Toxicity and efficacy of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma (Review).

The prognosis of advanced hepatocellular carcinoma (HCC) remains poor, particularly for patients with portal vein tumor thrombosis. Chemotherapy is one of the most significant treatment options for patients with advanced HCC not indicated for hepatic resection, percutaneous ablation and transcatheter arterial chemoembolization. Systemic chemotherapy does not play a central role in the treatment of HCC due to the issue of low sensitivity for chemotherapeutic agents and the difficulties in administering a sufficient dose due to chronic liver dysfunction. Therefore, patients with advanced HCC are usually treated with hepatic arterial infusion chemotherapy (HAIC), which is increasingly used as an approach to advanced HCC in Japan. HAIC provides moderate therapeutic efficacy and survival benefit with substantially tolerable toxicity profiles in patients with advanced HCC.

Antifibrotic effect of edaravone in rat liver cirrhosis induced by dimethylnitrosamine.

Edaravone (EDA), a newly synthesized free radical scavenger, has shown excellent results in the treatment of stroke. An overproduction of reactive oxygen species (ROS) causing oxidative DNA damage has been accounted as a major factor causing liver injury and fibrosis. Therefore, we examined its effect of EDA in rat model of liver cirrhosis induced by dimethylnitrosamine (DMN). Ten rats (DMN-group) were injected intraperitoneally with DMN (10 microg/g body weight) alone and another ten rats (EDA-group) were injected intraperitoneally with EDA (10 mg/kg body weight) 2 h after being injected with DMN. Both groups underwent their injection regimen three times a week for 4 weeks, after which the rats were sacrificed and their liver tissue sections were stained with Azan-Mallory for quantitative analyses of fibrosis development, using soft imaging and a previously published scoring system. Additionally, these sections were immunohistochemically stained using an antibody against alpha-smooth muscle actin (alpha-SMA). The total-bililubin in the EDA-group was found to be lower than that in the DMN-group. Quantitive analysis of liver fibrosis showed that the fibrotic area of the EDA-group was significantly smaller than that of the DMN-group. Additionally, the number of alpha-SMA positive cells in the EDA-group were significantly lower than that in the DMN-group. This study showed that EDA reduces liver fibrosis in a rat of cirrhosis induced by DMN. These data suggest that the reduction of liver fibrosis by EDA may be induced by the suppression of activated hepatic stellate cells.

Adjuvant chemotherapy with tegafur/uracil administration after transcatheter arterial chemoembolization for advanced hepatocellular carcinoma.

Although transcatheter arterial chemoembolization (TACE) is considered to be an effective treatment for advanced hepatocellular carcinoma (HCC), it is difficult to achieve complete necrosis by TACE alone due to incomplete embolization and tumor angiogenesis. Recent studies have shown that tegafur/uracil (UFT) inhibits tumor angiogenesis in several cancer types. Therefore, this study was conducted to test the efficacy and toxicity of the UFT administration after TACE in advanced HCC. Thirty patients with HCC who had been treated with TACE alone more than three times and had a recurrence within 6 months were enrolled. All of the patients were treated with TACE and 28 patients were randomly assigned to the UFT (UFT 300 mg/day, three days after TACE, n=14) and control groups (n=14). The primary end point was the time to treatment failure (TTF) and the secondary end points were mainly the response rate and toxicity. Administration and observation were continued up to 6 months after TACE unless local recurrence was detected or serious adverse events developed. The median TTF in the control group was 87 days, whereas in the UFT group it was 127 days, thus significantly prolonged as compared to the control group (P=0.0016). Moreover, the overall response rate (35.7%) in the UFT group was significantly higher than that in the control group (0%). As for toxicity, only 4 patients in the UFT group developed grade 1-2 toxicities such as ascites. Serious complications by TACE were not observed in either group. Notably, there were no increases in the serum VEGF levels in the UFT group whereas those in the control group increased significantly. In conclusion, UFT administration after TACE was an effective treatment and showed no severe adverse events. This regimen may have an adjuvant role and antiangiogenic function in advanced HCC.

Rapid intrahepatic tumor seeding after percutaneous ethanol injection therapy for hepatocellular carcinoma.

A 73-year-old man with hepatocellular carcinoma (HCC) had been treated repeatedly with transcatheter arterial embolization (TAE) and percutaneous ethanol injection therapy (PEIT) since 2000. HCC recurrence near the intrahepatic left portal vein was treated by PEIT in 2004. The patient complained of fatigue and upper abdominal pain 28 days later. Abdominocentesis and abdominal computed tomography demonstrated rupture of the recurrent HCC and multiple intrahepatic recurrences. We successfully performed emergency TAE, but the patient died of liver failure. Rapid seeding of multiple intrahepatic tumors after PEIT is a rare event, but such a possibility must be kept in mind.