A prediction model for liver abscess developing after transarterial chemoembolization in patients with hepatocellular carcinoma

BackgroundLiver abscess is a rare but potentially fatal complication of transarterial chemoembolization. Other than for biliary abnormalities, risk factors for liver abscess formation after transarterial chemoembolization have rarely been discussed.AimsTo identify other risk factors of liver abscess after transarterial chemoembolization in patients with hepatocellular carcinoma.MethodsData for 5299 patients with hepatocellular carcinoma who underwent transarterial chemoembolization from July 1999 to December 2009 were retrospectively reviewed. 72 patients who experienced liver abscess after transarterial chemoembolization were enrolled as a case group, which was compared with a randomly selected control group (n = 1009) of patients who did not develop liver abscess after transarterial chemoembolization.ResultsPneumobilia, type 2 biliary abnormality, type 1 biliary abnormality, diabetes mellitus, tumour number (≥3), tumour size (≥3 cm), and tumour necrosis on the pre-transarterial chemoembolization computed tomography, and gelfoam embolization and vessel injury during transarterial chemoembolization were all significant predisposing factors for liver abscess after transarterial chemoembolization. A prediction model for postembolization liver abscess was developed from these risk factors.ConclusionThe group of patients with risk scores greater than 71 showed a significantly increased risk of liver abscess after transarterial chemoembolization. These high-risk patients should be monitored carefully after transarterial chemoembolization.     

Computed tomography perfusion in evaluating the therapeutic effect of transarterial chemoembolization for hepatocellular carcinoma

AIM： To prospectively assess the changes in parameters of computed tomography （CT） perfusion pre- and post-transarterial chemoembolization （TACE） of hepatocellular carcinoma （HCC） in different treatment response groups, and to correlate the changes with various responses of HCC to TACE. METHODS： Thirty-nine HCC patients underwent CT perfusion examinations pre-（1 d before TACE） and post-treatment （4 wk after TACE）. The response evaluation criteria for solid tumors （RECIST） were referred to when treatment responses were distributed. Wilcoxon-signed ranks test was used to compare the differences in CT perfusion parameters pre- and post- TACE for different response groups.
RESULTS： Only one case had treatment response to CR and the CT perfusion maps of post-treatment lesion displayed complete absence of signals. In the PR treatment response group, hepatic artery perfusion （HAP）, hepatic arterial fracture （HAF） and hepatic blood volume （HBV） of viable tumors post-TACE were reduced compared with pre-TACE （P = 0.001, 0.030 and 0.001, respectively）. In the SD group, all CT perfusion parameters were not significantly different pre- and post-TACE. In the PD group, HAP, HAl=, portal vein perfusion （PVP） and hepatic blood flow （HBF） of viable tumors post-TACE were significantly increased compared with pre-TACE （P = 0.005, 0.012, 0.035 and 0.005, respectively）.
CONCLUSION： Changes in CT perfusion parameters of viable tumors are correlated with different responses of HCC to TACE. Therefore, CT perfusion imaging is a feasible technique for monitoring response of HCC to TACE.     

Early prediction of survival in hepatocellular carcinoma patients treated with transarterial chemoembolization plus sorafenib

AIM To identify clinical biomarkers that could early predict improved survival in patients with advanced-stage hepatocellular carcinoma(HCC) treated with transarterial chemoembolization combined with sorafenib(TACE-S).METHODS We retrospectively evaluated the medical records of consecutive patients with advanced-stage HCC who underwent TACE-S from January 2012 to December 2015. At the first follow-up 4-6 wk after TACE-S(median, 38 d; range, 33-45 d), patients exhibiting the modified Response Evaluation Criteria in Solid Tumors(m RECIST)-evaluated complete response, partial response, and stable disease were categorized as early disease control. At this time point, multiple variables were analyzed to identify the related factors affecting survival.RESULTS Ninety-five patients were included in this study, and 60 of these patients achieved early disease control, with an overall disease control rate(DCR) of 63.2%. Patients who got sorafenib at the first TACE(no previous TACE) and patients without portal vein tumor thrombus(PVTT) had a higher DCR than those who underwent previous TACE before TACE-S(72.4% vs 48.6%, P = 0.019) and those with PVTT(75.5% vs 50.0%, P = 0.010). Early disease control after TACE-S, no previous TACE, and no PVTT were the independent prognostic factors for survival in the uni-and multivariate analyses.CONCLUSION The first follow-up 4-6 wk after TACE-S can be used as the earliest time point to assess the response to TACE-S, and patients with m RECIST-evaluated early disease control, no previous TACE, and no PVTT had better survival.     

Review of preoperative transarterial chemoembolization for resectable hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the few cancers whose incidence has been continually increasing over recent years.Resection of HCC offers the only hope for cure.However,recurrences are common in patients who have undergone resection.In our opinion,the effectiveness with which transarterial chemoembolization(TACE) as a neoadjuvant therapy for resectable HCC prevents recurrence and prolongs survival has not been conclusively demonstrated.All published meta-analyses have consistently failed to demonstrate that preoperative TACE improves the prognosis of resectable HCC.We believe that these published articles have several limitations and have our own views about the results of meta-analyses.It is very important that the scientific community shed more light on the pathogenesis of HCC and relate this to choice of therapy.This review mainly concerns our understanding of preoperative TACE for resectable HCC and briefly addresses desirable directions for future studies.     

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.     

Chemotherapy for transarterial chemoembolization in patients with unresectable hepatocellular carcinoma

AIM: To compare the efficacy of different chemotherapeutic agents during conventional transarterial chemoembolization (cTACE) in the treatment of unresectable hepatocellular carcinoma (HCC).METHODS: A retrospective review was undertaken of patients with unresectable HCC undergoing cTACE from May 2003 to November 2011. A total of 107 patients were treated with at least one cTACE session. Irinotecan (CPT-11) was used as a chemotherapeutic agent in 24 patients, gemcitabine (GEM) in 24 and doxorubicin in 59.RESULTS: The time to progression and overall survival rates were significantly superior in patients treated with CPT-11 compared with the GEM or doxorubicin treated groups (11.4, 8.2, 9.5 mo, P = 0.02 and 21.7, 12.7, 14.5 mo, P = 0.004, respectively). Subgroup analysis showed that for intermediate-stage HCC, CPT-11 resulted in a significantly longer time to progression and overall survival compared with the GEM or doxorubicin treated groups (P = 0.022; P = 0.003, respectively). There were no significant differences in adverse events among the three groups (P > 0.05).CONCLUSION: For patients treated with cTACE, the chemotherapeutic agent CPT-11 was significantly associated with improved overall survival and delayed tumor progression compared with GEM or doxorubicin. There were no significant differences in clinical adverse events between the three agents. CPT-11 thus appears to be a promising agent when combined with cTACE for the treatment of HCC.     

Sequential use of transarterial chemoembolization and percutaneous cryosurgery for hepatocellular carcinoma

AIM： To evaluate the efficacy of sequential use of transarterial chemoembolization （TACE） and percutaneous cryosurgery for unresectable hepatocellular carcinoma （HCC）. METHODS： Four hundred and twenty patients were enrolled in this study. The patients, who were considered to have unresectable tumors due to their location or size or comorbidity, were divided into sequential TACE-cryosurgery （sequential） group （n = 290） and cryosurgery alone （cryoalone） group （n = 130）. Patients in the sequential group tended to have larger tumors and a greater number of tumors than those in the cryo-alone group. Tumors larger than 10 cm in diameter were only seen in the sequential group. TACE was performed with the routine technique and percutaneous cryosurgery was conducted under the guidance of ultrasound 2-4 wk after TACE. RESULTS： During a mean follow-up period of 42 ± 17 mo （range, 24-70 mo）, the local recurrence rate at the ablated area was 17% for all patients, 11% and 23% for patients in sequential group and cryoalone groups, respectively （P = 0.001）. The overall 1-, 2-, 3-, 4- and 5-year survival rate was 72%, 57%, 47%, 39% and 31%, respectively. The 1- and 2-year survival rates （71% and 61%） in sequential group were similar to those （73% and 54%） in cryo-alone group （P = 0.69 and 0.147）, while the 4- and 5-year survival rates were 49% and 39% in sequential group, higher than those （29% and 23%） in cryo-alone group （P = 0.001）. Eighteen patients with large HCC （〉 5 cm in diameter） survived for more than 5 years after sequential TACE while no patient with large HCC （〉 5 cm in diameter） survived more than 5 years after cryosurgery. The overall complication rate was 24%, and the complication rates were 21% and 26% for the sequential and cryo-alone groups, respectively （P = 0.06）. The incidence of hepatic bleeding was higher in cryo-alone group than in sequential group （P = 0.02）. Liver crack only occurred in two patients of the cryoalone group. CONCLUSION： Pre-cryosurgical TACE can increase the cryoablation efficacy and decrease its adverse effects, especially bleeding. Sequential TACE and cryosurgery may be the better procedure for unresectable HCC, especially for large HCC.     

Outcome of transarterial chemoembolization in patients with inoperable hepatocellular carcinoma eligible for radiofrequency ablation

AIM: To evaluate the outcome of transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC)<5 cm in diameter eligible for radiofrequency ablation (RFA). METHODS: The treatment-related mortality, morbidity, long-term survival, and prognostic factors of HCC patients who had TACE and fulfilled the present inclusion criteria for RFA were evaluated. RESULTS: Of the 748 patients treated with TACE between January 1990 and December 2002,114 patients were also eligible for RFA. The treatment-related mortality and morbidity were 1% and 19%, respectively. Survival at 1, 3, and 5 years was 80%, 43%, and 23%, respectively. Older age and a high albumin level were associated with a better survival, whereas a high a-fetoprotein level (AFP) and the size of the largest tumor >3 cm in diameter were adverse prognostic factors in multivariate analysis. CONCLUSION: The morbidity, mortality, and survival data after TACE for small HCCs eligible for RFA are comparable to those reported after RFA in the literature. Our data suggest the need for a randomized comparison of the two treatment modalities for small HCCs.     

Idarubicin vs doxorubicin in transarterial chemoembolization of intermediate stage hepatocellular carcinoma

BACKGROUND Liver cancer is the fifth most common cancer and the second cause of cancerrelated deaths worldwide.Transarterial chemoembolization(TACE)is the best treatment of intermediate hepatocellular carcinoma(HCC).Doxorubicin is the most commonly used drug despite a low level of evidence.AIM To compare the objective response rate of idarubicin-based TACE(Ida-TACE)against doxorubicin-based TACE(Dox-TACE)in intermediate stage HCC.METHODS Between January 2012 and December 2014,all patients treated with TACE at our academic hospital were screened.Inclusion criteria were patients with Child-Pugh score A or B,a performance status below or equal to 1,and no prior TACE.Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin.Each patient treated with idarubicin was matched with two doxorubicin-treated patients.The TACE response was assessed by independent radiologists according to the mRECIST criteria.RESULTS Sixty patients were treated with doxorubicin and thirty with idarubicin.There were 93%and 87%of cirrhotic patients and 87%and 70%of Child-Pugh A in the doxorubicin and idarubicin groups,respectively.The median number of HCC per patient was two in both groups with 31%and 26%of single nodules in doxorubicin and idarubicin groups,respectively.Objective response rate after first TACE was 76.7%and 73.3%(P=0.797)with 41.7%and 40.0%complete response in doxorubicin and idarubicin groups,respectively.Progression-free survival was 7.7 mo in both groups,and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups,respectively.Safety profiles were similar in both groups,with grade 3-4 adverse events in 35%of Dox-TACE and 43%of Ida-TACEs.CONCLUSION Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety.Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.     

经肝动脉化疗栓塞后联合索拉非尼治疗肝癌患者临床观察

目的探讨索拉非尼联合经肝动脉化疗栓塞术（TACE）治疗肝癌患者的效果。方法选取142例肝癌患者,其中57例接受TACE治疗,47例接受索拉非尼治疗,38例接受索拉非尼联合TACE治疗。在治疗后12 w,评估治疗效果、总生存期（OS）和疾病进展时间（TTP）。结果联合治疗组有效率为26.32%,显著高于TACE组的17.54%或索拉非尼组的19.15%（P<0.05）;联合治疗组疾病控制率为71.05%,显著高于TACE组的57.89%或索拉非尼组的53.19%（P<0.01）;联合治疗组患者OS为8.6 m,显著高于索拉非尼组的6.2 m或TACE组的7.3 m（P<0.05）;联合治疗组TTP为6.7 m,显著高于索拉非尼组的5.1m或TACE组的 5.6 m（P<0.01）。结论索拉非尼联合TACE治疗肝癌患者具有较好的临床效果。     

Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization

AIM To investigate novel predictors of survival in hepatocellular carcinoma(HCC) patients following transarterial chemoembolization(TACE).METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results(total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index(AgI). We used The Wilcoxon ranksum(Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival. RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI or 4 was 42.4% vs 61.8%; P 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56(95%CI: 1.120-5.863 P 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase(GGTP) had ORs of 1.01(95%CI: 1.003-1.026, P 0.017) and 0.99(95%CI: 0.99-1.00, P 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI 4 had HR for mortality of 2.18(95%CI: 1.108-4.310, P 0.024). GGTP's single unit change had a HR for mortality of 1.003(95%CI: 1.001-1.006, P 0.016). These were considered in the final multivariate model with the total cohort. An AgI 4 had a HR for mortality of 2.26(95%CI: 1.184-4.327, P 0.016). GGTP had a HR of 1.003(95%CI: 1.001-1.004, P 0.001).CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.     

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.     

Adjuvant transarterial chemoembolization after curative resection of hepatocellular carcinoma: Propensity score analysis

AIM: To compare survival and recurrence in hepatocellular carcinoma (HCC) patients who did or did not receive adjuvant transarterial chemoembolization (TACE).METHODS: A consecutive sample of 229 patients who underwent curative resection between March 2007 and March 2010 in our hospital was included. Of these 229 patients, 91 (39.7%) underwent curative resection followed by adjuvant TACE and 138 (60.3%) underwent curative resection alone. In order to minimize confounds due to baseline differences between the two patient groups, comparisons were conducted between propensity score-matched patients. Survival data and recurrence rates were compared using the Kaplan-Meier method. Independent predictors of overall survival and recurrence were identified using Cox proportional hazard regression.RESULTS: Among 61 pairs of propensity score-matched patients, the 1-, 2-, and 3-year overall survival rates were 95.1%, 86.7%, and 76.4% in the TACE group and 86.9%, 78.5%, and 73.2% in the control group, respectively. At the same time, the TACE and control groups also showed similar recurrence rates at 1 year (13.4% vs 24.8%), 2 years (30.6% vs 32.1%), and 3 years (40.1% vs 34.0%). Multivariate Cox regression identified serum alpha-fetoprotein level ≥ 400 ng/mL and tumor size > 5 cm as independent risk factors of mortality (P < 0.05).CONCLUSION: As postoperative adjuvant TACE does not improve overall survival or reduce recurrence in HCC patients, further study is needed to clarify its clinical benefit.     

Milan criteria are useful predictors for favorable outcomes in hepatocellular carcinoma patients undergoing liver transplantation after transarterial chemoembolization

INTRODUCTION Hepatocellular carcinoma (HCC) is a major global health problem involving more than 500 000 new cases a year. Several treatment modalities, such as liver transplantation (LT), surgical resection, radiofrequency ablation (RFA), and percutaneou…     

Poor prognosis for hepatocellular carcinoma with transarterial chemoembolization pre-transplantation:Retrospective analysis

AIM: To investigate whether transarterial chemoembolization(TACE) before liver transplantation(LT) improves long-term survival in hepatocellular carcinoma(HCC) patients.METHODS: A retrospective study was conducted among 204 patients with HCC who received LT from January 2002 to December 2010 in PLA General Hospital. Among them, 88 patients received TACE before LT. Prognostic factors of serum α-fetoprotein(AFP), intraoperative blood loss, intraoperative blood transfusion, disease-free survival time, survival time with tumor, number of tumor nodules, tumor size, tumor number, presence of blood vessels and bile duct invasion, lymph node metastasis, degree of tumor differentiation, and preoperative liver function were determined in accordance with the Child-TurcottePugh(Child) classification and model for end-stage liver disease. We also determined time of TACE before transplant surgery and tumor recurrence and metastasis according to different organs. Cumulative survival rate and disease-free survival rate curves were prepared using the Kaplan-Meier method, and the logrank and χ2 tests were used for comparisons.RESULTS: In patients with and without TACE before LT, the 1, 3 and 5-year cumulative survival rate was 70.5% ± 4.9% vs 91.4% ± 2.6%, 53.3% ± 6.0% vs 83.1% ± 3.9%, and 46.2% ± 7.0% vs 80.8% ± 4.5%, respectively. The median survival time of patients with and without TACE was 51.857 ± 5.042 mo vs 80.930 ± 3.308 mo(χ2 = 22.547, P < 0.001, P < 0.05). The 1, 3 and 5-year disease-free survival rates for patients with and without TACE before LT were 62.3% ± 5.2% vs98.9% ± 3.0%, 48.7% ± 6.7% vs 82.1% ± 4.1%, and 48.7% ± 6.7% vs 82.1% ± 4.1%, respectively. The median survival time of patients with and without TACE before LT was 50.386 ± 4.901 mo vs 80.281 ± 3.216 mo(χ2 = 22.063, P < 0.001, P < 0.05). TACE before LT can easily lead to pulmonary or distant metastasis of the primary tumor. Although there was no significant difference between the two groups, the chance of metastasis of the primary tumor in the group with TACE was significantly higher than that of the group without TACE.CONCLUSION: TACE pre-LT for HCC patients increased the chances of pulmonary or distant metastasis of the primary tumor, thus reducing the long-term survival rate.