Appropriate treatment strategies improve survival of hepatocellular carcinoma patients with portal vein tumor thrombus

AIM:To evaluate the survival benefits of different treatment strategies for hepatocellular carcinoma(HCC)patients with portal vein tumor thrombus(PVTT)and to determine the prognosis factors.METHODS:Between 2007 and 2009,338 HCC patients treated for PVTT were retrospectively studied.The patients were divided into 4 groups that underwent different treatments:the conservative treatment group(n=75),the transarterial chemoembolization(TACE)group(n=86),the hepatic resection group(n=90),and the hepatic resection associated with postoperative TACE group(n=87).Survival rates were determined using the Kaplan-Meier method and differences between the groups were identified through log-rankanalysis.Cox’s proportional hazard model was used to identify the risk factors for survival.RESULTS:The mean survival periods for patients in the conservative treatment,TACE,hepatic resection and hepatic resection associated with postoperative TACE groups were 3.8,7,8.2 and 15.1 mo,respectively.Significant differences were observed in the survival rates.For the surgical resection associated with postoperative TACE group,the survival rates after 1,2 and3 years were 49%,37%and 19%,respectively.These results were significantly higher than those of the other groups(P<0.05).Meanwhile,the 1,2 and 3 year survival rates for the surgical resection group were 28%,20%and 15%,whereas those for the TACE group were17.5%,0%and 0%,respectively.These values significantly increased after hepatic resection compared with those after TACE(P<0.05).CONCLUSION:Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and results in high hepatic functional reserve.For patients who can tolerate the procedure,postoperative TACE is necessary to prevent recurrence and prolong the survival period.

Blood neutrophil-lymphocyte ratio predicts survival after hepatectomy for hepatocellular carcinoma: A propensity score-based analysis

AIM: To investigate whether an elevated preoperative neutrophil-to-lymphocyte ratio(NLR) can predict poor survival in patients with hepatocellular carcinoma(HCC).METHODS: We retrospectively reviewed 526 patients with HCC who underwent surgery between 2004 and 2011.RESULTS: Preoperative NLR ≥ 2.81 was an independent predictor of poor disease-free survival(DFS, P < 0.001) and overall survival(OS, P = 0.044). Compared with patients who showed a preoperative NLR < 2.81 and postoperative increase, patients who showed preoperative NLR ≥ 2.81 and postoperative decrease had worse survival(DFS, P < 0.001; OS, P < 0.001). Among patients with preoperative NLR ≥ 2.81, survival was significantly higher among those showing a postoperative decrease in NLR than among those showing an increase(DFS, P < 0.001; OS, P < 0.001). When elevated, alpha-fetoprotein(AFP) provided no prognostic information, and so preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS whenever AFP levels are low or high.CONCLUSION: Preoperative NLR ≥ 2.81 may be an indicator of poor DFS and OS in patients with HCC undergoing surgery. Preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS when elevated AFP levels provide no prognostic information.

Comprehensive treatments for hepatocellular carcinoma with tumor thrombus in major portal vein

AIM: To evaluate the efficacy of transcatheter arterial chemoembolisation(TACE) compared with surgical intervention and sorafenib for treatment of hepatocellular carcinoma(HCC) in patients with tumor thrombus extending to the main portal vein.METHODS: From 2009 to 2013, a total of 418 HCC patients with tumor thrombus extending to the main portal vein were enrolled in this study and divided into four groups. These groups underwent different treatments as follows: TACE(n = 307), surgical intervention(n = 54), sorafenib(n = 15) and palliativetreatment(n = 42). Overall survival rates were determined by Kaplan-Meier method, and differences between the groups were identified through log-rank analysis. Cox's proportional hazard model was used to identify the risk factors for survival.RESULTS: The mean survival periods for patients in the TACE, surgical intervention, sorafenib and palliative treatment groups were 10.39, 4.13, 5.54 and 2.82 mo, respectively. For the TACE group, the 3-, 6-, 12-and 24-mo survival rates were 94.1%, 85.9%, 51.5% and 0.0%, respectively. The corresponding rates were 60.3%, 22.2%, 0.0% and 0.0% for the surgical intervention group and 50.9%, 29.5%, 0.0% and 0.0% for the sorafenib group. Evidently, the results in the TACE group were significantly higher than those in the other groups(P < 0.0001). Furthermore, no significant difference among survival rates was observed between TACE with/without sorafenib(10.22 mo vs 10.52 mo, P = 0.615). No significant difference in survival rates was also found among the surgical intervention, sorafenib and palliative treatment groups(P > 0.05). These values significantly increased after TACE with/without sorafenib compared with other treatments(P < 0.05).CONCLUSION: For HCC patients with tumor thrombus extending to the main portal vein, TACE can yield a higher survival rate than surgical intervention or sorafenib treatment.

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 April2007 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.

Antiviral therapy for hepatitis B virus-related hepatocellular carcinoma after radical hepatectomy

Objective:To assess the effect of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)after radical hepatectomy.Methods:A total of 478 HBV-related HCC patients treated by radical hepatectomy were retrospectively collected.Patients in the treatment group(n=141)received postoperative lamivudine treatment(100 mg/d),whereas patients in the control group(n=337)did not.Recurrence-free survival(RFS)rates,overall survival(OS)rates,treatments for recurrent HCC and cause of death were compared between the two groups.Propensity score matching(PSM)analysis was also conducted to reduce confounding bias between the two groups.Results:The 1-,3-,and 5-year RFS rates didn't significantly differ between the two groups(P=0.778);however,the 1-,3-,and 5-year OS rates in the treatment group were significantly higher than those in the control group(P=0.002).Similar results were observed in the matched data.Subgroup analysis showed that antiviral treatment conferred a significant survival benefit for Barcelona Clinical Liver Cancer stage A/B patients.Following HCC recurrence,more people in the treatment group were able to choose curative treatments than those in the control group(P=0.031).For cause of death,fewer people in the treatment group died of liver failure than those in the control group(P=0.041).Conclusion:Postoperative antiviral therapy increases chances of receiving curative treatments for recurrent HCC and prevents death because of liver failure,thereby significantly prolonging OS,especially in early-or intermedian-stage tumors.

Cyclooxygenase-2 expression is associated with initiation of hepatocellular carcinoma, while prostaglandin receptor-1 expression predicts survival

AIM to determine whether cyclooxygenase-2(COX-2) and prostaglandin E1 receptor(EP1) contribute to disease and whether they help predict prognosis.METHODS We retrospectively reviewed the records of 116 patients with hepatocellular carcinoma(HCC) who underwent surgery between 2008 and 2011 at our hospital. Expression of COX-2 and EP1 receptor was examined by immunohistochemistry of formalin-fixed, paraffinembedded tissues using polyclonal antibodies. Possible associations between immunohistochemical scores and survival were determined.RESULTS Factors associated with poor overall survival(OS) were alpha-fetoprotein > 400 ng/m L, tumor size ≥ 5 cm, and high EP1 receptor expression, but not high COX-2 expression. Disease-free survival was not significantly different between patients with low or high levels of COX-2 or EP1. COX-2 immunoreactivity was significantly higher in well-differentiated HCC tissues(Edmondson grade Ⅰ-Ⅱ) than in poorly differentiated tissues(Edmondson grade Ⅲ-Ⅳ)(P = 0.003). EP1 receptor immunoreactivity was significantly higher in poorly differentiated tissue than in well-differentiated tissue(P = 0.001).CONCLUSION COX-2 expression appears to be linked to early HCC events(initiation), while EP1 receptor expression may participate in tumor progression and predict survival.

Antiviral therapy for hepatitis B virus-related hepatocellular carcinoma after surgery: A comment for moving forward

Recurrence rate of hepatocellular carcinoma remains quite high even after surgery,and no postoperative therapies have been definitively shown to prevent hepatocellular carcinoma recurrence.A previous study showed that therapy with nucleos(t)ide analogues given to such patients after surgery significantly improved survival.However,many questions still exist about the usage of nucleos(t)ide analogues for patients with hepatocellular carcinoma after surgery.

Adjuvant sorafenib in hepatocellular carcinoma: A cautionary comment of STORM trial

Recurrence rate of hepatocellular carcinoma(HCC) is very high even after curative surgery, and no postoperative therapies have been definitively shown to prevent HCC recurrence. Sorafenib is proved to be effective for advanced HCC by two large randomized controlled trials in 2008 and 2009. Therefore it stands to reason to expect that adjuvant sorafenib may improve post-surgery outcomes of patients with HCC. However, many questions still exist about the value of sorafenib for patients with HCC after surgery or transarterial chemoembolization. In this editorial, we complehensively reviewed the safety and efficacy of adjuvant sorafenib for patients with hepatocellar carcinoma after surgery or transarterial chemoembolization. We emphasized the positive and negative role of sorafenib.

Potential Role and Clinical Value of PPP2CA in Hepatocellular Carcinoma

Background and Aims:Protein phosphatase 2A(PP2A)is associated with many cancers.This study aimed to clarify whether PPP2CA,which encodes the alpha isoform of the catalytic subunit of PP2A,plays a role in hepatocellular carcinoma(HCC)and to identify the potential underlying molecular pathways.Methods:Based on bioinformatics,public databases and our in-house RNA-Seq database,we analyzed the clinical value and molecular mechanism of PPP2CA in HCC.Results:Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database,the Gene Expression Omnibus database and our in-house RNA-Seq database.PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues(standardized mean difference:0.69,95%confidence interval[CI]:0.50–0.89).PPP2CA expression was able to differentiate HCC from non-HCC,with an area under the summary receiver operator characteristic curve of 0.79(95%CI:0.75–0.83).Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues.High PPP2CA expression in HCC patients was associated with shorter overall,progression-free and disease-free survival.Potential molecular pathways through which PPP2CA may be involved in HCC were determined using miRWalk 2.0 as well as analysis of Gene Ontology categories,Kyoto Encyclopedia of Genes and Genomes pathways,and protein-protein interaction networks.Conclusions:PPP2CA is up-regulated in HCC and higher expression correlates with worse prognosis.PPP2CA shows potential as a diagnostic marker for HCC.Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs,pathways and hub genes identified in this study.

Controversies of hepatectomy and adjuvant therapy for hepatocellular carcinoma: moving forward

Due to the prevelence of hepatitis B virus(HBV)and hepatitis C virus(HCV),occurrence of hepatocellular carcinoma(HCC)is increasing in many countries/regions,including China[1].