Le-Qun Li

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.

Evaluation of risk factors and clinicopathologic features for intrahepatic cholangiocarcinoma in Southern China: a possible role of hepatitis B virus.

BackgroundRecent efforts suggest an etiologic role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC) and the involvement of hepatic progenitor cell in ICC development, without definitive conclusions. This case-control study was undertaken to investigate risk factors for ICC, and clinicopathological features of HBV-associated ICC were analyzed.MethodsThe report comprised 98 patients with pathologically confirmed ICC and 196 healthy control subjects. Logistic regression was used to determine odds ratios and 95% confidence intervals. The sex and age distributions of HBV-related and unrelated ICC patients were compared respectively with those of 882 HBV-associated hepatocellular carcinoma patients from a random selection, and the clinicopathological data of 62 ICC patients with or without HBV infection undergoing surgical resection were compared.ResultsThere was an association between ICC and each of HBV infection, liver cirrhosis, hepatolithiasis, and liver fluke infestation with the odds ratios (95% confidence intervals) of 2.75 (1.27–5.95), 8.42 (2.50–28.37), 22.81 (7.16–72.68), and 3.55 (1.60–7.89), respectively, with a marked synergism of cirrhosis and HBV infection (20.67; 5.40–79.06). Compared with HBV-unrelated ICC patients, HBV-related ICC patients were more common in male and younger subjects, had a higher incidence of abnormal serum alfa-fetoprotein level, cirrhosis, and neutrophilic infiltration, and had a lower proportion of elevated carbohydrate antigen 19-9 (CA19-9) values.ConclusionsThe independent association of HBV infection with ICC, synergy between cirrhosis and HBV infection, and some clinicopathological similarities between HBV-related ICC and hepatocellular carcinoma suggests that both may share similar or common tumorigenic process and may possibly originate from malignant transformation of hepatic progenitor cell.

Hepatitis B virus infection contributes to oxidative stress in a population exposed to aflatoxin B1 and high-risk for hepatocellular carcinoma

Biomarkers of hepatitis B virus (HBV) infection, aflatoxin B1 (AFB1) exposure and oxidative stress were detected in 71 hepatocellular carcinoma (HCC) patients and 694 controls from southern China. Plasma level of AFB1-albumin-adducts (AAA) and protein carbonyl content (PCC) were significantly higher in the 71 HCC cases than in any age/gender matched HBV sero-status groups (p<0.001). HCC patients positive for the p53-249 G-T mutation had a marginally higher level of PCC than those negative for the mutation (p=0.077). HBV infection had a prominent influence on the association between AFB1 exposure and oxidative stress biomarkers in the controls. Our study indicates a significant contribution from HBV infection to oxidative stress in a population with AFB1 exposure which might substantially increase risk for HCC in this region.

Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging

Mn-based nanoparticles (NPs) have emerged as new class of probes for magnetic resonance imaging due to the impressive contrast ability. However, the reported Mn-based NPs possess low relaxivity and there are no immunotoxicity data regarding Mn-based NPs as contrast agents. Here, we demonstrate the ultrahigh relaxivity of water protons of 8.26 mM−1s−1 from the Mn3O4 NPs synthesized by a simple and green technique, which is twice higher than that of commercial gadolinium (Gd)-based contrast agents (4.11 mM−1s−1) and the highest value reported to date for Mn-based NPs. We for the first time demonstrate these Mn3O4 NPs biocompatibilities both in vitro and in vivo are satisfactory based on systematical studies of the intrinsic toxicity including cell viability of human nasopharyngeal carcinoma cells, normal nasopharyngeal epithelium, apoptosis in cells and in vivo immunotoxicity. These findings pave the way for the practical clinical diagnosis of Mn based NPs as safe probes for in vivo imaging.

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.

Cancer stem cell markers correlate with early recurrence and survival in hepatocellular carcinoma

AIM To investigate whether expression of cancer stem cell (CSC) markers is associated with recurrence and survival in hepatocellular carcinoma (HCC) patients. METHODS A consecutive series of 90 HCC patients who underwent curative hepatectomy between April 2007 and April 2009 were analyzed. Of the 90 patients, 38 (42%) experienced recurrence within two years of surgery. To adjust for baseline differences between this early recurrence group and the other patients, propensity-score matching was used to generate 25 pairs of patients. Immunohistochemistry was used to compare expression of CD133, CD90, and epithelial cell adhesion molecule (EpCAM) in liver tissues from propensity score-matched patients and from 10 healthy adults. Associations of the three markers with HCC, clinicopathological characteristics, early recurrence, and survival time were explored. RESULTS The expression of all three CSC markers was significantly higher in HCC tissue than in healthy liver tissue (P < 0.001 for all). Among the HCC clinicopathology characteristics examined, the absence of tumor capsule was associated with CD133 expression (P = 0.005); higher histopathology grade and larger tumor size were associated with CD90 expression (P = 0.010 and 0.034, respectively); and elevated serum alpha-fetoprotein levels were associated with EpCAM expression (P = 0.021). Expression of CD90 and EpCAM was significantly higher in the early recurrence group than in other patients (P = 0.001 and 0.045, respectively), whereas CD133 expression was not significantly different between the two groups (P = 0.440). Multivariate analysis identified only CD90 expression as significantly associated with early recurrence. Log-rank analysis identified expression of both CD90 and EpCAM as significantly associated with survival time of HCC patients. Cox regression identified EpCAM expression as an independent predictor of survival time. CONCLUSION Expression of CD133, CD90, and EpCAM CSC markers may be linked to HCC tumor onset and/or progression. In addition, EpCAM expression is associated with shorter survival time, while CD90 expression is associated with early HCC recurrence.