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As in other tumors, the assessment of microvessel density (MVD) in hepatocellular carcinoma (HCC) may be essential to perform an effective anti-angiogenic therapy for this tumor. The relationship between vascular endothelial growth factor (VEGF) and MVD of HCC as well as the surrounding liver remains to be elucidated. In 71 patients who had undergone curative hepatic resection for HCC, MVD and VEGF expressions were evaluated for HCC and the liver by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and/or immunostaining. The intensity and extent of VEGF immunoreactivity were evaluated using a computer image analyzer-cell analysis system (CAS). Angiographic data were re-evaluated and compared with MVD in 50 tumors. Tumoral MVD was significantly correlated with tumor capsule formation (t test, P ‫؍‬ .0016). Small HCCs (I2 cm) had a significantly lower MVD compared with moderate-sized HCCs (2-5 cm) (t test, P ‫؍‬ .016), and the MVD of large HCCs was relatively lower than that of moderate tumors. Tumor vascularity on angiography was not correlated with the MVD. Neither VEGF mRNA levels nor protein expression in HCC were correlated with the tumoral MVD or any histopathological features of the tumor. However, cirrhotic livers had significantly higher MVD and VEGF expressions compared with noncirrhotic livers (t test, P ‫؍‬ .0015 and P ‫؍‬ .047, respectively). Only the MVD of tumor was significantly correlated with intrahepatic recurrence (t test, P ‫؍‬ .0048) and disease-free survival (DFS) rates (log rank test, P ‫؍‬ .0035). Moreover, the MVD was an independent predictor for DFS by multivariate analysis ( 2 test, P ‫؍‬ .03). In conclusion, the MVD in HCC may be involved in the dismal prognosis of this tumor, and VEGF may be associated with the angiogenic process of the cirrhotic liver, but not with the angiogenesis of HCC. (HEPATOLOGY 1998;27:1554-1562.)Angiogenesis is implicated in cancer development, progression, growth, and metastasis.

The results of hepatic resection in 229 patients with HCC were analyzed. Child's class, BSP test, and blood loss during surgery were good predictors for operative death. The 5- and 10-year survival rates were 26.4% and 19.4%, respectively. Age, liver cirrhosis, tumor size, and postoperative chemotherapy were prognostic factors. Multidisciplinary approach with liver resection, postoperative chemotherapy, and liver transplantation will be a realistic direction for the surgical treatment of HCC in future.

In the treatment of HCC without cirrhosis, major hepatectomy is advocated to prevent early recurrence. Liver transplantation may be required for patients with HCV infection.

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