Addition of local hepatic therapy to sorafenib in patients with advanced hepatocellular carcinoma (stage BCLC C).

BACKGROUND/AIMS: For most patients with hepatocellular carcinoma (HCC), diagnosis is invariably done only in the advanced stages of the disease. For advanced, non-metastatic stage, standard therapy is transarterial chemoembolization (TACE). For metastatic disease, the recommended therapy is systemic treatment with sorafenib. In this study, we evaluated the benefit of an additional local hepatic treatment for patients with advanced metastatic disease. METHODS: In a retrospective study, we assessed the overall survival (OS), time to progression (TTP), and disease control rate (DCR) in 37 patients with metastasized HCC treated with sorafenib. Sixteen patients received additional local therapy, while 21 patients received only sorafenib. RESULTS: Median OS of patients with combined therapy was significantly higher with 25 months (95% CI: 13.7-36.3 months) as compared to 11 months (95% CI: 6.2-15.8 months) in patients treated with sorafenib alone. TTP was 7 months (95% CI: 5.3-8.7 months) compared to 5 months (95% CI: 3-7 months) and DCR was 87 versus 72% after 3 months and 31 versus 22% after 9 months. CONCLUSION: These data suggest that control of the liver tumor burden by local therapy in combination with sorafenib might prove beneficial for metastasized HCC. Randomised studies are needed to confirm this exploratory finding.

Prognosis of patients with hepatocellular carcinoma. Validation and ranking of established staging-systems in a large western HCC-cohort.

BACKGROUND: HCC is diagnosed in approximately half a million people per year, worldwide. Staging is a more complex issue than in most other cancer entities and, mainly due to unique geographic characteristics of the disease, no universally accepted staging system exists to date. Focusing on survival rates we analyzed demographic, etiological, clinical, laboratory and tumor characteristics of HCC-patients in our institution and applied the common staging systems. Furthermore we aimed at identifying the most suitable of the current staging systems for predicting survival. METHODOLOGY/PRINCIPAL FINDINGS: Overall, 405 patients with HCC were identified from an electronic medical record database. The following seven staging systems were applied and ranked according to their ability to predict survival by using the Akaike information criterion (AIC) and the concordance-index (c-index): BCLC, CLIP, GETCH, JIS, Okuda, TNM and Child-Pugh. Separately, every single variable of each staging system was tested for prognostic meaning in uni- and multivariate analysis. Alcoholic cirrhosis (44.4%) was the leading etiological factor followed by viral hepatitis C (18.8%). Median survival was 18.1 months (95%-CI: 15.2-22.2). Ascites, bilirubin, alkaline phosphatase, AFP, number of tumor nodes and the BCLC tumor extension remained independent prognostic factors in multivariate analysis. Overall, all of the tested staging systems showed a reasonable discriminatory ability. CLIP (closely followed by JIS) was the top-ranked score in terms of prognostic capability with the best values of the AIC and c-index (AIC 2286, c-index 0.71), surpassing other established staging systems like BCLC (AIC 2343, c-index 0.66). The unidimensional scores TNM (AIC 2342, c-index 0.64) and Child-Pugh (AIC 2369, c-index 0.63) performed in an inferior fashion. CONCLUSIONS/SIGNIFICANCE: Compared with six other staging systems, the CLIP-score was identified as the most suitable staging system for predicting prognosis in a large German cohort of predominantly non-surgical HCC-patients.

Relation of gallbladder motility to viscosity and composition of gallbladder bile in patients with cholesterol gallstones.

BACKGROUND/AIMS: Increased viscosity and supersaturation of cholesterol in gallbladder bile, as well as an impaired motility of the gallbladder, are considered to be important factors in the pathogenesis of cholesterol gallstones. However, the relation of these parameters has not yet been determined. MATERIAL AND METHODS: Bile viscosity (mPa s) was measured by rotation viscosimetry and the composition of gallbladder bile was determined using standard methodology. Gallbladder motility was calculated as ejection fraction in percent of total volume 45 min after a test meal using ultrasonography in patients with gallstones prior to elective cholecystectomy. RESULTS: The study included 35 patients with cholesterol gallstones. Viscosity of gallbladder bile ranged between 0.9 and 12.5 mPa s (median 2.2 mPa s) and an ejection fraction of the gallbladder of 55.4 +/- 18.3% (mean +/- SD) was determined. No significant correlation (r = 0.19, p < 0.2) between the 2 parameters could be calculated. Analysis of the composition of gallbladder bile revealed a positive correlation of all components to biliary viscosity but not to the motility of the gallbladder, with the exceptions of a negative correlation (r = 0.39, p < 0.02) between mucin concentration and the ejection fraction at 45 min after the test meal. CONCLUSIONS: The motility of the gallbladder appears to be unrelated to the viscosity of gallbladder bile or gallbladder bile composition. The negative correlation between the ejection fraction of the gallbladder and mucin concentration of gallbladder bile suggests that chronic inflammation of the gallbladder wall is associated with both an impaired motility of the gallbladder and increased mucin release into gallbladder bile.

Chemoembolization combined with pravastatin improves survival in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown to inhibit growth and to induce apoptosis in human hepatocellular carcinoma (HCC) cells. However, the potential benefit of pravastatin in HCC patients has still not been characterized, which prompted us to test the efficacy of pravastatin in patients with advanced HCC. METHODS: We investigated prospectively a cohort of 183 HCC patients who had been selected for palliative treatment by transarterial chemoembolization (TACE). Fifty-two patients received TACE combined with pravastatin (20-40 mg/day) and 131 patients received chemoembolization alone. Six independent predictors of survival according to the Vienna survival model for HCC were equally distributed in both groups. RESULTS: During the observation period of up to 5 years, 31 (23.7%) out of 131 patients treated by TACE alone and 19 (36.5%) out of 52 patients treated by TACE and pravastatin survived. Median survival was significantly longer in HCC patients treated by TACE and pravastatin (20.9 months, 95% CI 15.5-26.3, p = 0.003) than in HCC patients treated by TACE alone (12.0 months, 95% CI 10.3-13.7). CONCLUSION: Combined treatment of chemoembolization and pravastatin improves survival of patients with advanced HCC in comparison to patients receiving chemoembolization alone.

Liver resection or combined chemoembolization and radiofrequency ablation improve survival in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: To evaluate the long-term outcome of surgical and non-surgical local treatments of patients with hepatocellular carcinoma (HCC). METHODS: We stratified a cohort of 278 HCC patients using six independent predictors of survival according to the Vienna survival model for HCC (VISUM-HCC). RESULTS: Prior to therapy, 224 HCC patients presented with VISUM stage 1 (median survival 18 months) while 29 patients were classified as VISUM stage 2 (median survival 4 months) and 25 patients as VISUM stage 3 (median survival 3 months). A highly significant (p < 0.001) improved survival time was observed in VISUM stage 1 patients treated with liver resection (n = 52; median survival 37 months) or chemoembolization (TACE) and subsequent radiofrequency ablation (RFA) (n = 44; median survival 45 months) as compared to patients receiving chemoembolization alone (n = 107; median survival 13 months) or patients treated by tamoxifen only (n = 21; median survival 6 months). Chemoembolization alone significantly (p < or = 0.004) improved survival time in VISUM stage 1-2 patients but not (p = 0.341) in VISUM stage 3 patients in comparison to those treated by tamoxifen. CONCLUSION: Both liver resection or combined chemoembolization and RFA improve markedly the survival of patients with HCC.