Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES: We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS: Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS: HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.

Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3 cm: a randomized controlled trial.

CONTEXT: Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) therapy has been used for patients with large hepatocellular carcinoma tumors, but the survival benefits of combined treatment are not known. OBJECTIVE: To compare rates of survival of patients with large hepatocellular carcinoma tumors who received treatment with TACE combined with RFA therapy (TACE-RFA), TACE alone, and RFA alone. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial conducted from January 2001 to May 2004 among 291 consecutive patients with hepatocellular carcinoma larger than 3 cm at a single center in China. INTERVENTION: Patients were randomly assigned to treatment with combined TACE-RFA (n = 96), TACE alone (n = 95), or RFA alone (n = 100). MAIN OUTCOME MEASURES: The primary end point was survival and the secondary end point was objective response rate. RESULTS: During a median 28.5 months of follow-up, median survival times were 24 months in the TACE group (3.4 courses), 22 months in the RFA group (3.6 courses), and 37 months in the TACE-RFA group (4.4 courses). Patients treated with TACE-RFA had better overall survival than those treated with TACE alone (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.33-2.63; P < .001) or RFA (HR, 1.88; 95% CI, 1.34-2.65; P < .001). In a preplanned substratification analysis, survival was also better in the TACE-RFA group than in the RFA group for patients with uninodular hepatocellular carcinoma (HR, 2.50; 95% CI, 1.42-4.42; P = .001) and in the TACE-RFA group than the TACE group for patients with multinodular hepatocellular carcinoma (HR, 1.99; 95% CI, 1.31-3.00; P < .001). The rate of objective response sustained for at least 6 months was higher in the TACE-RFA group (54%) than with either TACE (35%; rate difference, 0.19; 95% CI, 0.06-0.33; P = .009) or RFA (36%; rate difference, 0.18; 95% CI, 0.05-0.32; P = .01) treatment alone. CONCLUSION: In this patient group, TACE-RFA was superior to TACE alone or RFA alone in improving survival for patients with hepatocellular carcinoma larger than 3 cm. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00479050.

Ethyl pyruvate improves survival and ameliorates distant organ injury in rats with severe acute pancreatitis.

OBJECTIVE: To evaluate the effect of ethyl pyruvate (EP) in improving the survival and ameliorating distant organ damage and to investigate the role of high-mobility group box (HMGB) 1 in rats with established severe acute pancreatitis (SAP). METHODS: Severe acute pancreatitis was induced by retrograde infusion of sodium taurodeoxycholate (5%, 1 mL/kg) into the biliopancreatic ducts in male Wistar rats. The rats were infused intravenously with EP of 40 mg/kg, 4 mg/kg, and 0.4 mg/kg initiating 12 hours, and EP of 40 mg/kg was administered beginning 2 hours before surgery (-2 hours) and 12, 24, and 36 hours after induction of SAP; then, the mortality was recorded. Serum tumor necrosis factor alpha, interleukin (IL) 6, and IL-1beta were measured using enzyme-linked immunosorbent assay. High-mobility group box 1 levels were measured using Western immunoblotting analysis. RESULTS: Serum HMGB1 levels were increased dramatically after 12 hours, remained at high levels for 72 hours, and were significantly higher in rats with SAP than in those with mild and moderate pancreatitis (P < 0.01). Treatment with EP (40 mg/kg) conferred protection from lethality of SAP (EP survival [63%] vs vehicle survival [6.3%]; P < 0.001). No survival advantage occurred when treatment was initiated 36 hours after surgery, but administration beginning 2 hours before operation (-2 hours) and 12 and 24 hours after induction of SAP significantly increased survival. Ethyl pyruvate treatment significantly decreased serum HMGB1, tumor necrosis factor alpha, IL-1beta, and IL-6 levels and ameliorated extrapancreatic organ dysfunction in rats with SAP. CONCLUSIONS: Ethyl pyruvate improves survival and ameliorates distant organ injury of SAP. These beneficial effects of EP are because of the modulation of HMGB1 and other inflammatory cytokine responses.