High circulating endothelial progenitor levels associated with poor survival of advanced hepatocellular carcinoma patients receiving sorafenib combined with metronomic chemotherapy.

OBJECTIVES: We examined whether circulating endothelial progenitor (CEP) and circulating endothelial cell (CEC) levels had associations with the survival of patients who received antiangiogenic therapy for advanced hepatocellular carcinoma (HCC). METHODS: Patients with advanced HCC were enrolled into a phase II trial evaluating a combination of sorafenib and metronomic chemotherapy with tegafur/uracil as first-line systemic therapy. CEPs and CECs were enumerated with six-color flow cytometry at baseline, 2 weeks, and 4 weeks after treatment and analyzed for their associations with treatment outcomes along with other clinicopathologic factors. RESULTS: Forty patients were enrolled. Baseline CEP and CEC levels were not associated with tumor stages, α-fetoprotein levels, or macrovascular invasion. By univariate analysis, a high baseline CEP level was a significant predictor of poor progression-free survival (PFS) and overall survival (OS) (p = 0.02 and p = 0.004, respectively). The high baseline CEP level remained an independent, significant predictor of poor PFS [hazard ratio (HR) 1.953, p = 0.049] and OS (HR 2.512, p = 0.004) in multivariate analysis. On the other hand, the baseline or posttreatment CEC levels were not associated with PFS or OS. CONCLUSION: High baseline CEP levels were associated with poor survival in patients with advanced HCC receiving sorafenib-based antiangiogenic combination therapy.

Boron-lipiodol: a potential new drug for the treatment of liver tumors.

BACKGROUND: Boron neutron capture therapy (BNCT) is a form of radiation therapy and has been proposed for the treatment of some malignancies with encouraging results. However, none of them has ever been applied to liver malignancy. The purpose of this study was to evaluate the potential of boron-lipiodol (B-lipiodol) for the treatment of VX2 liver tumor via BNCT. MATERIALS AND METHODS: Twelve New Zealand rabbits were randomly separated into two groups: lipiodol and boron-lipiodol groups. The rabbits were anesthetized, a midline incision was made and the left lobe of the liver was injected with 0.1 ml of VX2 tumor cells. After the tumor reached 2-3 cm in diameter, the rabbits were anesthetized and 0.5 ml of boron-lipiodol was injected into the hepatic artery via an angiocatheter. Liver function tests and renal function tests were performed before, at 12 hours, 24 hours, 48 hours and 7 days after injection of drugs in both groups. The concentration of boron in various tissues was determined on the 7th day after injection. RESULTS: Liver function was abnormal at 12 hours after injection, and then gradually returned to normal at 7 days, indicative of acute temporary hepatic damage. As for the renal function, no significant change was noted in either group. The boron level was 49.7 ppm in tumor and 6.31 ppm in the healthy liver 7 days after injection of B-lipiodol. The ratio of boron concentrations between the tumor and the normal liver tissue was 7.87. As for blood and other organs including spleen, heart and kidney, the concentration of boron was low. In the lipiodol group, the boron concentrations in tumor and various organs were low. CONCLUSION: The high concentration of boron after intra-arterial injection of B-lipiodol can be used for neutron capture therapy. B-lipiodol has potential for the treatment of liver malignancy.