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Background and Aim: Several factors, including proangiogenic cytokines, have been reported as predictive markers for the treatment effect of sorafenib in patients with hepatocellular carcinoma (HCC); however, most of them were determined based on one‐time measurements before treatment. Methods: We consecutively recruited 80 advanced HCC patients who were treated with sorafenib prospectively. Serum levels of eight proangiogenic cytokines and the appearance of adverse events were monitored periodically, and their correlations with the prognoses of the patients were evaluated. Results: Among six significant risk factors for overall survival in univariate analyses, high angiopoietin‐2 (hazard ratio, 2.06), high hepatocyte growth factor (hazard ratio, 2.08), and poor performance status before the treatment (hazard ratio, 2.48) were determined as independent risk factors. In addition, high angiopoietin‐2 at the time of progressive disease was a marker of short post‐progression survival (hazard ratio, 4.27). However, there was no significant variable that predicted short progression‐free survival except the presence of hepatitis B virus surface antigen. Conclusions: Predictions of overall survival and post‐progression survival were possible by periodically measuring serum proangiogenic cytokines, especially angiopoietin‐2, in patients with HCC treated with sorafenib. [ABSTRACT FROM AUTHOR]

Aim Most of the modification of N-glycosylation reported in cancers including hepatocellular carcinoma ( HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N-glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application. Methods We analyzed sera from 105 patients with chronic hepatitis/liver cirrhosis ( CH/ LC) and age-/sex-matched healthy volunteers ( HLT), as well as from 114 patients with HCC. Serum N-glycan profiles were measured comprehensively by a new, quantitative, high-throughput method and compared with clinical parameters. Results The total amount of N-glycan expression was significantly higher in patients with CH/ LC than in HLT; however, no differences were observed between CH/ LC and HCC patients. In HCC patients, multi-antennary glycans with fucose residues, particularly m/z 3195, were increased compared with CH/ LC patients. The expression of m/z 3195 was high, especially in patients with a high number of intrahepatic lesions (>3), large tumor size (>3 cm), macroscopic vascular invasion or metastasis. The ratio of pairs of glycans on the same path of the biosynthesis pathway ( m/z 3195/1914) showed a higher area under the receiver-operator curve of 0.810 than any other single glycan to distinguish HCC from CH/ LC. Conclusion We demonstrate the full spectrum of the alterations of serum N-glycans comprehensively in patients with liver disease, and elucidate the possible use of glycans as novel biomarkers of liver disease progression. [ABSTRACT FROM AUTHOR]

Aim Recently, a relationship between platelets and cancer metastasis has been reported. The aim of this study is to elucidate the risk factors for extrahepatic metastasis ( EHM), with emphasis on association with platelets in patients, with hepatocellular carcinoma ( HCC). Methods We examined risk factors for EHM in 1613 consecutive, newly diagnosed HCC patients by logistic regression analysis (case-control study). We also examined the factors by Cox proportional hazard model in a retrospective cohort fashion in 803 patients who received non-curative treatment for HCC. Results In the case-control study, multivariate analysis revealed that high platelet counts (odds ratio [ OR] = 4.84; 95% confidence interval [ CI] = 1.29-29.54; P = 0.01), high tumor number and the presence of macroscopic vascular invasion were significantly associated with EHM. In the cohort study, EHM was diagnosed in 71 patients during the study period (mean observation time = 23.3 months). On multivariate analysis, high tumor number, high des-γ-carboxyprothrombin ( DCP) and Child- Pugh class A were significantly correlated with EHM, and the patients with high platelet counts tended to develop EHM ( OR = 1.73; 95% CI = 0.99-3.14; P = 0.055). Conclusion HCC patients with high platelet counts, as well as large numbers of tumors, high serum DCP and Child- Pugh class A, are at risk for EHM. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation ( RFA) is frequently used to treat early stage hepatocellular carcinoma. Two of the most cumbersome side-effects of the ablation procedure are intractable pain and vagotonia when deep sedation is not used. We describe local injection of anesthetic into Glisson's sheath as a new technique for overcoming these problems. Lidocaine was injected into Glisson's sheath when radiofrequency ablation of hepatocellular carcinomas, which were located adjacent to Glisson's sheath, could not be continued due to severe pain ( n = 8) or bradycardia ( n = 3). In all three patients who showed vagotonia with bradycardia during the ablations, injection of lidocaine prevented bradycardia, allowing completion of the radiofrequency ablation. Pain was reduced in all eight patients who experienced pain during ablation. No side-effects were observed during the procedures. Injection of anesthetic into Glisson's sheath is simple and effective for reducing intractable pain and vagotonia associated with RFA. [ABSTRACT FROM AUTHOR]

Aim We investigated whether continuous sorafenib administration keeps suppressing the growth of hepatocellular carcinoma ( HCC) after first progressive disease ( PD), and whether it prolongs patients' survival. Methods The size of metastatic lesions was measured in 36 patients with advanced HCC treated with sorafenib. The tumor growth rates before and after radiological PD as well as survival were compared between the patients who continued ( n = 23) and stopped ( n = 13) sorafenib at first radiological PD. Results The growth rate did not differ between before and after PD in patients who continued sorafenib, while it increased after PD in patients who stopped sorafenib at PD ( P = 0.002). Survival beyond first progression was longer in patients who continued sorafenib than in those who stopped it at PD ( P = 0.012), and this tendency was observed even when the analysis was limited to Child- Pugh class A patients ( P = 0.085). Conclusion Sorafenib administration beyond first radiological PD could continuously suppress HCC growth and may have survival benefit. [ABSTRACT FROM AUTHOR]

Aim Des-γ-carboxyprothrombin ( DCP) is known to be increased by the use of sorafenib for the treatment of hepatocellular carcinoma ( HCC), despite its therapeutic efficacy. In addition to the tumor progression, hypoxia that impairs vitamin K uptake is known to induce DCP and this mechanism may explain DCP elevation by sorafenib. In this study, we tried to evaluate the effect of sorafenib treatment using a new marker, NX-DCP, which is specific to vitamin K absence. Methods Serum DCP and NX-DCP were measured in 50 consecutive HCC patients before and 1 week after starting sorafenib, and compared with the treatment effect using the modified Response Evaluation Criteria in Solid Tumors guidelines. Results DCP and NX-DCP increased 1.58- (median, range 0.21-28.7) and 1.20-fold (median, range 0.41-14.2) after the administration of sorafenib, respectively. The increases of both markers were less than twofold in approximately half of the patients (low-elevation group). However, 12 patients showed over twofold increase of both DCP and NX-DCP (double-elevation group), and eight patients showed over twofold increase of DCP alone ( DCP-elevation group). The disease control rate ( DCR) of the DCP-elevation group (12.5%) was significantly lower than those of the double-elevation group (75.0%, P = 0.020) and the low-elevation group (60.0%, P = 0.042). Progression-free survival ( PFS) was significantly shorter in the DCP-elevation group than in the double-elevation group ( P = 0.006) and the low-elevation group ( P = 0.001). Conclusion NX-DCP in combination with DCP could be a useful biomarker of sorafenib treatment for advanced HCC. [ABSTRACT FROM AUTHOR]