Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma.

OBJECTIVE: The efficacy and safety of hepatic resection (HR) to treat patients with Barcelona Clinic Liver Cancer (BCLC) stage B and C hepatocellular carcinoma (HCC) was retrospectively assessed. BACKGROUND: Although guidelines from the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease do not recommend HR for treating BCLC stage B/C HCC, several Asian and European studies have come to the opposite conclusions. METHODS: A consecutive sample of 1259 patients with BCLC stage B/C HCC who underwent HR (n = 908) or transarterial chemoembolization (TACE, n = 351) were included. Moreover, propensity score-matched patients were analyzed to adjust for any baseline differences. In parallel with this retrospective clinical study, the MEDLINE database was searched for studies evaluating the efficacy and safety of HR for BCLC stage B/C HCC. RESULTS: Among our patient sample, the 90-day mortality rate in the HR group was 3.1%. HR provided a survival benefit over TACE at 1, 3, and 5 years (88% vs 81%, 62% vs 33%, and 39% vs 16%, respectively; all P < 0.001). Propensity scoring and subgroup analyses based on tumor size, tumor number, presence or absence of macrovascular invasion, and portal hypertension (PHT) also showed that HR was associated with better long-term survival than TACE. All 36 studies identified in our literature search reported that HR is associated with good long-term survival and low morbidity. Multivariate analyses revealed that alpha-fetoprotein more than or equal to 400 ng/mL, diabetes mellitus, macrovascular invasion, and PHT are independent predictors of poor prognosis in patients with BCLC stage B/C HCC. CONCLUSIONS: Our clinical and literature analyses suggest that in patients with HCC with preserved liver function, the presence of large, solitary tumors, multinodular tumors, macrovascular invasion, or PHT are not contraindications for HR.

Postoperative use of the chemopreventive vitamin K2 analog in patients with hepatocellular carcinoma.

AIM: To evaluate the chemopreventive efficacy of vitamin K2 (VK2) analog in patients with hepatocellular carcinoma (HCC) after curative hepatic resection or local ablation, since a recent randomized control trial (RCT) and systematic review have given contradictory results. METHODS: MEDLINE, EMBASE and Cochrane library databases were systematically searched through the end of May 2012. Meta-analysis of RCTs and cohort studies was performed to estimate the effects of the VK2 analog on tumor recurrence rate and overall survival (OS). Risk ratios (RRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Six RCTs and one cohort study involving a total of 930 patients were included. VK2 analog therapy did not reduce the 1-year recurrence rate, with a pooled RR of 0.67 (95% CI 0.39-1.13, p = 0.13). However, VK2 analog therapy was associated with a significant reduction in the 2- and 3-year tumor recurrence rates, with respective pooled RRs of 0.65 (95% CI 0.51-0.83, p<0.001) and 0.70 (95% CI = 0.58-0.85, p<0.001). The therapy was also associated with a significant improvement in 1-, 2-, and 3-year OS, with respective pooled RRs of 1.03 (95% CI 1.01-1.05, p = 0.02), 1.11 (95% CI 1.03-1.19, p = 0.005) and 1.14 (95% CI 1.02-1.28, p = 0.02). None of the studies reported adverse effects attributable to VK2 analog therapy. CONCLUSION: The VK2 analog may reduce recurrence rate after 1 year and improve OS in HCC patients as early as 1 year. However, these findings should be considered preliminary since the majority of patients came from an RCT with survival data out to only 1 year. More extensive studies with larger sample sizes and longer follow-up are needed.

Meta-analysis of microsomal epoxide hydrolase gene polymorphism and risk of hepatocellular carcinoma.

BACKGROUND: Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in microsomal epoxide hydrolase (mEH). Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent. METHODS: PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Eleven studies were included in the meta-analysis, involving 1,696 HCC cases and 3,600 controls. The 113His- mEH allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.35, 95% CI = 1.04-1.75, p = 0.02), homozygote comparison (OR = 1.65, 95% CI = 1.07-2.54, p = 0.02) and a recessive genetic model (OR = 1.54, 95% CI = 1.21-1.96, p<0.001), while individuals carrying the Arg139Arg mEH genotype had no association with increased or decreased risk of HCC. CONCLUSION: The 113His- allele polymorphism in mEH may be a risk factor for hepatocarcinogenesis, while the mEH 139Arg- allele may not be a risk or protective factor. There is substantial evidence that mEH polymorphisms interact synergistically with other genes and the environment to modulate risk of HCC. Further large and well-designed studies are needed to confirm these conclusions.