (chi2=0.141, P=0.922), respectively. Statistical analysis revealed a positive correlation between the expression of VEGF and MVD (r=0.552, P<0.001). CONCLUSION: There has been little influence of lipiodol chemoembolization on the formation of tumor angiogenesis, but the development of neovascularization and expression of VEGF play important roles in establishment of collateral circulation and reconstruction of blood supply of residual cancer tissue.

Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level.

AIM: To investigate the expression level of plasma vascular endothelial growth factor (P-VEGF) in patients with hepatocellular carcinoma (HCC) and its relationship with the clinicopathologic characteristics, and to examine the changes of P-VEGF in the course of transcatheter arterial chemoembolization (TACE). METHODS: Peripheral blood samples were taken from 45 HCC patients before and 1, 3, 7 d, and 1 mo after TACE. Plasma VEGF level was measured with the quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Twenty patients with benign liver lesions and 17 healthy control subjects were also included in this study. RESULTS: Plasma VEGF levels in HCC patients were significantly elevated as compared to those in patients with benign liver lesions (P = 0.006) and in the normal controls (P = 0.003). Significant differences were observed when P-VEGF was categorized by tumor size (P = 0.006), portal vein thrombosis (P = 0.011), distant metastasis (P = 0.017), arterial-portal vein shunting (P = 0.026), and International Union Against Cancer (UICC) TNM stage (P = 0.044). There was no correlation between plasma level of VEGF and the level of alpha fetoprotein (alpha-FP) (r = 0.068, P = 0.658) and weakly correlated with the number of platelets (r = 0.312, P = 0.038). P-VEGF levels increased significantly and reached the peak value on the first day after TACE, and then decreased gradually. The change rate of P-VEGF concentration (one month post-TACE/pre-TACEX100%) was correlated with the retention rate of lipiodol oil (r s = 0.494, P = 0.001) and the tumor volume change (r s = 0.340, P = 0.034). The patients who achieved a partial or complete response to TACE therapy showed significantly less pre-treatment P-VEGF than those nonresponders (P = 0.025). A high pre-therapeutic P-VEGF level was associated with poor response to treatment (P = 0.018). CONCLUSION: A high pre-treatment P-VEGF level is a useful marker for tumor progression, especially for vascular invasion. TACE increases the level of P-VEGF only temporarily which may be associated with tumor ischemia. P-VEGF may be useful in predicting treatment response, monitoring disease course after TACE and judging the effect of different TACE regimens.