Drug-eluting bead transarterial chemoembolization (TACE) exhibits superior efficacy and equal tolerance to conventional TACE in hepatocellular carcinoma patients with conventional TACE history

ObjectiveMultiple conventional transarterial chemoembolization (cTACE) procedures would cause treatment resistance in hepatocellular carcinoma (HCC) patients, whether drug-eluting bead transarterial chemoembolization (DEB-TACE) would resolve this issue is a necessary topic. Thus, this study aimed to compare the efficacy and safety between DEB-TACE and cTACE in HCC patients with cTACE treatment history.MethodsTotally, 134 HCC patients with cTACE treatment history were retrospectively reviewed. They were categorized into DEB-TACE group (N = 70) and cTACE group (N = 64) based on the current treatment they received.ResultsAfter 1-month treatment, DEB-TACE group exhibited an elevated objective response rate (ORR) (71.9% vs. 47.3%, P = 0.008) while similar disease control rate (DCR) (93.0% vs. 81.8%, P = 0.074) compared to cTACE group. Besides, after 3-month treatment, DEB-TACE group also displayed higher ORR (68.4% vs. 44.1%, P = 0.038) and DCR (81.6% vs. 58.8%, P = 0.034) compared to cTACE group. Furthermore, the median progression-free survival (PFS) (11.5 months vs. 6.5 months P = 0.014) and overall survival (OS) (18.5 months vs. 13.0 months, P = 0.025) were longer in DEB-TACE group compared to cTACE group. Moreover, DEB-TACE (vs. cTACE) independently correlated with prolonged PFS (P = 0.021) and OS (P = 0.017) after adjustment by multivariate Cox's regression. Besides, most of liver function indexes were similar before and after treatment between these two groups. Also, the commonly observed adverse events were pain, fever, nausea/vomiting and blood pressure elevation with similar incidence between these two groups (all P > 0.050).ConclusionDEB-TACE exhibits superiority over cTACE in HCC patients with cTACE treatment history.     

Comparison of DEB-TACE and cTACE for the initial treatment of unresectable hepatocellular carcinoma beyond up-to-seven criteria: A single-center propensity score matching analysis

PurposeTo evaluate clinical outcomes of drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres microspheres and conventional TACE (cTACE) as the initial treatment in patients with unresectable hepatocellular carcinoma (HCC) beyond up-to-seven criteria.MethodsThe study retrospectively assessed the medical records of HCC patients beyond up-to-seven criteria who received the initial treatment of DEB-TACE or cTACE from June 2016 to December 2019 in our institution. To reduce the patient selection bias, propensity score matching (PSM) analysis was used. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were compared between the two groups. In addition, prognostic factors affecting PFS and OS were analyzed by univariate and multivariate methods.ResultsA total of 312 eligible HCC patients were included in the study, including 140 patients in the DEB-TACE group and 172 patients in the cTACE group. 110 patients were chosen in each group after PSM analysis and there were no significant differences in baseline characteristics (P > 0.05). Before PSM analysis, DEB-TACE had better ORR and DCR compared to cTACE group (P < 0.05). After PSM analysis, the ORR for DEB-TACE group was still higher than that for cTACE group, while no significant difference in the DCR between the two groups. In addition, DEB-TACE group had better survival benefits than cTACE group before PSM analysis (mPFS: 11.5 months vs 9.0 months, P < 0.001; mOS: 24.0 months vs 19.2 months, P = 0.045). Similarly, after PSM analysis, the median PFS and OS in the DEB-TACE group were still higher than that in the cTACE group (mPFS: 11.1 months vs 9.0 months, P = 0.015; mOS: 25.0 months vs 19.0 months, P = 0.030). Further, the univariate and multivariate analysis indicated that DEB-TACE treatment was a positive prognostic factor for PFS and OS.ConclusionDEB-TACE with CalliSpheres microspheres might be an effective and safe treatment for patients with unresectable HCC beyond up-to-seven criteria.     

Comparative effectiveness of traditional chemoembolization with or without sorafenib for hepatocellular carcinoma

AIM: To compare the overall survival (OS) and progression-free survival (PFS) with associated adverse events (AE) in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) + sorafenib vs TACE alone. METHODS: In this retrospective cohort study we collected data on all consecutive patients with a diagnosis of unresectable HCC between 2007 and 2011 who had been treated with TACE + sorafenib or TACE alone. We hypothesized that the combination therapy is superior to TACE alone in improving the survival in these patients. Data extracted included patient’s demographics, etiology of liver disease, histology of HCC, stage of liver disease with respect to model of end stage liverdisease score and Child-Turcotte-Pugh (CTP) classification and Barcelona Clinic Liver Cancer (BCLC) staging for HCC. Computed tomography scan findings, alpha fetoprotein levels, number of treatments and related AE were also recorded and analyzed. RESULTS: Of the 43 patients who met inclusion criteria, 13 were treated with TACE + sorafenib and 30 with TACE alone. There was no significant difference in median survival: 20.6 mo (95%CI: 13.4-38.4) for the TACE + sorafenib and 18.3 mo (95%CI: 11.8-32.9) for the TACE alone (P = 0.72). There were also no statistically significant differences between groups in OS (HR = 0.82, 95%CI: 0.38-1.77; P = 0.61), PFS (HR = 0.93, 95%CI: 0.45-1.89; P = 0.83), and treatment-related toxicities (P = 0.554). CTP classification and BCLC staging for HCC were statistically significant (P = 0.001, P = 0.04 respectively) in predicting the survival in patients with HCC. The common AE observed were abdominal pain, nausea, vomiting and mild elevation of liver enzymes. CONCLUSION: Combination therapy with TACE + sorafenib is safe and equally effective as TACE alone in patients with unresectable HCC. CTP classification and BCLC staging were the significant predictors of survival. Future trials with large number of patients are needed to further validate this observation.     

Best radiological response to trans‐arterial chemoembolization for hepatocellular carcinoma does not imply better outcomes

IntroductionRegional therapy with trans‐arterial chemoembolization (TACE) is a common treatment for unresectable hepatocellular carcinoma (HCC). Outcomes were examined in patients with the best radiological response (BR) after the initial TACE.MethodsThis was a retrospective cohort study of patients who underwent TACE as the initial treatment for HCC between the years 2000 and 2010. BR was defined as complete disappearance of the tumour or no enhancement with contrast on the first cross‐sectional imaging study after the initial TACE.ResultsSeventy‐eight out of 104 total consecutive patients were identified with the potential for a BR to TACE therapy for unresectable HCC, and 24 met the criteria for BR. Patients with BR had a median survival of 12.8 months (2.2–54.9) compared with 18.9 months(1.3–56.7) for the entire cohort (P= 0.313). The median time to progression was 10.6 months (1.2–24.3) in the BR group and 3.2 months (0.7–49.2) in the patients without a BR (P= 0.003).DiscussionBR to initial TACE for unresectable HCC is associated with comparable survival to those without BR in spite of a longer time to cancer progression. It may be reasonable to consider further therapy such as repeat TACE or biological/systemic therapy in patients with HCC even when the radiological response to the initial TACE is favourable.     

Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma

AIM: To compare radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA monotherapy in hepatocellular carcinoma (HCC). METHODS: We searched PubMed, Medline, Embase and Chinese databases (CBMdisc and Wanfang data) for randomized controlled trails comparing RFA plus TACE and RFA alone for treatment of HCC from January 2000 to December 2012. The overall survival rate, re-currence-free survival rate, tumor progression rate, and safety were analyzed and compared. The analysis was conducted on dichotomous outcomes and the standard meta-analytical techniques were used. Pooled odds ratios (ORs) with 95%CIs were calculated using either the fixed-effects or random-effects model. For each meta-analysis, the χ2 and I2 tests were first calculated to assess the heterogeneity of the included trials. For P<0.05 and I 2>50%, the assumption of homogeneity was deemed invalid, and the random-effects model wasused; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted us-ing Review manager (version 4.2.2.) from the Cochrane collaboration. RESULTS: Eight randomized controlled trials were identified as eligible for inclusion in this analysis and included 598 patients with 306 treated with RFA plus TACE and 292 with RFA alone. Our data analysis indicated that RFA plus TACE was associated a sig-nificantly higher overall survival rate (OR 1-year=2.96, 95%CI: 1.84-7.74, P<0.001; OR 2-year=3.72, 95%CI: 1.24-11.16, P=0.02; OR 3-year=2.65, 95%CI: 1.81-3.86, P<0.001) and recurrence-free survival rate (OR 3-year=3.00, 95%CI: 1.75-5.13, P<0.001; OR 5-year=2.26, 95%CI: 1.43-3.57, P=0.0004) vs that of RFA alone. The tumor progression rate in patients treated with RFA alone was higher than that of RFA plus TACE (OR=0.60, 95%CI: 0.42-0.88, P=0.008) and there was no significant difference on major complications between two different kinds of treatment (OR=1.20, 95%CI: 0.31-4.62, P=0.79). Additionally, the meta-analysis data of subgroups revealed that the     

Transarterial chemoembolization: Evidences from the literature and applications in hepatocellular carcinoma patients

Transarterial chemoembolization (TACE) is the current standard of care for patients with large or multinodular hepatocellular carcinoma (HCC), preserved liver function, absence of cancer-related symptoms and no evidence of vascular invasion or extrahepatic spread (i.e., those classified as intermediate stage according to the Barcelona Clinic Liver Cancer staging system). The rationale for TACE is that the intra-arterial injection of a chemotherapeutic drug such as doxorubicin or cisplatin followed by embolization of the blood vessel will result in a strong cytotoxic effect enhanced by ischemia. However, TACE is a very heterogeneous operative technique and varies in terms of chemotherapeutic agents, treatment devices and schedule. In order to overcome the major drawbacks of conventional TACE (cTACE), non-resorbable drug-eluting beads (DEBs) loaded with cytotoxic drugs have been developed. DEBs are able to slowly release the drug upon injection and increase the intensity and duration of ischemia while enhancing the drug delivery to the tumor. Unfortunately, despite the theoretical advantages of this new device and the promising results of the pivotal studies, definitive data in favor of its superiority over cTACE are still lacking. The recommendation for TACE as the standard-of-care for intermediate-stage HCC is based on the demonstration of improved survival compared with best supportive care or suboptimal therapies in a meta-analysis of six randomized controlled trials, but other therapeutic options (namely, surgery and radioembolization) proved competitive in selected subsets of intermediate HCC patients. Other potential fields of application of TACE in hepato-oncology are the pre-transplant setting (as downstaging/bridging treatment) and the early stage (in patients unsuitable to curative therapy). The potential of TACE in selected advanced patients with segmental portal vein thrombosis and preserved liver function deserves further reports.     

Therapeutic Efficacy of Sorafenib in Patients with Hepatocellular Carcinoma Recurrence After Liver Transplantation: A Systematic Review and Meta-Analysis

Background: Hepatocellular carcinoma (HCC) recurrence is still threatening patient survival after liver transplantation (LT). The efficacy and safety of sorafenib in the setting of post-LT recurrence are still equivocal. This study aims to disclose the efficacy and safety profile of sorafenib in treating post-LT HCC recurrence.Materials and Methods: Electronic databases were searched to retrieve relevant publications suitable for inclusion. Data from 23 studies containing 411 patients were analyzed. The primary outcome of interest was 1-year survival rate after sorafenib treatment, and the secondary endpoints included median overall survival (OS), time to progression (TTP), treatment response, and adverse events.Results: Patients with HCC recurrence after LT treated with sorafenib achieved a 1-year survival rate of 56.8%, with a median OS of 12.8 months and a median TTP of 6.0 months. Univariate logistic regression analysis showed that male gender (P = .048), TTP (P = .021), median duration of sorafenib (P = .021), diarrhea (P = .027), fatigue (P = .044), and partial response (P = .026) were associated with a better 1-year survival rate. In addition, sorafenib exerted a significant superior effect on OS compared with best supportive care in the setting of untreatable post-LT HCC recurrence.Conclusions: Based on the results of this meta-analysis, sorafenib therapy seems to be safe and feasible and exhibits survival benefit in patients with post-LT HCC recurrence. However, prospective randomized controlled trials with larger sample sizes and more rigorous study design are required to confirm the efficacy of sorafenib.     

Comparative study of cisplatin and epirubicin in transcatheter arterial chemoembolization for hepatocellular carcinoma

Aim: Transcatheter arterial chemoembolization (TACE) is an established treatment for unresectable hepatocellular carcinoma (HCC). However, it is unclear which chemotherapeutic agent should be selected for TACE. The aim of this study was to compare the efficacy of cisplatin (CDDP) with that of epirubicin (EPI) in TACE for patients with unresectable or relapsed HCC. Methods: We performed a historical cohort study involving 131 patients treated with a first TACE, defined as either an initial treatment for previously untreated HCC or a first treatment for relapsed HCC after curative resections or ablations. Efficacy was estimated as the response rate (RR) and it was adjusted for the confounding factors that were defined in this study. Results: The RR were 62.5% (20/32) for the first TACE with CDDP and 51.5% (51/99) for that with EPI. In the adjusted analysis for a history of hepatectomy, percutaneous treatment combined with TACE and tumor factors, the odds ratio was 1.72 (95% confidence interval [CI] = 0.70–4.48). However, a test for interaction between the number of tumors and the chemotherapeutic agent was statistically significant (P = 0.016). In multiple HCC, the RR were 66.7% (10/17) for CDDP and 39.6% (30/46) for EPI. The odds ratio was 4.11 (95% CI = 1.14–17.2). Conclusion: CDDP may be more effective than EPI in TACE for multiple HCC. A randomized controlled study is needed to clarify the efficacy of CDDP in TACE in patients with multiple HCC.     

Conventional vs drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma

Transarterial chemoembolization(TACE) is the current standard of therapy for patients with intermediatestage hepatocellular carcinoma(HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE(cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drugeluting beads(DEBs) have been imposed as novel drugdelivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEBTACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.     

The addition of camrelizumab is effective and safe among unresectable hepatocellular carcinoma patients who progress after drug-eluting bead transarterial chemoembolization plus apatinib therapy

ObjectiveCamrelizumab synergizes with apatinib or transarterial chemoembolization via tumor immunity and chemosensitivity. This study aimed to investigate the efficacy and safety of camrelizumab plus apatinib with or without drug-eluting bead transarterial chemoembolization (DEB-TACE) in unresectable hepatocellular carcinoma (HCC) patients after progression to DEB-TACE plus apatinib.MethodsEighty-nine unresectable HCC patients accepted previous DEB-TACE plus apatinib therapy, then further received second-line camrelizumab plus apatinib with or without DEB-TACE treatment. Treatment responses were calculated at 3 months (M3) and 6 months (M6). Survival and treatment-related adverse events were documented.ResultsObjective response rate and disease control rate were 39.3% and 80.9% at M3; meanwhile, they were 22.4% and 54.1% at M6. Furthermore, the median progression-free survival (PFS) (95% confidence interval (CI)) was 7.0 (6.2-7.8) months with a 1-year PFS rate of 18.4%; the median overall survival (OS) (95% CI) was 17.0 (15.3-18.7) months with a 1-year OS rate of 73.9%. Multivariable Cox's proportional hazards regression analysis presented that 3-4 times (vs. 0 time) of DEB-TACE, apatinib dose duration> 4 months, and camrelizumab dose duration> 5 months independently predicted longer PFS (all P<0.05); meanwhile, declined ECOG PS score, new lesions as progression pattern, 1-2 and 3-4 times (vs. 0 time) of DEB-TACE, apatinib dose duration> 4 months independently predicted prolonged OS (all P<0.05). Moreover, treatment-related adverse events mainly included grade 1-2 fever, gastrointestinal reaction, fatigue, hand-foot skin reaction, and hypertension.ConclusionAfter progression to DEB-TACE plus apatinib treatment, the addition of camrelizumab is effective and safe among unresectable HCC patients.     

Nine-year experience of doxorubicin-eluting beads chemoembolization for hepatocellular carcinoma

BACKGROUND: Chemoembolization with doxorubucin-eluting beads (DEB) has been used to treat hepatocellular carcinoma (HCC) since 2007. This study compared the efifcacy and sur-vival between transarterial chemoembolization (TACE) with DEB and conventional approach (cTACE) in HCC treatment.
METHODS: This retrospective case-control study compared the overall survival and tumor response of HCC patients to cTACE (n=190) and DEB (n=143) by the reassessment of com-puted tomography and serum alpha-fetoprotein (AFP). Mul-tivariate analysis was used to determine the factors affecting tumor response.
RESULTS: The median post-treatment to pre-treatment AFP level was 0.8 for a DEB session (n=258) and 1.0 for a cTACE session (n=452), showing a signiifcantly greater decrease in AFP after DEB (P<0.05). More patients in the DEB group achieved objective response (complete and partial) compared with those in the cTACE group (P<0.05). Objective tumor re-sponse after DEB vs cTACE was 34.8% vs 15.4% in 0-3 months (P=0.001), 37.1% vs 20.0% in 3-6 months (P<0.05), and 50.0%vs 30.0% in 6-12 months (P=0.093). DEB predicted a 3.604 times odds of achieving at least one objective tumor response in a patient when compared to cTACE (P<0.0001). The median survival from ifrst transcatheter therapy of patients having undergone at least once DEB was 12.53 months, while those having received cTACE only was 10.53 months (P=0.086). A tendency of improved survival appeared to maintain until >80 months after the ifrst TACE session in the DEB group.
CONCLUSION: DEB is a safe alternative to cTACE in HCC pa-tients with better therapeutic efifcacy.     

A new endoscopic ultrasonography image processing method to evaluate the prognosis for pancreatic cancer treated with interstitial brachytherapy

AIM:To develop a fuzzy classification method to score the texture features of pancreatic cancer in endoscopic ultrasonography(EUS)images and evaluate its utility in making prognosis judgments for patients with unresectable pancreatic cancer treated by EUS-guided interstitial brachytherapy.METHODS:EUS images from our retrospective database were analyzed.The regions of interest were drawn,and texture features were extracted,selected,and scored with a fuzzy classification method using a C++program.Then,patients with unresectable pancreatic cancer were enrolled to receive EUS-guided iodine 125 radioactive seed implantation.Their fuzzy classification scores,tumor volumes,and carbohydrate antigen 199(CA199)levels before and after the brachytherapy were recorded.The association between the changes in these parameters and overall survival was analyzed statistically.RESULTS:EUS images of 153 patients with pancreatic cancer and 63 non-cancer patients were analyzed.A total of 25 consecutive patients were enrolled,and they tolerated the brachytherapy well without any complications.There was a correlation between the change in the fuzzy classification score and overall survival(Spearman test,r=0.616,P=0.001),whereas no correlation was found to be significant between the change in tumor volume(P=0.663),CA199 level(P=0.659),and overall survival.There were 15 patients with a decrease in their fuzzy classification score after brachytherapy,whereas the fuzzy classification score increased in another 10 patients.There was a significant difference in overall survival between the two groups(67 d vs 151 d,P=0.001),but not in the change of tumor volume and CA199 level.CONCLUSION:Using the fuzzy classification method to analyze EUS images of pancreatic cancer is feasible,and the method can be used to make prognosis judgments for patients with unresectable pancreatic cancer treated by interstitial brachytherapy.     

Treatment outcomes of chemotherapy between unresectable and recurrent biliary tract cancer

AIM: To evaluate the differences in the treatment outcomes between the unresectable and recurrent biliary tract cancer patients who received chemotherapy.METHODS: Patients who were treated with gemcitabine and S-1 combination therapy in the previous prospective studies were divided into groups of unresectable and recurrent cases. The tumor response, time-to-progression, overall survival, toxicity, and dose intensity were compared between these two groups.RESULTS: Response rate of the recurrent group was higher than that of the unresectable group (40.0% vs 25.5%; P = 0.34). Median time-to-progression of the recurrent and unresectable groups were 8.7 mo (95%CI), 1.2 mo, not reached) and 5.7 mo (95%CI: 4.0-7.0 mo), respectively (P = 0.14). Median overall survival of the recurrent and the unresectable groups were 16.1 mo (95%CI: 2.0 mo-not reached) and 9.6 mo (95%CI: 7.1-11.7 mo), respectively (P = 0.10). Dose intensities were significantly lower in the recurrent groups (gemcitabine: recurrent group 83.5% vs unresectable group 96.8%; P < 0.01, S-1: Recurrent group 75.9% vs unresectable group 91.8%; P < 0.01). Neutropenia occurred more frequently in recurrent group (recurrent group 90% vs unresectable group 55%; P = 0.04).CONCLUSION: Not only the efficacy but also the toxicity and dose intensity were significantly different between unresectable and recurrent biliary tract cancer.     

Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

AIM:To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma(HCC)in patients with established cirrhosis.METHODS:From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled.According to the Barcelona Clinic Liver Cancer(BCLC)classification,patients were in the advanced stage(BCLC-C)or in the intermediate stage(BCLC-B)but unfit or unresponsive to other therapeutic strategies.Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo,and analyzed according to the modified Response Evaluation Criteria in Solid Tumors.Sorafenib was administered at 800 mg/d,until radiological progression or occurrence of unacceptable adverse events(AEs).Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.RESULTS:Forty-four patients were enrolled,15 had intermediate HCC and 14 a Child-Pugh score of B7.AEs caused treatment interruption in 19 patients(43%),and median treatment duration was shorter in this subset(5 wk vs 19 wk,P<0.001)and in the BCLC-C subgroup(13 wk vs 40 wk,P=0.015).No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years.After 16 wk of treatment,18 patients(41%)had stable disease or partial response.Patients with viral infection or BCLC-C were at higher risk of disease progression.ECOG,extrahepatic spread,macrovascular invasion,alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.CONCLUSION:In patients with cirrhosis and HCC treated with sorafenib,AEs are a common cause of early treatment withdrawal.Vascular invasion and extrahepatic spread condition early response to treatment and survival.Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter overall survival.     

Transarterial chemoembolization in combination with percutaneous ablation therapy in unresectable hepatocellular carcinoma: a meta‐analysis

Background: Recent evidence suggests that transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) or a percutaneous ethanol injection (PEI) may have a synergistic effect in treating hepatocellular carcinoma (HCC). The aim of the current meta‐analysis was to identify the survival benefits of TACE combined with percutaneous ablation (PA) therapy (RFA or PEI) for unresectable HCC compared with those of TACE or PA alone. Methods: Randomized‐controlled trials (RCTs) published as full papers or abstracts were searched to assess the survival benefit or tumour recurrence for patients with unresectable HCC on electronic databases. The primary outcome was survival. The secondary outcomes were response to therapy and tumour recurrence. Results: Ten RCTs met the criteria to perform a meta‐analysis including 595 participants. TACE combined with PA therapy, respectively improved, 1‐, 2‐, and 3‐year overall survival compared with that of monotherapy [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.14–4.57; P=0.020], (OR=4.53, 95% CI 2.62–7.82, P<0.00001) and (OR=3.50, 95% CI 1.75–7.02, P=0.0004). Sensitivity analysis demonstrated a significant benefit in 1‐, 2‐ and 3‐year overall survival of TACE plus PEI compared with that of TACE alone for patients with large HCC lesions, but not in TACE plus RFA vs RFA for patients with small HCCs. The pooled result of five RCTs showed that combination therapy decreased tumour recurrence compared with that of monotherapy (OR=0.45, 95% CI 0.26–0.78, P=0.004). Conclusion: TACE combined with PA therapy especially PEI improved the overall survival status for large HCCs.     

Clinical outcome of small hepatocellular carcinoma after different treatments:A meta-analysis

AIM:To compare clinical outcomes between surgical resection(RES)and nonsurgical-RES(nRES)ablation therapies for small hepatocellular carcinoma(HCC).METHODS:MEDLINE,Embase and Cochrane Library databases were systematically searched for studies of RES and nRES treatments for small HCC between January 2003 and October 2013.The clinical outcome measures evaluated included overall survival rate,disease-free survival rate,adverse events,and local recurrence rate.Odds ratios(ORs)with 95%CIs were calculated using either the fixed effects model or random effects model.Theχ2 and I2 tests were calculated to assess the heterogeneity of the data.Funnel plots were used to assess the risk of publication bias.RESULTS:Our analysis included 12 studies that consisted of a total of 1952 patients(RES vs nRES),five studies that consisted of 701 patients[radiofrequency ablation(RFA)vs percutaneous ethanol injection(PEI)],and five additional studies[RFA vs RFA+transcatheter arterial chemoembolization(TACE)]that all addressed the treatment of small HCC.For cases of RES vs nRES,there was no significant difference in the 1-year(OR=0.99,95%CI:0.87-1.12,P=0.85)or 3-year(OR=0.97,95%CI:0.84-1.11,P=0.98)overall survival rate;however,there was a significant increase in the RES group in the 5-year overall survival rate(OR=0.81,95%CI:0.68-0.95,P=0.01).The 1-year(OR=0.94,95%CI:0.82-1.08,P=0.37)and 5-year(OR=0.99,95%CI:0.85-1.14,P=0.85)disease-free survival rates showed no significant differences between the two groups.The3-year disease-free survival rate(OR=0.81,95%CI:0.69-0.96;P=0.02)was higher in the RES group.For cases of RFA vs PEI,our data analysis indicated that RFA treatment was associated with significantly higher2-year(OR=0.76,95%CI:0.58-0.99,P=0.043)and3-year(OR=0.73,95%CI:0.54-0.98,P=0.039)overall survival rates;however,there were no significant differences in the 1-year(OR=0.92,95%CI:0.72-1.17,P=0.0502)overall survival rate or incidence of adverse events(OR=1.84,95%CI:0.76-4.45,P=0.173).For cases of RFA vs RFA+TACE,there were no significant differences in the 1-year(OR=1.17,95%CI:0.88-1.56,P=0.27)or 3-year(OR=1.25,95%CI:0.90-1.73,P=0.183)overall survival rate;however,the 5-year overall survival rate(OR=3.19,95%CI:1.51-6.74,P=0.002)in patients treated by RFA+TACE was higher than that treated by RFA alone.CONCLUSION:Surgical resection is superior to nonsurgical ablation for the treatment of small HCC.Among the studies analyzed,RFA is the most efficacious single nonsurgical ablation treatment.     

Overexpression of lysine specific demethylase 1 predicts worse prognosis in primary hepatocellular carcinoma patients

AIM: To investigate the clinicopathological features and prognostic value of lysine specific demethylase 1 (LSD1) in hepatocellular carcinoma (HCC).METHODS: We examined LSD1 expression in 60 paired liver cancer tissues and adjacent noncancerous tissues by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting. In addition, we analyzed LSD1 expression in 198 HCC samples by immunohistochemistry. The relationship between LSD1 expression, clinicopathological features and patient survival was investigated.RESULTS: Immunohistochemistry, Western blotting, and qRT-PCR consistently confirmed LSD1 overexpression in HCC tissues compared to adjacent non-neoplastic tissues (P < 0.01). Additionally, immunostaining showed more LSD1-positive cells in the higher tumor stage (T3-4) and tumor grade (G3) than in the lower tumor stage (T1-2, P < 0.001) and tumor grade (G1-2, P < 0.001), respectively. Moreover, HCC patients with high LSD1 expression had significantly lower 5-year overall survival rates (P < 0.001) and lower 5-year disease-free survival rates (P < 0.001), respectively. A Cox proportional hazards model further demonstrated that LSD1 over-expression was an independent predictor of poor prognosis for both 5-year disease-free survival [hazards ratio (HR) = 1.426, 95%CI: 0.672-2.146, P < 0.001] and 5-year overall survival (HR = 2.456, 95%CI: 1.234-3.932, P < 0.001) in HCC.CONCLUSION: Our data suggest for the first time that the overexpression of LSD1 protein in HCC tissues indicates tumor progression and predicts poor prognosis.     

Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non‐resectable hepatocellular carcinoma tumours of ≥3 cm

Objectives

The optimal locoregional treatment for non-resectable hepatocellular carcinoma (HCC) of ≥3 cm in diameter is unclear. Transarterial chemoembolization (TACE) is the initial intervention most commonly performed, but it rarely eradicates HCC. The purpose of this study was to measure survival in HCC patients treated with adjuvant stereotactic body radiotherapy (SBRT) following TACE.

Methods

A retrospective study of patients with HCC of ≥3 cm was conducted. Outcomes in patients treated with TACE alone (n = 124) were compared with outcomes in those treated with TACE + SBRT (n = 37).

Results

There were no significant baseline differences between the two groups. The pre-TACE mean number of tumours (P = 0.57), largest tumour size (P = 0.09) and total tumour diameter (P = 0.21) did not differ significantly between the groups. Necrosis of the HCC tumour, measured after the first TACE, did not differ between the groups (P = 0.69). Local recurrence was significantly decreased in the TACE + SBRT group (10.8%) in comparison with the TACE-only group (25.8%) (P = 0.04). After censoring for liver transplantation, overall survival was found to be significantly increased in the TACE + SBRT group compared with the TACE-only group (33 months and 20 months, respectively; P = 0.02).

Conclusions

This retrospective study suggests that in patients with HCC tumours of ≥3 cm, treatment with TACE + SBRT provides a survival advantage over treatment with only TACE. Confirmation of this observation requires that the concept be tested in a prospective, randomized clinical trial.     

Outcomes after curative treatment for cryptogenic cirrhosis-associated hepatocellular carcinoma satisfying the Milan criteria

Background and Aim: The prognosis of cryptogenic cirrhosis‐associated hepatocellular carcinoma (CC‐HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC‐HCC. Methods: Consecutive 36 curatively treated CC‐HCC patients satisfying the Milan Criteria were compared with corresponding 211 HCV‐associated HCC (HCV‐HCC) patients. The clinical background, tumor recurrence rate, overall survival rate, and prognostic values of the patients were assessed. Results: The size of CC‐HCCs was larger than that of HCV‐HCCs (P = 0.01). The respective tumor recurrence rates at 1, 3, and 5 years were 11%, 32%, and 46% in the CC‐HCC, and 21%, 59%, and 81% in the HCV‐HCC. The respective overall survival rates at 1, 3, and 5 years were 94%, 85%, and 80% in the CC‐HCC, and 98%, 81%, and 61% in the HCV‐HCC. CC‐HCC patients had a lower tumor recurrence rate and a higher survival rate compared to the HCV‐HCC patients (P = 0.001 and P = 0.02, respectively). Via multivariate analysis, significant factors for high recurrence rate were number of HCCs (P = 0.02) and serum alpha fetoprotein levels (P = 0.03) in CC‐HCC, whereas multiple tumors (P < 0.001), large tumor size (P = 0.01), and high alanine aminotransferase (P = 0.04) in HCV‐HCC. The factor for survival was albumin in both groups. Conclusion: The size of CC‐HCC was larger than that of HCV‐HCC even in patients who received curative treatment; however, the risk for recurrence and the mortality of the patients with CC‐HCC was lower than those with HCV‐HCC.     

Short- and long-term outcomes of hepatectomy combined with intraoperative radiofrequency ablation for patients with multiple primarily unresectable colorectal liver metastases: a propensity matching analysis

BackgroundHepatectomy combined with intraoperative radiofrequency ablation (IORFA) is a strategy to eliminate all tumors in patients with multiple colorectal liver metastases (CRLM). This study aimed to evaluate the surgical and oncological outcomes of hepatectomy + IORFA for multiple unresectable CRLM.MethodsWe included patients who underwent combined hepatectomy and IORFA for multiple unresectable CRLM (n = 67) or hepatectomy alone (n = 268) for CRLM. Patients were matched in a 1:1 propensity score analysis to compare the short- and long-term outcomes between groups.ResultsPatients in hepatectomy + IORFA group had a median number of 10 liver lesions. Postoperative morbidity and the rate of major complications was similar between groups (P = 0.362, P = 1.000). The median overall survival (OS), progression free survival (PFS) and hepatic recurrence free survival (HRFS) was similar between groups (3-year OS: 54.2% versus 60.9%, P = 0.389; 3-year PFS: 7.9% versus 19.6%, P = 0.148; 3-year HRFS: 16.7% versus 31.5%, P = 0.202). Re-hepatectomy or radiofrequency ablation was used to treat 47.5% of hepatic recurrences, and the median OS was significantly higher than for patients treated with systemic treatment alone (P < 0.001).ConclusionsCombining hepatectomy and IORFA could provide comparable survival rates for patients with multiple unresectable CRLM compared to those with resectable CRLM treated with hepatectomy alone.