Hepatocellular carcinoma cases with high levels of c-Raf-1 expression may benefit from postoperative adjuvant sorafenib after hepatic resection even with high risk of recurrence.

BACKGROUND AND AIMS: Liver resection combined with postoperative sorafenib to prevent recurrence remains a controversial approach for cases of hepatocellular carcinoma (HCC), especially cases with a high risk of recurrence. This study aimed to investigate the efficacy and safety of liver resection combined with sorafenib for HCC with a high risk of recurrence. RESULTS: Most of the cases of HCC were caused by hepatitis B virus (HBV) infection (23 cases, 92%). Most of these tumors (21 cases, 84%) were stage III according to the TNM staging system (12 cases with IIIa, 9 cases with IIIb). In the months after hepatic resection, 19 of the 25 cases (76%) were diagnosed with HCC recurrence or metastasis. Based on the tumor histological biomarker grading system, the group with higher expression levels of c-Raf-1 showed significantly longer overall survival than the group with lower expression of c-Raf-1 (P = 0.012). However, the long-term tumor-free survival advantage disappeared (P = 0.061). Univariate and multivariate analyses indicated that higher expression of c-Raf-1 was significantly associated with better overall survival (hazard ratio [HR]: 1.842; 95% confidence interval [CI]: 1.211-2.542; P = 0.031) and tumor-free survival (HR: 1.319; 95% CI: 1.017-1.543; P = 0.046) in HCC patients who underwent radical hepatic resection. PATIENTS AND METHODS: We retrospectively collected 25 HCC cases with a high risk of recurrence who underwent radical liver resection and who took sorafenib postoperatively from Jan 2010 to Dec 2012. Factors that might contribute to tumor recurrence and treatment failure such as clinical factors, tumor features, and molecular biomarkers were included in our analysis. CONCLUSIONS: HCC patients with a high risk of post-hepatic resection recurrence may benefit from postoperative sorafenib administered as an adjuvant therapy, especially in cases with high levels of c-Raf-1 expression on histological examination.

Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study.

PURPOSE: Brivanib is a dual inhibitor of vascular-endothelial growth factor and fibroblast growth factor receptors that are implicated in the pathogenesis of hepatocellular carcinoma (HCC). Our multinational, randomized, double-blind, phase III trial compared brivanib with sorafenib as first-line treatment for HCC. PATIENTS AND METHODS: Advanced HCC patients who had no prior systemic therapy were randomly assigned (ratio, 1:1) to receive sorafenib 400 mg twice daily orally (n = 578) or brivanib 800 mg once daily orally (n = 577). Primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), and safety. RESULTS: The primary end point of OS noninferiority for brivanib versus sorafenib in the per-protocol population (n = 1,150) was not met (hazard ratio [HR], 1.06; 95.8% CI, 0.93 to 1.22), based on the prespecified margin (upper CI limit for HR ≤ 1.08). Median OS was 9.9 months for sorafenib and 9.5 months for brivanib. TTP, ORR, and DCR were similar between the study arms. Most frequent grade 3/4 adverse events for sorafenib and brivanib were hyponatremia (9% and 23%, respectively), AST elevation (17% and 14%), fatigue (7% and 15%), hand-foot-skin reaction (15% and 2%), and hypertension (5% and 13%). Discontinuation as a result of adverse events was 33% for sorafenib and 43% for brivanib; rates for dose reduction were 50% and 49%, respectively. CONCLUSION: Our study did not meet its primary end point of OS noninferiority for brivanib versus sorafenib. However, both agents had similar antitumor activity, based on secondary efficacy end points. Brivanib had an acceptable safety profile, but was less well-tolerated than sorafenib.

Health-related quality of life in living liver donors after transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) has recently emerged as an effective therapeutic alternative for patients with end-stage liver disease. In the meantime, the health-related quality of life (HRQoL) of the donors is becoming better appreciated. Here we aimed to review the current literature and summarize the effects of liver donation on the long-term HRQoL of living donors. DATA SOURCES: A literature search of PubMed using "donors", "living donor liver transplantation", "health-related quality of life", and "donation" was performed, and all the information was collected. RESULTS: The varied postoperative outcomes of liver donors are attributive to the different evaluation instruments used. On the whole, donors experienced good long-term physical and mental well-being with a few complaining of compromised quality of life due to mild symptoms or psychiatric problems. The psychosocial dimension has received increasing attention with the vocational, interpersonal and financial impact of liver donation on donors mostly studied. CONCLUSIONS: Generally, donors have a good HRQoL after LDLT. Nevertheless, to achieve an ideal donor outcome, further work is necessary to minimize the negative effects as well as to incorporate recent progress in regenerative medicine.

[Modified total hepatic vascular exclusion for liver extracapsular resection of giant hepatic cavernous hemangioma].

OBJECTIVE: To explore the feasibility of intraoperative autologous transfusion in modified total hepatic vascular exclusion under normal temperature for extracapsular resection of giant hepatic hemangioma. METHODS: The clinical data of 32 patients undergoing hepatic resection with total hepatic vascular exclusion requiring intraoperative autologous transfusion were analyzed retrospectively. The tumors in these cases involved the proximal hepatic veins and inferior vena cava, with hemangioma volume ranging from 12 cm x 15 cm to 18 cm x 40 cm. RESULTS: The hemangioma were completely resected in all patients, who all recovered smoothly. In one case, hemangioma rupture occurred during dissociation of the liver, resulting in massive hemorrhage which required blood transfusion of 6000 ml. Four patients received blood transfusion of 400-800 ml, and the other 27 had no blood transfusion. Only 8 patients underwent pringle maneuver with resection, whereas the other 27 underwent total hepatic vascular exclusion during liver resection for 5-30 min (mean 16 min). CONCLUSION: Intraoperative autologous transfusion in modified total hepatic vascular exclusion under normal temperature is feasible and safe for extracapsular resection of huge hepatic hemangioma adjacent to the major arteries.

Autologous transfusion with modified total hepatic vascular exclusion for extracapsular resection of giant hepatic cavernous hemangioma.

BACKGROUND: This paper was to review the effects of intraoperative autologous transfusion during modified, normal-temperature, total hepatic vascular exclusion (THVE) for extracapsular resection of giant hepatic cavernous hemangioma. METHODS: The clinical data from 28 patients, who underwent hepatic resection requiring intraoperative autologous transfusion with the cell-saver apparatus, were analyzed retrospectively. The tumors in the 28 patients involved the proximal hepatic veins and inferior vena cava. The volume of these hemangiomas ranged from 12 x 15 cm to 18 x 40 cm. All patients had varying degrees of THVE. RESULTS: The 28 patients with hemangioma received integrated resection and recovered. One patient had rupture of tumors resulting in massive hemorrhage of 6000 ml during liver resection; 4 patients had blood transfusions of 400-800 ml; the other 23 patients had no blood transfusion. Only 6 patients underwent the Pringle maneuver with resection. The other 22 patients underwent THVE during the liver resection. The interval of THVE was 5-30 minutes (mean 16 minutes). CONCLUSIONS: Intraoperative autologous transfusion during modified, normal-temperature THVE for extracapsular resection of huge hepatic cavemous hemangioma is feasible.

[Clinical study on the treatment of severe acute pancreatitis by integrated traditional Chinese medicine and Western medicine].

OBJECTIVE: To sum up clinical experiences and formulate a new treatment program for the effective managment of severe acute pancreatitis(SAP) by integrated TCM and western medicine. METHODS: The therapeutic regimens and end results of 1376 cases of SAP in three periods were reviewed and analyzed. Period I (1980-1990) was characterized by early surgical intervention supplemented with integrated traditional Chinese and western medical therapy, period II (1991-1993) by integrated traditional Chinese and western medical therapy supplemented with surgery for early complications, and period III (1994-2003) by integrated traditional Chinese and western medical therapy supplemented with surgery for local infectious complications at a late stage in the course of disease. RESULTS: With use of integrated traditional Chinese and western medical therapy in the treatment of SAP, the proportion of surgical operation and the case-fatality rate kept declining in the three consecutive periods, the proportions of operation being 77.59%, 54.54% and 19.38%, and the case-fatality rates being 40.52%, 17.17% and 10.77%, respectively. CONCLUSION: Integrated TCM and western medicine is effective for most SAP cases, and surgery is indicated mainly for late complications such as necrotizing infection. Early surgery should be handled with more circumspection and strictness in most of the patients with SAP.