Impact of surgical treatment after sorafenib therapy for advanced hepatocellular carcinoma.

BACKGROUND: For advanced hepatocellular carcinoma (HCC), surgical treatment after sorafenib induction has rarely been reported. We examined the survival benefit of additional surgical treatment in sorafenib-treated patients. METHODS: Thirty-two advanced HCC patients were given sorafenib from July 2009 to July 2012, and we statistically analyzed the relevant predictive factors of the long-term survival. The institutional review board of Kumamoto University Hospital approved this study (Approval number 1038). RESULTS: The median duration of sorafenib administration was 56.5 days (range 5-945). The cumulative overall survival rate was 44.6, 33.4, 26.0 and 17.8% at 1, 2, 3 and 5 years, respectively. The median survival time was 11.2 months. A survival of more than 3 years after the initiation of sorafenib induction was observed in seven patients, five of whom were subjected to additional surgical intervention. Additional surgery was the most significant factor predicting a survival exceeding 3 years (P < 0.0001) and represents an independent prognostic factor [hazard ratio (HR) 0.07; P = 0.01], followed by the total dose of sorafenib. The surgical interventions comprised two hepatic resections ± radiofrequency ablation, two radiofrequency ablations and one lung resection. CONCLUSIONS: A long-term survival might be obtained for select HCC patients given adequate additional surgical treatment, even after sorafenib induction.

Oral branched-chain amino acid granules improve structure and function of human serum albumin in cirrhotic patients.

BACKGROUND AND AIMS: The aim of this study was to evaluate structural and functional alterations of human serum albumin (HSA), with a special focus on the oxidized and reduced forms, in patients with chronic liver disease. We also investigated whether oral branched-chain amino acid (BCAA) supplementation could induce structural changes and improve the functions of HSA. METHODS: The proportion of reduced and oxidized HSA was determined in 16 healthy controls and in 20 chronic hepatitis and 100 cirrhotic patients with stable conditions. To evaluate the functional properties of HSA, this study focused on the antioxidant and binding functions. The radical scavenging activity and binding ability of purified HSA were measured in 68 participants. After BCAA administration for 6 months, 29 patients were evaluated for HSA structural changes, with 19 out of the 29 patients also analyzed for HSA functional changes. RESULTS: There was a significant decrease in the amounts of reduced HSA in conjunction with liver disease progression. Receiver operating characteristic curve analysis demonstrated that the levels of reduced HSA had high accuracy in determining disease progression. Functional alterations were strongly correlated to the levels of reduced HSA. BCAA supplementation led to substantial increases in the amount of reduced HSA. The altered HSA was able to scavenge significantly more radicals and restore the binding ability. CONCLUSION: This study describes structural alterations and functional disturbances of HSA in patients with chronic liver disease, and indicates that the levels of reduced HSA might reflect disease progression and the functional properties of HSA. Moreover, oral BCAA supplementation increases the amount of reduced HSA, thereby leading to the restoration of HSA function in cirrhotic patients.

Evaluation of sorafenib treatment and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a comparative study using the propensity score matching method.

While sorafenib (SFN) is the established worldwide standard therapeutic agent for advanced hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) is also considered a favorable treatment for some advanced HCCs. This study aimed to evaluate each treatment and provide an optimal therapeutic choice for advanced HCCs. We analyzed 72 patients treated with SFN and 128 patients receiving HAIC. Both treatment groups were analyzed for prognostic and disease progression factors, and matched pair analysis was performed using the propensity score matching method. The preferable status of intrahepatic lesions, that is, no lesions or only a single (< 3 cm) intrahepetic lesion, was positively associated with good prognosis and negatively associated with disease progression in the SFN group. Maximum tumor size (> 5 cm) and low albumin (≤ 3.4 g/dL) were poor prognostic and disease progression factors in the HAIC group. Analysis of 53 patients selected from each of the SFN and HAIC groups based on the propensity score matching method showed no significant differences in survival or disease progression between the two matched subgroups. On the other hand, progression-free survival (PFS) in the HAIC-matched subgroup was significantly longer than in the SFN-matched subgroup, particularly in patients with portal vein invasion (PVI) and/or without extrahepatic spread (EHS). The treatment efficacy of HAIC is similar to that of SFN regarding survival and disease progression. Longer PFS might be expected for HAIC compared with SFN, particularly in patients with PVI and/or without EHS.

Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases.

The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment.

Transcatheter arterial infusion chemotherapy with cisplatin-lipiodol suspension in patients with hepatocellular carcinoma.

PURPOSE: The aim of this study was to investigate the antitumor efficacy of treatment, identify prognostic factors, and construct a prognostic index in patients with hepatocellular carcinoma treated by transcatheter arterial infusion chemotherapy (TAI) using cisplatin suspended in lipiodol. METHODS: We analyzed the outcomes in a total of 94 consecutive patients with previously untreated hepatocellular carcinoma who were treated by TAI using cisplatin suspended in lipiodol. RESULTS: Twenty-seven patients (29%) showed complete response and 21 patients (22%) showed partial response, with an overall response rate of 51% (95% confidence interval, 41-61%). The median survival time was 2.5 years and the proportions of survivors at 1, 2, and 5 years were 81.6, 65.2, and 18.3%, respectively. The results of multivariate analysis indicated a significant association of serum albumin > or =3.0 g/dL, maximum tumor size < or =3.0 cm, absence of ascites, and unilateral distribution of the tumors with a favorable survival. For clinical application, we also propose a prognostic index based on a combination of these prognostic factors. Based on this index, the patients were classified into three groups: those with good, intermediate, and poor prognosis. The median survival times in these three groups were 4.3, 2.7, and 1.1 years, respectively (p < 0.01). CONCLUSIONS: TAI with cisplatin suspended in lipiodol exhibited favorable tumor efficacy and survival in patients with hepatocellular carcinoma. The prognostic factors identified and the index proposed based on these factors may be useful for predicting life expectancy, determining treatment strategies, and designing future clinical trials.

Transcatheter arterial chemotherapy with and without embolization in patients with hepatocellular carcinoma.

OBJECTIVE: This study compared the antitumor effect, adverse effects and survival between transcatheter arterial embolization (TAE) and transcatheter arterial infusion chemotherapy (TAI) in patients with hepatocellular carcinoma (HCC). METHODS: The study population consisted of 168 consecutive patients with advanced HCC treated with transcatheter arterial treatments using cisplatin suspended in lipiodol. Among these, 74 patients were treated with TAE, and the remaining 94 patients were treated with TAI. RESULTS: There were no significant differences in any baseline characteristics except hemoglobin, platelets, albumin, and glutamic pyruvic transaminase. Complete or partial tumor response was achieved in 54 patients (73%) in the TAE group and in 48 patients (51%) in the TAI group (p < 0.01). There were two treatment-related deaths caused by acute hepatic failure and acute renal failure in the TAE group. Nausea and deterioration of serum transaminase after TAE were significantly more severe than after TAI. Median survival time and survival rates at 5 years were 3.1 years and 25% in the TAE group, and 2.5 years and 18% in the TAI group (p = 0.37). CONCLUSION: TAE has a higher antitumor effect than TAI, but does not significantly improve the survival of patients with HCC.

Long-term follow-up of hepatic arterial chemoembolization with cisplatin suspended in iodized oil for hepatocellular carcinoma.

BACKGROUND/AIMS: We developed a method to suspend cisplatin in lipiodol (lipiodol-cisplatin suspension) for treating hapatocellular carcinoma. We evaluated the results of the long-term follow-up of lipiodol-cisplatin suspension therapy and the augmentation of its anti-cancer effect when in combination with transcatheter arterial embolization. METHODOLOGY: Hepatic arterial injection chemotherapy with lipiodol-cisplatin suspension was performed in 239 patients with hepatocellular carcinoma without distant metastases. One hundred and forty-three patients treated with lipiodol-cisplatin suspension alone were clinically compared to 96 patients treated with lipiodol-cisplatin suspension and transcatheter arterial embolization. RESULTS: Complete and partial responses were obtained in 83 cases (53.2%) in the lipiodol-cisplatin suspension alone group compared to 60 cases (62.5%) in the lipiodol-cisplatin suspension and transcatheter arterial embolization group. The survival rate of the former was 29.6% at 5 years, and of the latter was 24.2% at 5 years. The difference in survival rates between the two groups was not significant, however, in both groups excellent anti-cancer effects and prolongation of survival were seen compared to previous transcatheter arterial embolization methods. CONCLUSIONS: Lipiodol-cisplatin suspension therapy has an excellent anti-cancer effect superior to previous transcatheter arterial embolization methods and prolongs the survival rate for the patients with hapatocellular carcinoma.