Wen-Feng Gong

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.

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.

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.

Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary hospital in China: A real-world study

The current clinical reality of tumor stages and primary treatments of hepatocellular carcinoma (HCC) is poorly understood. This study reviewed the distribution of tumor stages and primary treatment modalities among a large population of patients with primary HCC. Medical records of patients treated between January 2003 and October 2013 for primary HCC at our tertiary hospital in China were retrospectively reviewed. A total of 6241 patients were analyzed. The distribution of Barcelona Clinic Liver Cancer (BCLC) stages was as follows: stage 0/A, 28.9%; stage B, 16.2%; stage C, 53.6%; stage D, 1.3%. The distribution of Hong Kong Liver Cancer (HKLC) stages was as follows: stage I, 8.4%; stage IIa, 1.5%; stage IIb, 29.0%; stage IIIa, 10.0%; stage IIIb, 33.6%; stage IVa, 3.4%; stage IVb, 2.5%; stage Va, 0.2%; stage Vb, 11.4%. The most frequent therapy was hepatic resection for patients with BCLC-0/A/B disease, and transarterial chemoembolization for patients with BCLC-C disease. Both these treatments were the most frequent for patients with HKLC I to IIIb disease, while systemic chemotherapy was the most frequent first-line therapy for patients with HKLC IVa or IVb disease. The most frequent treatment for patients with HKLC Va/Vb disease was traditional Chinese medicine. In conclusion, Prevalences of BCLC-B and -C disease, and of HKLC I to IIIb disease, were relatively high in our patient population. Hepatic resection and transarterial chemoembolization were frequent first-line therapies.

Association between age and overall survival of patients with hepatocellular carcinoma after hepatic resection.

The suitability of hepatic resection for older patients remains controversial. This study aimed to investigate whether age influences overall survival of patients with hepatocellular carcinoma (HCC) after resection.

Association of the miR-196a2 C>T and miR-499 A>G polymorphisms with hepatitis B virus-related hepatocellular carcinoma risk: an updated meta-analysis

Background This study meta-analyzed data on the possible association of the miR-196a2 C>T (rs11614913) and miR-499 A>G (rs3746444) polymorphisms with risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods Databases in PubMed, EMBASE, Web of Science, China BioMedicine, and Google Scholar were systematically searched to identify relevant studies. Meta-analyses were performed to examine the association of the miR-196a2 C>T and miR-499 A>G polymorphisms with HBV-related HCC risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results A total of 13 studies involving 3,964 cases and 5,875 healthy controls were included. Random-effect meta-analysis showed that the T allele and TT genotype of miR-196a2 C>T were associated with significantly lower HBV-related HCC risk (allelic model, OR =0.84, 95% CI =0.71–0.99, P=0.04; homozygous model, OR =0.68, 95% CI =0.47–0.98, P=0.04). In contrast, miR-499 A>G showed no significant association with HBV-related HCC risk in either overall pooled analysis or ethnic subgroup analysis according to any of the four genetic models. Based on analysis of ethnic subgroups, neither miR-196a2 C>T nor miR-499 A>G was significantly associated with risk of HBV-related HCC in Chinese population. Conclusion The polymorphism miR-196a2 C>T, but not miR-499 A>G, may be associated with decreased HBV-related HCC risk. These conclusions should be verified in large, well-designed studies.

Effects of antiviral therapy on post-hepatectomy HBV reactivation and liver function in HBV DNA-negative patients with HBV-related hepatocellular carcinoma

The ability of antiviral therapy to reduce risk of post-hepatectomy hepatitis B virus (HBV) reactivation in patients negative for viral DNA is unclear. This prospective study involved 174 consecutive patients with hepatitis B virus related hepatocellular carcinoma who were negative for hepatitis B virus DNA in serum and who underwent hepatic resection. Hepatitis B virus reactivation occurred in 30 patients in the non-antiviral group (27.8%) but in only 2 patients in the antiviral group (3.0%, P < 0.001). Based on multivariate analysis, risk of hepatitis B virus reactivation was associated with minor hepatectomy and absence of antiviral therapy. Liver function indicators at one week after resection did not differ significantly between the two groups, or between patients who experienced hepatitis B virus reactivation or not. Nevertheless, alanine aminotransferase and albumin at 1 month after resection were significantly higher in the antiviral group than in the non-antiviral group, and they were significantly higher in patients who did not experience hepatitis B virus reactivation than in those who did. Therefore, patients with hepatitis B virus related hepatocellular carcinoma face substantial risk of hepatitis B virus reactivation after hepatectomy, even if they are negative for viral DNA at baseline. Antiviral therapy can reduce the risk of reactivation, helping improve liver function after surgery. (Clinicaltrials.gov registration number: NCT02829359).

Is drug‐eluting‐bead transcatheter arterial chemoembolization (TACE) associated with better tumor response than conventional TACE in a meta‐analysis?: Authors’ reply

Dear Editor, We thank Kodama and coworkers for their letter on our review, which was critical of drug-eluting-bead transarterial chemoembolization (DEB-TACE) possibly bringing better tumor response than conventional TACE (cTACE) for inoperable hepatocellular carcinoma. Our review studied the safety and efficiency of DEB-TACE compared with cTACE depending on six trials (Ferrer et al., Lammer et al., Sacco et al., Malenstein et al., Recchia et al. and Golfieri et al.). We drew the conclusion that althoughDEB-TACE could not bring better overall survival, it brings better tumor response. However, Kodama et al. pointed out that DEB-TACE was not superior to cTACE (risk ratio [RR]=1.00, 95% confidence interval [CI] =0.83–1.21, P=0.194) on tumor response. We have re-analyzed original data from all the included studies. We acknowledge the reference errors in Supplement Table 2 of our review (revised data are shown as Table 1). In our review, we analyzed objective response (OR) rate (OR= complete response [CR]+partial response [PR]) as outcome, which was described in the section of “Types of outcome measures” and “Methods” (p. 191). Actually, OR, CR and stable disease rate were described in the five original studies (Ferrer et al., Lammer et al., Sacco et al., Malenstein et al. and Golfieri et al.). In our review, stable disease rate was not calculated. Our results of better OR were supported by another recent meta-analysis, in which the definition of OR was the same as ours. This metaanalysis included seven studies involving 700 participants. However, the data on stable disease rate was included when Kodama et al. calculated tumor response. Here, we re-analyzed the tumor response as CR and PR, respectively. Although on the outcome of CR, no significance was found between cTACE and DEB-TACE groups (RR=0.86, 95% CI=0.70–1.06), patients in the DEB-TACE group had significantly better tumor response on PR (RR=1.30, 95% CI=1.01–1.69). One of the included studies by Malenstein et al. recruited 30 patients. However, only 25 patients’ data was analyzed in the original study. In our review, intention-to-treat analysis was performed including all 30 recruited patients. Thismight have led to differences with the results of Kodama et al.

Optimizing stage of single large hepatocellular carcinoma: A study with subgroup analysis by tumor diameter

Abstract This study aims to refine the designation for single hepatocellular carcinoma (HCC) >5 cm by comparing the postresection prognosis of these patients with those who have a single-tumor ⩽5 cm and those with stage B. Patients with a single-tumor were classified into subgroups based on diameter. Of the 1132 patients analyzed, 426 had a single-tumor >2 and ⩽5 cm; 229, a single-tumor >5 and ⩽8 cm; 52, a single-tumor >8 and < 10 cm; 150, a single-tumor ≥10 cm; and 275, stage B. Hospital mortality and complications increased with tumor size among the single-tumor subgroups and median survival decreased with increasing of tumor size. Overall survival (OS) among patients with a single-tumor >5 cm was significantly lower than among patients with a single-tumor >2 and ⩽5 cm (P ⩽ .001), but significantly higher than among patients with clearly stage B (P ⩽ .001). Patients with a single-tumor >5 and ⩽8 cm showed lower OS than patients with a single-tumor >2 and ⩽5 cm (P < .001). Patients with a single-tumor >8 and <10 cm or a single-tumor ≥10 cm showed lower OS than patients with a single-tumor >5 and ⩽8 cm (P = .033 and .006), and similar OS to patients with stage B (P = .323). Patients with a single-tumor >5 and ⩽8 cm may be assigned to a new stage between early and intermediate. Patients with a single-tumor >8 cm may be assigned to intermediate stage.