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Background: Abnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the potential of serum FGF19 as a novel tumor marker of HCC based on a sandwich enzyme-linked immunosorbent assay (ELISA).Methods: The serum FGF19 levels of 304 patients with HCC was measured by ELISA. The serum levels of existing markers, including alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were determined by chemiluminescence enzyme immunoassay. Both diagnostic value of FGF19 and its changes after curative ablation therapy was further examined.Results: The median FGF19 levels in controls, chronic liver disease patients, and primary HCC patients, were 78.8 pg/mL, 100.1 pg/mL, and 214.5 pg/mL, respectively. The subsequent receiver operating characteristic curves (ROC) successfully determined an optimal cut-off value of 200.0 pg/mL. The area under the ROC curve (AUC) of FGF19 for HCC detection was comparable to those of AFP and DCP. Of importance, FGF19 showed higher sensitivity for the detection of small HCC (solitary cancer with diameter < 20 mm) than those of existing markers. In addition, 43 out of 79 cases (54.4%) with normal AFP and DCP (so-called "double negative HCC") exhibited serum FGF19 level ≥ 200 pg/mL. In 45 HCC patients treated with curative ablation therapy, serum FGF19 levels changed from 257.4 pg/mL to 112.0 pg/mL after the treatment.Conclusion: Our findings reveal that FGF19 can be a potential novel biomarker for HCC. Although FGF19 is not necessarily a substitute for existing markers, it may help improve the prognosis in HCC patients owing to its resourceful use in various aspects of HCC management and treatment. [ABSTRACT FROM AUTHOR]

We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log‐rank test determined the significance of each prognostic factor. Elevated alpha‐fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19‐9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First‐line chemotherapy included platinum‐containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression‐free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child‐Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum‐containing regimens (HR: 15.83 [95% CI: 2.25‐111.43], P = .006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second‐line therapy. In conclusion, the platinum‐containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation (RFA) is commonly used to locally treat hepatocellular carcinoma (HCC). However, when tumors are close to the Glisson’s capsule, RFA may induce injury in this region, complicating therapeutic efforts. We investigated the impact of RFA-induced Glisson’s capsule-associated complications on liver function and prognosis of HCC patients. Methods: We retrospectively reviewed our patient database and found 170 early-stage HCC patients treated via RFA from April 2004 to December 2012. We defined RFA-induced Glisson’s capsule-associated complication as lasting hepatic arterioportal (AP) fistula, major intrahepatic bile-duct dilatation (affecting two or more subsegments), or hepatic infarction. We also defined liver failure as initial occurrence of either total bilirubin increase (>3.0 mg/dL), uncontrolled ascites, or encephalopathy. Results: In our cohort, 15 patients had RFA-induced Glisson’s capsule-associated complications (incidence of related complications, with some overlap: lasting AP fistula, n = 9; major intrahepatic bile-duct dilatation, n = 7; and hepatic infarction, n = 2). The cumulative incidence of liver failure before stage progression was significantly higher and the median overall survival (OS) was significantly lower (52.3 months) in HCC patients with Glisson’s capsule-associated complications than in those without Glisson’s capsule-associated complications (95.0 months). In addition, multivariate analysis demonstrated that Glisson’s capsule-associated complication was a significant independent factor associated with OS. Conclusions: In this study, we have shown that early-stage HCC patients with RFA-induced Glisson’s capsule-associated complications may have higher risks in poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Hypovascular nodules often occur together with hypervascular hepatocellular carcinoma (HCC). However, it remains controversial whether hypovascular nodules associated with hypervascular HCC have any prognostic value. This study evaluated the prognostic impact of hypovascular nodules co-existing with hypervascular HCC as diagnosed by computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), which can sensitively capture the dynamic changes in blood flow through the portal vein and hepatic artery in patients with early stage HCC. Methods: A total of 152 patients with hypervascular HCC (≤ 30 mm, ≤ 3 nodules), who underwent initial local ablation, were analyzed retrospectively. All patients received CTAP and CTHA prior to treatment. Overall survival (OS) was compared among group A (hypervascular HCC only, 107 patients) and group B (hypovascular nodules and hypervascular HCC, 45 patients). Results: Among all hypovascular nodules, 81% (46 of 57) developed hypervascularization within the follow-up period. The 1- and 2-year hypervascularization rates were 17% and 51%, respectively. OS was significantly longer for group A than for group B (P < 0.001). A Cox proportional-hazards model identified the presence of hypovascular nodules concurrent with hypervascular HCC as an independent poor prognostic factor. Conclusion: The prognosis of hypervascular HCC patients with hypovascular nodules detected during CTAP and CTHA is poor. Clinical HCC categories seem to be dissimilar between patients with and without hypovascular nodules. [ABSTRACT FROM AUTHOR]

Background: Treatment outcomes of sorafenib therapy may greatly vary depending not only on tumor spread but also on past clinical processes prior to sorafenib therapy and timing of sorafenib administration in the past clinical course of hepatocellular carcinoma (HCC). We evaluated the efficacy of sorafenib in patients with HCC, taking into account of their past clinical courses. Methods: Patients with HCC treated with sorafenib as a first-line systemic therapy, whose courses documented from the time of the initial diagnosis, were retrospectively analyzed. Results: Of the 123 patients receiving sorafenib therapy at an advanced-stage, baseline characteristics differed including the rate of hepatitis C virus, Child–Pugh class, and status of intrahepatic lesions according to stage progression processes. Overall survival (OS) in patients progressed directly from the early-stage (15.3 months) was significantly longer than that in patients diagnosed at the advanced-stage (5.3 months, P = 0.022) and progressed from the intermediate-stages (6.0 months, P = 0.041). Of 105 patients diagnosed at the intermediate-stage on past clinical courses, OS of starting sorafenib therapy before progression to the advanced-stage (67 patients) was significantly longer than for patients starting sorafenib therapy only after progression to the advanced-stage (38 patients) (P = 0.015). Conclusion: Characteristic differences between past stage progression processes might affect prognosis in advanced-stage HCC patients receiving sorafenib. Switching to sorafenib therapy before progression to the advanced-stage appears more effective than that after progression to the advanced-stage in patients diagnosed in the intermediate-stage on past clinical courses prior to sorafenib administration. [ABSTRACT FROM AUTHOR]

Background and Aim Whether an antiviral interferon ( IFN)-based therapy ( IBT) after curative treatment of hepatocellular carcinoma ( HCC) improves the prognosis in patients with hepatitis C virus ( HCV)-related HCC remains to be elucidated. Methods A total of 178 patients within the Milan criteria underwent curative treatment for HCV-related HCC. Both the time to beyond the Milan criteria ( TTBMC) and overall survival ( OS) were compared between the sustained virologic response ( SVR) ( IFN with SVR, n = 22), non- SVR ( IFN without SVR, n = 19), and non- IBT (control, n = 82) groups using propensity score matching analysis. Prognostic factors to predict survival were also determined by the Cox proportional-hazards model. Results TTBMC in the IFN with SVR group was significantly longer than those in the control and IFN without SVR groups ( P < 0.001 and P = 0.006, respectively), although no significant difference existed between the IFN without SVR and control groups. Similarly, OS of the IFN with SVR group was significantly longer than that of the control and IFN without SVR groups ( P < 0.001 and P = 0.029, respectively), although no significant difference existed between the IFN without SVR and control groups. The Cox proportional-hazards model identified SVR as an independent prognostic factor in these patients. The IFN with SVR group showed a 0.096-fold decrease in mortality risk compared with the control group (95% confidence intervals = 0.023-0.405; P = 0.001). Conclusion Elimination of HCV after curative treatment of patients with HCC within the Milan criteria inhibits recurrence and contributes to a preferential prognosis. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to elucidate the treatment efficacy and safety of gemcitabine monotherapy, and to identify prognostic factors in patients with advanced biliary tract cancer receiving this therapy. Method: The data of 100 patients with advanced biliary tract cancer who were treated with gemcitabine as first-line chemotherapy were reviewed retrospectively. Results: One patient showed complete response (1.0%) and 6 patients showed partial response (6.0%), yielding an overall response rate of 7.0%. The main grade 3/4 toxicities were neutropenia and leukopenia. The median survival, 1-year survival rate and progression-free survival were 7.3 months, 21.6% and 3.1 months, respectively. Multivariate analysis identified a performance status of 0-1, serum C-reactive protein level of <3.0 mg/dl, serum carcinoembryonic antigen level of <10 ng/ml and serum albumin level of ≥3.5 g/dl as factors independently associated with a favorable prognosis. Conclusions: Gemcitabine monotherapy showed modest efficacy with manageable toxicity in patients with biliary tract cancer. These results could be useful as reference data for optimizing treatment strategies and planning future clinical trials in patients with advanced biliary tract cancer. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]