Combination of TACE and Sorafenib Improves Outcomes in BCLC Stages B/C of Hepatocellular Carcinoma: A Single Centre Experience

Background & Aim. Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C.Material and methods. We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival.Results. Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLC-C. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted.Conclusion. TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.     

Determinants of survival following hepatocellular carcinoma in Egyptian patients with untreated chronic HCV infection in the pre-DAA era

Background and Study Aims

In this study we assessed rates and determinants of survival in people with untreated chronic HCV infection and hepatocellular carcinoma (HCC) in an Egyptian liver clinic setting.

Comparison of hepatic resection and transarterial chemoembolization for solitary hepatocellular carcinoma

AIM: To compare the outcomes of hepatic resection and transarterial chemoembolization (TACE) for solitary hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer (BCLC) staging system.METHODS: A consecutive sample of 540 patients with solitary HCC who underwent liver resection (n = 312) or TACE (n = 128) were included in the present study. Baseline characteristics, tumor characteristics, and post-operative complications were compared between the two groups. The Kaplan-Meier method was used for long-term survival analysis. Independent prognostic predictors were identified using the Cox proportional hazards model (univariate and multivariate analyses).RESULTS: The TACE and liver resection groups had similar baseline demographic and clinicopathological characteristics. The TACE group showed a significantly lower rate of major complications than the liver resection group (3.9% vs 17.4%, P < 0.001). Univariate and multivariate analyses indicated that TACE did not contribute to poor overall survival compared with liver resection; however, a solitary tumor diameter of greater than 6 cm should be considered a risk factor for poor overall survival (HR = 1.328, 95%CI: 1.002-1.783, P = 0.048). The liver resection and TACE groups had comparable overall survival rates at 1 year, 3 years, and 5 years (86.2%, 62.8%, and 44.0% vs 88.3%, 59.8%, and 40.6%, respectively, P = 0.419). In cases with tumor diameters equal to or less than 6 cm, the liver resection group showed a survival benefit compared with the TACE group at 1 year, 3 years, and 5 years (P = 0.030). The 1-, 3-, and 5-year overall survival rates of HCC cases with tumor diameters of more than 6 cm were similar among the liver resection and TACE groups (P = 0.467).CONCLUSION: A tumor diameter of 6 cm should be the cutoff for deciding between liver resection and TACE.     

Risk factors and surgical outcomes for spontaneous rupture of BCLC stages A and B hepatocellular carcinoma: A case-control study

AIM: To investigate the risk factors and surgical outcomes for spontaneous rupture of Barcelona Clinic Liver Cancer (BCLC) stages A and B hepatocellular carcinoma (HCC).METHODS: From April 2002 to November 2006, 92 consecutive patients with spontaneous rupture of BCLC stage A or B HCC undergoing hepatic resection were included in a case group. A control arm of 184 cases (1:2 ratio) was chosen by matching the age, sex, BCLC stage and time of admission among the 2904 consecutive patients with non-ruptured HCC undergoing hepatic resection. Histological confirmation of HCC was available for all patients and ruptured HCC was confirmed by focal discontinuity of the tumor with surrounding perihepatic hematoma observed intraoperatively. Patients with microvascular thrombus in the hepatic vein branches were excluded from the study. Clinical data and survival time were collected and analysed.RESULTS: Sixteen patients were excluded from the study based on exclusion criteria, of whom 3 were in the case group and 13 in the control group. Compared with the control group, more patients in the case group had underlying diseases of hypertension (10.1% vs 3.5%, P = 0.030) and liver cirrhosis (82.0% vs 57.9%, P < 0.001). Tumors in 67 (75.3%) patients in the case group were located in segments II, III and VI, and the figure in the control group was also 67 (39.7%) (P < 0.001). On multivariate analysis, hypertension (HR = 7.38, 95%CI: 1.91-28.58, P = 0.004), liver cirrhosis (HR = 6.04, 95%CI: 2.83-12.88, P < 0.001) and tumor location in segments II, III and VI (HR = 5.03, 95%CI: 2.70-6.37, P < 0.001) were predictive for spontaneous rupture of HCC. In the case group, the median survival time and median disease-free survival time were 12 mo (range: 1-78 mo) and 4 mo (range: 0-78 mo), respectively. The 1-, 3- and 5-year overall survival rates and disease-free survival rates were 66.3%, 23.4% and 10.1%, and 57.0%, 16.8% and 4.5%, respectively. Only radical resection remained predictive for overall survival (HR = 0.32, 95%CI: 0.08-0.61, P = 0.015) and disease-free survival (HR = 0.12, 95%CI: 0.01-0.73, P = 0.002).CONCLUSION: Tumor location, hypertension and liver cirrhosis are associated with spontaneous rupture of HCC. One-stage hepatectomy should be recommended to patients with BCLC stages A and B disease.     

Intermediate-advanced hepatocellular carcinoma in Argentina:Treatment and survival analysis

BACKGROUND Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.AIM To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic options.METHODS This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC) HCC stages(BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death.Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios(HR) calculations and 95% confidence intervals(95%CI).RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D.Corresponding median survival were 15 mo(IQR 5-26 mo), 5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P 0.0001), respectively. Among BCLC-B patients(n =135), 57% received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR =0.29(CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival [HR = 0.15(CI: 0.04-0.56, P = 0.005)]. Eighty-two patients were treated with sorafenib, mostly BCLC-B and C(87.8%). However,12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo); which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26(CI: 0.09-0.71); P= 0.013].CONCLUSION In this real setting, our results were lower than expected. This highlights unmet needs in Argentina, prior to the introduction of new treatments for HCC.     

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 in hepatocellular carcinoma treatment: Barcelona clinic liver cancer staging system

Hepatocellular carcinoma(HCC),the fifth most common cancer that predominantly occurs in liver cirrhosis patients,requires staging systems to design treatments. The barcelona clinic liver cancer staging system(BCLC) is the most commonly used HCC management guideline. For BCLC stage B(intermediate HCC),transarterial chemoembolization(TACE) is the standard treatment. Many studies support the use of TACE in early and advanced HCC patients. For BCLC stage 0(very early HCC),TACE could be an alternative for patients unsuitable for radiofrequency ablation(RFA) or hepatic resection. In patients with BCLC stage A,TACE plus RFA provides better local tumor control than RFA alone. TACE can serve as bridge therapy for patients awaiting liver transplantation. For patients with BCLC B,TACE provides survival benefits compared with supportive care options. However,because of the substantial heterogeneity in the patient population with this stage,a better patient stratification system is needed to select the best candidates for TACE. Sorafenib represents the first line treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a demonstrable effect in delaying tumor progression. Additionally,TACE plus radiotherapy has yielded better survival in patients with HCC and portal venous thrombosis. Considering these observations together,TACE clearly has a critical role in the treatment of HCC as a stand-alone or combination therapy in each stage of HCC. Diverse treatment modalities should be used for patients with HCC and a better patient stratification system should be developed to select the best candidates for TACE.     

Sorafenib after resection improves the outcome of BCLC stage C hepatocellular carcinoma

AIM: To evaluate whether sorafenib use after resection impacts tumor relapse and survival in Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).METHODS: This retrospective study enrolled 36 male BCLC stage C HCC patients with portal vein thrombus and Child-Pugh class A liver function. Twenty-four patients received only surgical resection (SR), and 12 patients received oral sorafenib within 30 d after surgery. The primary outcomes were time to progression (TTP) (the time from surgical resection until HCC recurrence or extrahepatic metastases) and overall survival (OS). The secondary outcome was the rate of postoperative recurrence or metastasis. TTP and OS were analyzed using Kaplan Meier curves.RESULTS: There were no significant differences between the two groups in the serum levels of alpha-fetoprotein, copies of hepatitis B virus-DNA, preoperative laboratory results, degree of hepatic fibrosis, types of portal vein tumor thrombus, number of satellite lesions, tumor diameter, pathological results, volume of blood loss, volume of blood transfusion, or surgery time (all P > 0.05). Patients in the SR + sorafenib group had a significantly longer TTP (29 mo vs 22 mo, P = 0.041) and a significantly longer median OS (37 mo vs 30 mo, P = 0.01) compared to patients in the SR group. The SR group had 18 cases (75%) of recurrence/metastasis while the SR + sorafenib group had six cases (50%) of recurrence/metastasis. A total of 19 patients died after surgery (five in the SR + sorafenib group and 14 in the SR group). The most common sorafenib-related adverse events were skin reactions, diarrhea, and hypertension, all of which were resolved with treatment.CONCLUSION: Sorafenib after SR was well-tolerated. Patients who received sorafenib after SR had better outcomes compared to patients who received only SR.     

Transarterial chemoembolization plus sorafenib versus sorafenib for intermediate–advanced hepatocellular carcinoma: A meta-analysis comparing clinical outcomes

Background:Hepatocellular carcinoma (HCC) ranks as the sixth most common cancer and the second leading cause of cancer-related death worldwide, local and systemic therapies are beneficial for those who have more advanced disease or are not suitable for radical treatment. We aim to investigate the clinical outcomes of transarterial chemoembolization (TACE) plus sorafenib compared with sorafenib monotherapy for intermediate–advanced HCC.Methods:A systematic search according to preferred reporting items for systematic reviews and meta-analyses guidelines in the PubMed database was conducted from inception to December 31, 2020 for published studies comparing survival outcomes and tumor response between TACE + sorafenib and sorafenib alone for intermediate–advanced HCC.Results:Five eligible cohort studies and a randomized controlled trial with a total of 3015 patients were identified. We found that the TACE + sorafenib group had a significantly better overall survival (OS) (hazard ratio, 0.77; 95% confidence interval [CI] 0.66–0.88, P < .001) than those treated with sorafenib. Median OS ranged from 7.0 to 22.0 months with TACE + sorafenib and from 5.9 to 18.0 months with sorafenib. The combination of TACE + sorafenib had a significantly better time to progression (hazard ratio, 0.74; 95% CI 0.65–0.82, P < .001) than those treated with sorafenib. Median time to progression ranged from 2.5 to 5.3 months with TACE + sorafenib and from 2.1 to 2.8 months with sorafenib. The results showed the TACE + sorafenib group had a higher disease control rate (log odds ratio, 0.52; 95% CI 0.25–0.80, P = .0002), objective response rate (log odds ratio, 0.85; 95% CI 0.37–1.33, P = .0006) than sorafenib group. Hand–foot skin reaction, diarrhea, fatigue, vomiting, and alanine aminotransferase (ALT) elevation were common adverse events. The adverse events were similar between the 2 groups excluding elevated ALT.Conclusion:Although the TACE + sorafenib group had a higher elevated ALT, the combination of TACE + sorafenib had an OS benefit compared with sorafenib in the treatment of intermediate–advanced HCC. Further research is necessary to affirm this finding and clarify whether certain subgroups benefit from different combinations between TACE and sorafenib.     

Prognostic factors for survival after transarterial chemoembolization combined with microwave ablation for hepatocellular carcinoma

AIM: To analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with microwave ablation (MWA) for hepatocellular carcinoma (HCC).METHODS: Clinical data of 86 patients who underwent TACE combined with MWA between January 2006 and December 2013 were retrospectively analyzed in this study. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 13 prognostic factors affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant.RESULTS: Median follow-up time was 47.6 mo, and median survival time of enrolled patients was 21.5 mo. The 1-, 2-, 3- and 5-year overall survival rates were 72.1%, 44.1%, 31.4% and 13.9%, respectively. Tumor size(χ² = 14.999, P = 0.000), Barcelona Clinic Liver Cancer (BCLC) stage (χ² = 29.765, P = 0.000), Child-Pugh class (χ² = 51.820, P = 0.000), portal vein tumor thrombus (PVTT) (χ² = 43.086, P = 0.000), arterio-venous fistula (χ² = 29.791, P = 0.000), MWA therapy times (χ² = 12.920, P = 0.002), Eastern Cooperative Oncology Group (ECOG) score (χ² = 28.660, P = 0.000) and targeted drug usage (χ² = 10.901, P = 0.001) were found to be significantly associated with overall survival by univariate analysis. Multivariate analysis identified that tumor size (95%CI: 1.608-4.962, P = 0.000), BCLC stage (95%CI: 1.016-2.208, P = 0.020), PVTT (95%CI: 2.062-9.068, P = 0.000), MWA therapy times (95%CI: 0.402-0.745, P = 0.000), ECOG score (95%CI: 1.012-3.053, P = 0.045) and targeted drug usage (95%CI: 1.335-3.143, P = 0.001) were independent prognostic factors associated with overall survival.CONCLUSION: Superior performance status, MWA treatment and targeted drug were favorable factors, and large HCC, PVTT and advanced BCLC stage were risk factors for survival after TACE-MWA for HCC.     

3D conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

AIM:To compare transcatheter arterial chemoembolization(TACE)and 3D conformal radiotherapy(3D-CRT)with TACE monotherapy in hepatocellular carcinoma(HCC).METHODS:We searched all the eligible studies from the Cochrane Library,Pub Med,Medline,Embase,and CNKI.The meta-analysis was performed to assess the survival benefit,tumor response,and the decline inα-fetoprotein(AFP)level.According to the heterogeneity of the studies,pooled OR with 95%CI were calculated using the fixed-effects or random-effects model.An observed OR>1 indicated that the addition of 3D-CRT to TACE offered survival benefits to patients that could be considered statistically significant.Statistical analyses were performed using Review Manager Software.RESULTS:Ten studies met the criteria to perform a meta-analysis including 908 HCC participants,with 400patients in the TACE/3D-CRT combination group and508 in the TACE alone group.TACE combined with 3DCRT significantly improved 1-,2-and 3-year overall survival compared with TACE monotherapy(OR=1.87,95%CI:1.37-2.55,P<0.0001),(OR=2.38,95%CI:1.78-3.17,P<0.00001)and(OR=2.97,95%CI:2.10-4.21,P<0.00001).In addition,TACE plus 3DCRT was associated with a higher tumor response(complete remission and partial remission)(OR=3.81;95%CI:2.70-5.37;P<0.00001),and decline rates of AFP level(OR=3.24,95%CI:2.09-5.02,P<0.00001).CONCLUSION:This meta-analysis demonstrated that TACE combined with 3D-CRT was better than TACE monotherapy for patients with HCC,which needs to be confirmed by large multicenter trials.     

Postoperative adjuvant sorafenib improves survival outcomes in hepatocellular carcinoma patients with microvascular invasion after R0 liver resection: a propensity score matching analysis

BackgroundMicrovascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR).MethodsThe data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed.Results728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease.ConclusionsPA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.     

Clinical outcome of 251 patients with extrahepatic metastasis at initial diagnosis of hepatocellular carcinoma: Does transarterial chemoembolization improve survival in these patients?

Background and Aims: The therapeutic efficacy of transarterial chemoembolization (TACE) has not been evaluated in hepatocellular carcinoma (HCC) patients with extrahepatic metastasis. We investigated the efficacy of TACE with/without systemic chemotherapy (s‐chemo) in these patients. Methods: We performed a survival analysis of consecutive HCC patients with extrahepatic metastasis, diagnosed at initial presentation according to treatment modality after stratification, using the Child–Pugh classification and intrahepatic HCC T stage, retrospectively. Results: Between 2005 and 2007, 251 patients were newly diagnosed with HCC involving extrahepatic metastasis at our institution. Among those, 226 were classified as Child–Pugh A–B and the other 25, Child‐Pugh C. Within the Child–Pugh A–B group, repeated TACE or transarterial chemoinfusion (TACI) was performed with/without s‐chemo in 171 patients. Eight of 226 received s‐chemo alone, and 47, conservative management (CM) alone. The median survival time of patients treated with TACE/TACI with s‐chemo, TACE/TACI alone, and CM was 10, 5, and 2.9 months in patients classified as Child–Pugh A and T3‐stage HCC (TACE/TACI with s‐chemo vs CM, P = 0.0354; TACE/TACI alone vs CM, P = 0.0553) and 7.1, 2.6, and 1.6 months in Child–Pugh B and T3‐stage patients, respectively (TACE/TACI with s‐chemo vs CM, P = 0.0097; TACE/TACI alone vs CM, P < 0.0001). Individual treatment with TACE/TACI or sorafenib showed independent prognostic significance in the multivariate analysis. Conclusion: Repeated TACE could show significant survival benefits in metastatic HCC patients with conserved liver function and intrahepatic HCC T3 stage. The survival data of our study could be used as a historical control for TACE monotherapy in future clinical trials evaluating combination treatments containing TACE in these patients.     

Transarterial chemoembolization in Barcelona Clinic Liver Cancer Stage 0/A hepatocellular carcinoma

AIM:To evaluate the clinical characteristics of patients with Barcelona Clinic Liver Cancer(BCLC)stage 0 and A hepatocellular carcinoma(HCC)after transarterial chemoembolization(TACE).METHODS:Between January 2001 and September2011,129 patients with BCLC stage 0 and stage A HCC who underwent TACE were retrospectively enrolled.Patient characteristics,routine computed tomography and TACE findings,survival time and 1-,5-,and 10-year survival rates,risk factors for mortality,and survival rates according to the number of risk factors were assessed.RESULTS:The mean size of HCC tumors was 2.4±1.1 cm,and the mean number of TACE procedures performed was 2.5±2.1.The mean overall survival time and 1-,5-,and 10-year survival rates were 80.6±4.9 mo and 91%,63%and 49%,respectively.In the Cox regression analysis,a Child-Pugh score>5(P=0.005,OR=3.86),presence of arterio-venous shunt(P=0.032,OR=4.41),amount of lipiodol used(>7 mL;P=0.013,OR=3.51),and female gender(P=0.008,OR=3.47)were risk factors for mortality.The 1-,5-,and 10-year survival rates according to the number of risk factors present were 96%,87%and 87%(no risk factors),89%,65%,and 35%(1 risk factor),96%,48%and unavailable(2 risk factors),and 63%,17%,and 0%(3 risk factors),respectively(P<0.001).CONCLUSION:TACE may be used as curative-intent therapy in patients with BCLC stage 0 and stage A HCC.The Child-Pugh score,arterio-venous shunt,amount of lipiodol used,and gender were related to mortality after TACE.     

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.     

Is laparoscopic liver resection suitable for selected patients with BCLC stage B HCC? A propensity score-matched analysis

BackgroundThe optimal treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is controversial given the variability of tumour status within this group of patients. This aim of this study was to compare the outcomes of laparoscopic liver resection (LLR) to transarterial chemoembolization (TACE) in a subset of selected patients with BCLC stage B HCC.MethodsPatients with resectable BCLC stage B HCC who underwent treatment between April 2015 and October 2018 were identified for further analysis. Propensity score matching (PSM) was conducted to minimize effect of confounding factors. Perioperative and long-term outcomes were compared between the two groups and multivariate analysis was performed to identify risk factors related to the overall survival (OS).ResultsFrom a total of 224 patients 70 were included into each group after PSM. The overall and major morbidity were comparable between the LLR and TACE groups (P = 0.700 and P = 0.500 after PSM, respectively). The OS in LLR group was significantly better than that in the TACE group (P < 0.001). Tumor number ≥4, the diameter of the biggest tumor >5 cm, and patients who underwent TACE were independent predictors of poorer OS.ConclusionsLLR for selected patients with BCLC stage B HCC is safe and feasible and has improved survival as compared to TACE.     

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging

AIM: To assess how ascites and alpha-fetoprotein(AFP) added to the Barcelona Clinic Liver Cancer(BCLC) staging predict hepatocellular carcinoma survival.METHODS: The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh(CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data(including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed.RESULTS:At the time the data were censored,123/496(24.8%)and 218/564(38.6%)patients with BCLC stages A and B,respectively,had died.Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo[95%confidence interval(95%CI):29.7-32.3]and 22.7mo(95%CI:20.7-24.8),respectively.The presenceof ascites,multiple focal lesions,large tumor size,AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis(P0.001).Among stage A patients,18%had ascites,33%had AFP≥200 ng/m L,and 8%had both.Their median survival in the presence of ascites was shorter if AFP was≥200 ng/m L(19 mo vs 24 mo),and in the absence of ascites,patients with AFP≥200 ng/m L had a shorter survival(28mo vs 39 mo).For stage B patients,survival for the corresponding groups was 12,18,19 and 22 mo.The one-,two-,and three-year survival rates for stage A patients without ascites and AFP200 ng/m L were94%,77%,and 71%,respectively,and for patients with ascites and AFP≥200 ng/m L were 83%,24%,and 22%,respectively(P0.001).Adding ascites and AFP≥200 ng/m L improved the discriminatory ability for predicting prognosis(area under the curve,0.618vs 0.579 for BCLC,P0.001).CONCLUSION:Adding AFP and ascites to the BCLC staging classification can improve prognosis prediction for early and intermediate stages of hepatocellular carcinoma.     

Liver resection for intermediate hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer(BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization(TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC.     

Survival rates according to barcelona clinic liver cancer sub-staging system after transarterial embolization for intermediate hepatocellular carcinoma

AIM: To investigate the survival rates after transarterial embolization(TAE).METHODS: One hundred third six hepatocellular carcinoma(HCC) patients [90 barcelona clinic liver cancer(BCLC) B] were submitted to TAE between August 2008 and December 2013 in a single center were retrospectively studied. TAE was performed via superselective catheterization followed by embolization with polyvinyl alcohol or microspheres. The date of the first embolization until death or the last follow-up date was used for the assessment of survival. The survival rates were calculated using the Kaplan-Meier method, and the groups were compared using the log-rank test.RESULTS: The overall mean survival was 35.8 mo(95%CI: 25.1-52.0). The survival rates of the BCLC A patients(33.7%) were 98.9%, 79.0% and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo(95%CI: 27.5-52.0). The survival rates of the BCLC B patients(66.2%) were 89.0%, 69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0 mo(95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging showed significant differences between the groups, with mean survival rates in the B1, B2, B3 and B4 groups of 33.5 mo(95%CI: 32.8-34.3), 28.6 mo(95%CI: 27.5-29.8), 19.0 mo(95%CI: 17.2-20.9) and 13 mo, respectively(P = 0.013).CONCLUSION : The BCLC sub-stagingsystem could add additional prognosis information for postembolization survival rates in HCC patients.     

Prognostic factors for survival in patients with unresectable hepatocellular carcinoma undergoing chemoembolization with doxorubicin drug-eluting beads: a preliminary study

Background:

Transarterial chemoembolization (TACE) with drug-eluting beads (DEB) is a new treatment modality. Little is known about prognostic factors affecting survival after DEB TACE for patients with hepatocellular carcinoma (HCC).

Methods:

Patients who underwent TACE with doxorubicin DEB for unresectable HCC during 2006–2008 were studied. Survival was calculated from the day of first transcatheter therapy. Survival analysis was performed using Kaplan–Meier estimations. Survival curves were compared using the log-rank test.

Results:

Fifty patients underwent chemoembolization with doxorubicin DEB. They included 39 women and 11 men, with a median age of 57.5 years (range 28–91 years). Eighteen patients died during the study period and 32 remained alive. Overall survival rates at 6 months, 1 year and 2 years from the first administration of doxorubicin DEB TACE were 71%, 65% and 51%, respectively. Prognostic factors found to be significant on univariate analysis were Child–Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3.0 g/dl, Model for End-stage Liver Disease (MELD) score, serum alphafetoprotein (AFP), Cancer of the Liver Italian Programme (CLIP) score, tumour satisfying Milan criteria, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and Barcelona Clinic Liver Cancer (BCLC) staging.

Conclusions:

Child–Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3 g/dl, MELD score, serum AFP, CLIP score, Milan criteria, ECOG PS and BCLC staging were found to be prognostic markers of survival after treatment with doxorubicin DEB TACE in patients with unresectable HCC.