Jian-Hong Zhong

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.

Comparison of Long-Term Survival of Patients with BCLC Stage B Hepatocellular Carcinoma after Liver Resection or Transarterial Chemoembolization

Background and Aims Treatment of patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma (BCLC-B HCC) is controversial. This study compared the long-term survival of patients with BCLC-B HCC who received liver resection (LR) or transarterial chemoembolization (TACE). Methods A total of 257 and 135 BCLC-B HCC patients undergoing LR and TACE, respectively, were retrospectively evaluated. Kaplan–Meier method was used for long-term survival analysis. Independent prognostic predictors were determined by the Cox proportional hazards model. Results The hospital mortality rate was similar between groups (3.1% vs. 3.7%; P = 0.76). However, the LR group showed a significantly higher postoperative complication rate than the TACE group (28 vs. 18.5%; P = 0.04). At the same time, the LR group showed significantly higher overall survival rates (1 year, 84 vs. 69%; 3 years, 59 vs. 29%; 5 years, 37 vs. 14%; P<0.001). Moreover, similar results were observed in the propensity score model. Three independent prognostic factors were associated with worse overall survival: serum AFP level (≥400 ng/ml), serum ALT level, and TACE. Conclusions LR appears to be as safe as TACE for patients with BCLC-B HCC, and it provides better long-term overall survival. However, prospective studies are needed to disclose if LR may be regarded as the preferred treatment for these patients as long as liver function is preserved.

Hepatic Resection as a Safe and Effective Treatment for Hepatocellular Carcinoma Involving a Single Large Tumor, Multiple Tumors, or Macrovascular Invasion

AbstractThis systematic review examined whether the available evidence justifies using hepatic resection (HR) during later stages of hepatocellular carcinoma (HCC), which contravenes treatment guidelines but is current practice at many medical centers.Official guidelines and retrospective studies recommend different roles for HR for patients with large/multinodular HCC or with HCC involving macrovascular invasion (MVI).Several databases were systematically searched for studies examining the safety and efficacy of HR for treating HCC involving a single large tumor (>5 cm) or multiple tumors, or for treating HCC involving MVI.We identified 50 studies involving 14 808 patients that investigated the use of HR to treat large/multinodular HCC, and 24 studies with 4389 patients that investigated HR to treat HCC with MVI. Median in-hospital mortality for patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non-Asian studies (7.3%, P < 0.001). Median overall survival (OS) was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients at both 1 year (81% vs 65%, P < 0.001) and 5 years (42% vs 32%, P < 0.001). Similar results were obtained for median disease-free survival at 1 year (61% vs 50%, P < 0.001) and 5 years (26% vs 24%, P < 0.001). However, median OS was similar for Asian and non-Asian patients with HCC involving MVI at 1 year (50% vs 52%, P = 0.45) and 5 years (18% vs 14%, P = 0.94). There was an upward trend in 5-year OS in patients with either type of HCC.HR is reasonably safe and effective at treating large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for HR in official treatment guidelines.

Postoperative adjuvant transarterial chemoembolization for participants with hepatocellular carcinoma : A meta-analysis

Aim:  The efficacy of transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC) is positive, but for postoperative HCC, many studies have reported controversial results. The present study aimed to evaluate the efficacy of postoperative adjuvant TACE for participants with HCC.

Adjuvant therapy options following curative treatment of hepatocellular carcinoma: A systematic review of randomized trials

AIMS Numerous postoperative therapies for preventing recurrence of hepatocellular carcinoma (HCC) have been reported, but their efficacy remains controversial and knowledge about adverse effects is limited. A systematic review of randomized controlled trials (RCTs) was performed to gain a comprehensive picture of the efficacy and risks of these therapies. METHODS MEDLINE, EMBASE and the Cochrane Library were systematically searched through July 2011. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS A total of 2989 patients from 28 RCTs involving 10 postoperative therapies were included. For interferon therapy, the estimated RR for the 2-year recurrence rate was 0.84 (95% CI 0.73-0.97, P = 0.02) and the overall survival (OS) was 1.15 (95% CI 1.07-1.22, P < 0.001). Postoperative therapy with the vitamin K2 analog did not lead to a significant reduction in the 1-year recurrence rate, with a pooled RR of 0.60 (95% CI 0.28-1.27, P = 0.18). However, it did slightly improve the 1-year OS, with a pooled RR of 1.03 (95% CI 1.00-1.05, P = 0.03). Transarterial chemotherapy with or without embolization, adoptive immunotherapy and heparanase inhibitor PI-88 therapy may delay tumor recurrence. The effects of acyclic retinoid, lipiodol-iodine-131 and tumor vaccine treatment were promising but require further study. All postoperative therapies except interferon administered intramuscularly were well tolerated by the majority of patients. CONCLUSIONS Use of adjuvant interferon is definitely associated with an increase in OS. Postoperative therapies involving acyclic retinoid, lipidol-iodine-131, or tumor vaccine may improve the OS of patients with HCC after curative treatment.

Albumin-bilirubin versus Child-Pugh score as a predictor of outcome after liver resection for hepatocellular carcinoma.

The Child–Pugh (CP) score is used widely to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin–bilirubin (ALBI) score has been validated as a predictor of overall survival in these patients. This study aimed to compare the ability of the ALBI and CP scores to predict outcomes in patients with HCC after liver resection with curative intent.

Postoperative therapy options for hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is associated with poor prognosis and often recurs even after curative hepatic resection (HR) or radiofrequency ablation (RFA). In fact, recurrence is the most frequent cause of postoperative death in patients with HCC; it can arise through intrahepatic metastasis by the primary tumor or through the emergence of de novo tumors. Even though studies have examined numerous adjuvant therapies and chemotherapies for their ability to prevent recurrence, no consensus recommendations exist about their clinical application. To gain a comprehensive picture of clinical options, we identified 39 randomized controlled trials, involving 4113 participants, which explore the efficacy of adjuvant or chemotherapies to prevent HCC recurrence after potentially curative HR or RFA. The available evidence suggests a significant improvement in recurrence-free survival and overall survival when transarterial chemoembolization is used for patients who are at high risk for recurrence, lamivudine for patients with hepatitis B virus (HBV)-related HCC (>500 copies of HBV DNA/ml), and interferon-α for patients with hepatitis C virus (HCV)-infected HCC. In contrast, available evidence does not definitively establish clinical benefits of interferon-β for patients with HCV-related HCC, interferon-α for patients with HBV-related HCC, or any of the following therapies for patients with HCC: iodine-125 brachytherapy, autologous tumor vaccination, adoptive immunotherapy, or therapy involving acyclic retinoid, vitamin K2 analog, iodine-131-labeled lipiodol, sorafenib, heparanase inhibitor PI-88, or capecitabine. Though the findings of our review should be interpreted with caution because of clinical heterogeneity and small sample size in the included trials, they highlight gaps in the evidence base, and therefore, may guide future research.

Epidermal growth factor gene polymorphism and risk of hepatocellular carcinoma: a meta-analysis.

Background Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in the epidermal growth factor (EGF) gene. Previous work suggests an association between the EGF 61*A/G polymorphism (rs4444903) and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent. Therefore, we performed a meta-analysis of several studies covering a large population to address this controversy. Methods PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between EGF 61*A/G polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results Eight studies were chosen in this meta-analysis, involving 1,304 HCC cases (1135 Chinese, 44 Caucasian and 125 mixed) and 2,613 controls (1638 Chinese, 77 Caucasian and 898 mixed). The EGF 61*G allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.29, 95% CI = 1.16–1.44, p<0.001), homozygote comparison (OR = 1.79, 95% CI = 1.39–2.29, p<0.001) and a recessive genetic model (OR = 1.34, 95% CI = 1.16–1.54, p<0.001), while patients carrying the EGF 61*A/A genotype had significantly lower risk of HCC than those with the G/A or G/G genotype (A/A vs. G/A+G/G, OR = 0.66, 95% CI = 0.53–0.83, p<0.001). Conclusion The 61*G polymorphism in EGF is a risk factor for hepatocarcinogenesis while the EGF 61*A allele is a protective factor. Further large and well-designed studies are needed to confirm this conclusion.

Adoptive immunotherapy for postoperative hepatocellular carcinoma: a systematic review.

The high risk of recurrence in post‐operative hepatocellular carcinoma (HCC) highlights the need for an effective adjuvant treatment. A systematic review of randomised controlled trials (RCTs) was performed to evaluate the clinical efficacy of adjuvant adoptive immunotherapy (AIT) for post‐operative HCC patients. Electronic (MEDLINE, EMBASE and Cochrane Library databases) and manual searches were conducted throughout May 2011 to identify RCTs evaluating postoperative AIT for patients with HCC. Methodological quality was assessed in accordance with the QUOROM statement. Four RCTs totalling 423 patients met the eligibility criteria. All RCTs reported significantly improved disease‐free survival rate or reduced recurrence rate after treating with adjuvant AIT (p < 0.05). The overall survival rates of AIT group are slightly higher than those of the control group in one study. Moreover, AIT was a safe treatment, with fever as the main adverse effects. This study adds to the evidence that postoperative HCC patients treated with adjuvant AIT show an improvement in disease‐free survival rate or recurrence rate.

Systematic review comparing the safety and efficacy of conventional and drug‐eluting bead transarterial chemoembolization for inoperable hepatocellular carcinoma

Conventional transarterial chemoembolization (cTACE) is widely used for treating patients with inoperable hepatocellular carcinoma (HCC). A variation on the technique based on drug‐eluting beads (DEB‐TACE) has recently entered the clinic, but trials of its safety and efficacy have given conflicting results. This systematic review aimed to gain a current, comprehensive picture of how DEB‐TACE compares with cTACE.