Postoperative Transarterial Chemoembolization Research Articles

Down-regulation of ALDOB during metabolic reprogramming mediates malignant behavior in hepatocellular carcinoma and insensitivity to postoperative adjuvant transarterial chemoembolization.

Postoperative transarterial chemoembolization (PA-TACE) is an effective adjuvant therapy for preventing early postoperative recurrence of hepatocellular carcinoma (HCC); however, many patients are insensitive to it. Therefore, the present study aimed to explore the in-depth reasons for PA-TACE resistance and provide a reliable basis for selecting patients who will benefit the most from PA-TACE. The unique gene expression profiles of primary tumors from PA-TACE-sensitive or -insensitive patients were analyzed using microarray data. Combined differential expression analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were used to screen for potential drivers of PA-TACE insensitivity. The expression of ALDOB was silenced or overexpressed in hepatoma cell lines, and changes in glycolytic activity, cycle, apoptosis, and malignant biological phenotypes were observed under normoxia and hypoxia. Finally, an animal model was constructed to verify the effects of ALDOB dysregulation on the tumorigenic ability of HCC cells in vivo. The inhibition of ALDOB promoted the up-regulation of Ki67 expression, and glycolytic activity was significantly enhanced. Moreover, the proliferation, invasion, and migration capabilities were increased in HCC cells and even worse in hypoxia. This advantage of malignant behavior was also validated using in vivo models. Down-regulation of ALDOB may underlie the metabolic reprogramming observed in HCC by promoting the malignant behavior of HCC cells. Hypoxia and ALDOB down-regulation acted additively, which was closely related to PA-TACE insensitivity. The use of ALDOB and Ki67 as a combined marker has the potential to identify the 'PA-TACE beneficiary population'.

Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Simple SummaryThe role of postoperative transarterial chemoembolization (TACE) after liver resection for hepatocellular carcinoma (HCC) remains unclear. We performed a systematic review of the literature and compared the survival outcomes of TACE vs. no TACE after liver resection for HCC. While the existing evidence suggests a benefit of adjuvant TACE, published trials to date are at significant risk of bias and limited to Eastern Asian patients. High-quality randomized clinical trials are needed to confirm the oncologic benefits of adjuvant TACE.The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.

Influence of postoperative adjuvant transarterial chemoembolization on the prognosis of early-stage intrahepatic cholangiocarcinoma: a single center study.

The effectiveness of postoperative adjuvant transarterial chemoembolization (TACE) on survival and recurrence in tumor-node-metastasis (TNM) stage I intrahepatic cholangiocarcinoma (ICC) after radical resection remains unclear. This study aimed to compare overall survival (OS) and recurrence-free survival (RFS) in TNM stage I ICC patients with and without postoperative TACE. A retrospective cohort study was conducted on TNM stage I ICC patients who had undergone R0 resections with curative intent in Shanghai Eastern Hepatobiliary Surgery Hospital from January 2012 to December 2016. A total of 269 patients were divided into two groups: (I) 35 patients who received postoperative TACE and (II) 234 patients no TACE. Staging was performed according to the 8th edition of American Joint Committee on Cancer (AJCC) TNM staging system. The tumor-related RFS and OS were estimated by the Kaplan-Meier method. Cox proportional regression model was employed to evaluate the prognosis between the two groups. In all patients, the median OS was 66.8 months. After R0 resection, adjuvant TACE could not improve the survival of TNM stage I patients, and the OS of the TACE group was not better than that of the non-TACE group (P=0.7070). In addition, in the TACE group, the recurrence rate of TNM stage I ICC patients was statistically significantly higher than that of the non-TACE group (P=0.0328). Multivariable analysis revealed that adjuvant TACE was an independent predictor of worse RFS (HR: 1.88, 95% CI: 1.21-2.93). Adjuvant TACE after radical surgery failed to prolong the OS and potentially delay recurrence for patients with TNM Stage I ICC. Adjuvant TACE might not be suitable for patients with TNM Stage I ICC.

Preoperative Versus Postoperative Transarterial Chemoembolization on Prognosis of Large Hepatocellular Carcinoma.

Background: Transarterial chemoembolization (TACE) has proven to be an effective adjuvant therapy with liver resection (LR) to treat patients with hepatocellular carcinoma (HCC). The aim of this study was to evaluate outcomes in patients with HCC larger than 5 cm, comparing those who had TACE before LR to those who had TACE after LR.Materials and methods: A total of 320 consecutive patients who underwent LR in combination with TACE for HCC larger than 5 cm from January 2009 to December 2014 were enrolled in study. Patients were divided into two groups: preoperative TACE group (n=199) and postoperative TACE group (n=121). Overall survival (OS) and recurrence-free survival (RFS) of patients were compared between preoperative TACE and postoperative TACE groups by propensity score-matching (PSM). We determined prognostic factors for recurrence and death using multivariate cox regression analysis.Results: Among the 320 patients, the median age was 48 (range, 18 to 75) years, and 285 (89.1%) patients were male. During the follow- up period, 88 (44.2%) patients in the preoperative TACE group and 69 (57.0%) patients in the postoperative TACE group died. Before PSM, both OS and RFS were significantly longer in the preoperative TACE group than those in the postoperative TACE group (P=0.001 and P<0.001, respectively). After PSM, compared to those received postoperative TACE, patients with preoperative TACE had significantly better OS (Hazard ratio [HR]=1.92; 95% confidence interval [CI], 1.22-3.02; P=0.005) and RFS (HR=1.64; 95% CI, 1.16-2.32; P=0.005).Conclusions: Patients with large HCC undergoing LR appear to derive greater disease control and survival benefit from a single preoperative TACE treatment than from postoperative TACE.

The clinical characteristics and prognostic factors of combined Hepatocellular Carcinoma and Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma after Surgical Resection: A propensity score matching analysis.

Background: Clinical characteristics and prognosis among combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CC) with HCC and intrahepatic cholangiocarcinoma (ICC) were inconsistent in previous studies. The aim of this study was to compare postoperative prognosis among cHCC-CC, HCC and ICC, and investigated the prognostic risk factor of cHCC-CC after surgical resection.Methods: A total of 1041 eligible patients with pathological diagnosis of cHCC-CC (n=135), HCC (n=698) and ICC (n=208) were enrolled in this study. Univariate and multivariate Cox analysis were applied for assessing important risk factors. cHCC-CC were further 1:1 matched with HCC and ICC on important clinical risk factors. Survival curves of matched and unmatched cohorts were depicted by Kaplan-Meier method with log-rank test.Results: Patients with cHCC-CC had similar rate of sex, age and cirrhosis with HCC (p<0.05) and comparable incidence of hepatitis B or C with ICC (p=0.197). Patients of cHCC-CC had intermediate prognosis between HCC and ICC, with median overall survival (OS) time of cHCC-CC, HCC and ICC of 20.5 months, 35.7 months and 11.6 months (p<0.001). In matched cohorts, the OS of cHCC-CC were worse than HCC (p<0.001) but comparable with ICC (p=0.06), while the disease-free survival (DFS) of cHCC-CC was worse than HCC but better than ICC (p<0.05). And lymph node infiltration and postoperative transarterial chemoembolization (TACE) were independent risk factors of cHCC-CC associated with prognosis.Conclusion: The long term survival of cHCC-CC was worse than HCC but comparable with ICC when matched on albumin level, tumor size, lymph node infiltration, tumor stage and margin. Presence of lymph node infiltration and no postoperative TACE were associated with poor prognosis of cHCC-CC.

The Clinical Value of Postoperative Transarterial Chemoembolization for Resectable Patients with Intermediate Hepatocellular Carcinoma After Radical Hepatectomy: a Propensity Score-Matching Study

Background and AimsSurgical resection for patients with intermediate hepatocellular carcinoma (HCC) is preferred in China, but the prognosis remains far from satisfactory. Postoperative transarterial chemoembolization (p-TACE) has been conducted prevalently to prevent recurrence, but its efficacy remains controversial. Hence, we collected the data from primary liver cancer big data (PLCBD) to investigate the clinical value of p-TACE for patients with intermediate HCC and identify the potential beneficiaries. MethodsPatients who were diagnosed with intermediate HCC between December 2012 and December 2015 were identified through the PLCBD. Disease-free survival (DFS) of patients who received p-TACE or not following radical resection was evaluated using Kaplan-Meier survival curves before and after 1:1 propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors associated with recurrence. ResultsA total of 325 intermediate HCC patients receiving radical resection were eligible in this study, including 123 patients in the p-TACE group and 202 in the non-TACE group. Median DFS in the p-TACE group was significantly longer than in the non-TACE group (23.3 months vs. 18.0 months, P = 0.016) in the whole cohort with no severe complicates, which was confirmed in a well-matched cohort (17.4 months vs. 23.3 months, P = 0.012). In addition, p-TACE was identified as an independent risk factors of DFS by multivariate Cox regression analysis before and after PSM (both P < 0.05). After adjusting for other prognostic variables, patients were found to significantly benefit from p-TACE in DFS if they were male, or had hepatitis, diabetes, cirrhosis, AFP ≤ 400 ng/ml, anatomic hepatectomy, no severe surgical complication, no intraoperative transfusion, tumor number = 2, differentiation grading III, capsule, or had no transfusion (all P < 0.05). ConclusionWith the current data, we concluded that p-TACE was safe and efficient for the patients with intermediate HCC following radical resection, and male patients with hepatitis, diabetes, cirrhosis, AFP ≤ 400 ng/ml, anatomic hepatectomy, no severe surgical complication, no intraoperative transfusion, tumor number = 2, differentiation grading III, and capsule would benefit more from p-TACE.

Postoperative adjuvant therapy following radical resection for intrahepatic cholangiocarcinoma: A multicenter retrospective study.

Background and AimsThe prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory; however, the clinical value of adjuvant therapy (AT) remains controversial. This multicenter study aimed to evaluate the clinical value of AT and identify potential patients who would be benefited from AT.MethodsData from ICC patients who underwent radical resection were retrospectively collected from 12 hepatobiliary centers in China between December 2012 and December 2015. Patients were divided into AT and non‐AT groups based on whether AT was administered or not. Overall survival (OS) and disease‐free survival (DFS) were analyzed using the Kaplan‐Meier method before and after 1:2 propensity score matching (PSM). Subgroup analyses were conducted based on the established staging systems.ResultsA total of 412 patients were enrolled in this study, and 77 patients (18.9%) received AT, including 32 (7.8%) patients who received transarterial chemoembolization (TACE), 21 (5.1%) patients who received chemotherapy, 10 (2.4%) patients who received radiotherapy, and 14 (3.4%) patients who received adjuvant chemoradiotherapy. The median OS and DFS were both longer in the AT group than in the non‐AT group (43.0 months vs 21.0 months, P = .015; 16.0 months vs 11.0 months, P = .045, respectively), and the advantage of AT was confirmed for both the OS and DFS (P = .023; P = .046, respectively) after 1:2 PSM. Furthermore, based on the established nomogram, only “middle‐risk” patients receiving AT cherished a longer median OS (43.0 months vs 20.0 months, P = .033). In subgroup analyses that were stratified by different AT strategies, patients receiving postoperative chemotherapy had a longer median OS (37.0 months vs 21.0 months, P = .039), while patients receiving postoperative TACE had a longer median DFS (50.0 months vs 11.0 months, P = .007).ConclusionWith the current data, we conclude that AT benefits ICC patients following radical resection, especially those “middle‐risk” patients, as evaluated by the established nomogram. However, exactly which patients are the most suitable for AT requires further study and validation.

Adjuvant transarterial chemoembolization following radical resection for intrahepatic cholangiocarcinoma: A multi-center retrospective study.

Background and Aims: The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory, but the effect of postoperative transarterial chemoembolization (p-TACE) remains controversial. This multi-center retrospective study was to evaluate the clinical value of p-TACE and identify the selected patients who would benefit from p-TACE.Methods: Data of ICC patients who underwent radical resection with/without p-TACE therapy was obtained from 12 hepatobiliary centers in China between Jan 2014 and Jan 2017. Overall survival (OS) was set as the primary endpoint, which was analyzed by the Kaplan-Meier method before and after propensity score matching (PSM). Subgroup analysis was conducted based on the established staging system and survival risk stratification.Results: A total of 335 patients were enrolled in this study, including 39 patients in the p-TACE group and 296 patients in the non-TACE group. Median OS in the p-TACE group was longer than that in the non-TACE group (63.0 months vs. 18.0 months, P=0.041), which was confirmed after 1:1 PSM (P=0.009). According to the 8th TNM staging system, patients with stage II and stage III stage would be benefited from p-TACE (P=0.021). Subgroup analysis stratified by risk factors showed that p-TACE could only benefit patients with risk factors <2 (P=0.027).Conclusion: Patients with ICC should be recommended to receive p-TACE following radical resection, especially for those with stage II, stage III or risk factors <2. However, the conclusion deserved further validation.

Prognostic Nomogram for Hepatitis B Virus-related Hepatocellular Carcinoma With Adjuvant Transarterial Chemoembolization After Radical Resection.

The objective of this study was to establish a reliable and effective nomogram for predicting prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with postoperative adjuvant transarterial chemoembolization (TACE). A derivation cohort of 370 HCC patients treated with postoperative TACE in the Eastern Hepatobiliary Surgery Hospital from January 2009 to December 2012 were retrospectively analyzed. Univariate and multivariate analysis were performed by Cox regression and independent prognostic factors for overall survival were determined to construct the nomogram. Concordance index (C-index), calibration curve and decision curve analysis were performed to evaluate the capability of the nomogram and the established nomogram was compared with TNM stage and Barcelona Clinic Liver Cancer (BCLC) stage to identify the superior model. The results were validated in a validation cohort of 123 HCC patients in the same center. Multivariate analysis indicated that γ-glutamyl transferase, α-fetoprotein, tumor number, tumor size, satellite lesions, microvascular invasion, and HBV-DNA were independent prognostic factors for overall survival in the derivation cohort, and all these factors were selected into the nomogram. The C-index was 0.755 for survival prediction of the nomogram, which was significantly higher than the TNM stage (0.636, P<0.001) and BCLC stage (0.594, P<0.001). A fair uniformity and a superior net benefit with wide range threshold probabilities were showed in the calibration curves and decision curve analysis. In the validation cohort, the C-index of the nomogram (0.785) also had a higher predictive accuracy than TNM stage (0.744, P=0.019) and BCLC stage (0.616, P<0.001). The nomogram with accurate and reasonable performance was proposed for predicting survival of HBV-related HCC with postoperative adjuvant TACE.

Beneficial effects of Cripto-1 for transarterial chemoembolization in hepatocellular carcinoma.

Cripto-1 may act as an independent predictor for prognosis in hepatocellular carcinoma (HCC). However, the function of Cripto-1 in HCC cells and its response to postoperative transarterial chemoembolization (TACE) in HCC patients remains unclearly. Up-regulated Cripto-1 expression boosted the ability of cell proliferation, migration and invasion in HCC cells in vitro. While opposite results were observed in HCC cells with down-regulated Cripto-1 expression. Cripto-1 expression was correlated with epithelial-mesenchymal transition (EMT) relevant biomarkers. Furthermore, in high Cripto-1 expression patients, those with adjuvant TACE had favorable TTR and OS times. On contrary, adjuvant TACE may promote tumor recurrence but had no influence on OS time in patients with low Cripto-1 expression. In different subgroups of vascular invasion, larger tumor size or liver cirrhosis, patients with adjuvant TACE had longer TTR and OS times than those without TACE in patients with high Cripto-1 expression, while they could not obtain benefits from adjuvant TACE in patients with low-expressed Cripto-1 expression. In conclusion, Cripto-1 may be a potential prognostic factor in predicting outcome of HCC patients with TACE therapy, and combined with Cripto-1 and tumor features may be helpful to stratify patients with respect to prognosis and response to adjuvant TACE.

ID3 Promotes Stem Cell Features and Predicts Chemotherapeutic Response of Intrahepatic Cholangiocarcinoma.

Cancer stem cells contribute to a high rate of recurrence and chemotherapeutic resistance in many types of cancer, including intrahepatic cholangiocarcinoma (ICC). Inhibitor of differentiation 3 (ID3) has been reported to promote cancer stem cells, but its role in ICC is obscure. In this study, we identified that ID3 is highly expressed in human ICC tissues compared with matched normal tissues and correlates with poor prognosis. Functional studies demonstrate that ID3 is required for stemness maintenance in cholangiocarcinoma both in vitro and in vivo. Consistent with the regulation of cancer stem cell features by ID3, transgenic expression of ID3 enhances chemoresistance of cholangiocarcinoma cells. Moreover, we found that ICC patients with low ID3 levels benefited from postoperative transarterial chemoembolization, whereas patients with high ID3 levels did not, indicating the significance of ID3 in individualized ICC therapy. Mechanistically, ID3 could interact with E47 and block E47 recruitment to the promoter of β-catenin, which leads to activation of Wnt/β-catenin signaling. Conclusion: Our results show that ID3 could promote the stemness of ICC by increasing the transcriptional activity of β-catenin and could serve as a biomarker in predicting ICC patients' response to adjuvant chemotherapeutics.

Adjuvant transarterial chemoembolization to improve the prognosis of hepatocellular carcinoma following curative resection.

The present study aimed to investigate the prognostic factors for recurrence of hepatocellular carcinoma (HCC) following curative resection, and evaluate the efficacy of postoperative adjuvant transarterial chemoembolization (TACE) in improving prognosis. A total of 166 patients who underwent curative resection followed by adjuvant TACE, and 190 patients who underwent curative resection alone were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors of recurrence. Separated based on risk factors, subgroup studies were conducted and the association between TACE and recurrence rates was examined. Postoperative overall survival rates were determined using the Kaplan-Meier method and differences between the two therapeutic strategies were identified through log-rank analysis. Computerized tomography (CT)/magnetic resonance imaging (MRI) images were used to evaluate the function of postoperative adjuvant TACE for enhancing the efficacy of CT/MRI in detecting recurrence. The results of the univariate and multivariate analyses revealed that tumor capsule invasion, vascular invasion, and multiple nodules were risk factors of early recurrence. For patients with these risk factors, recurrence rates were markedly decreased at 6 and 12 months, but not at 18 and 24 months, if TACE was added to curative resection. The hepatitis B virus (HBV) was a risk factor for late recurrence. Postoperative TACE was not effective in reducing the recurrence rate in patients with HBV. Survival increased following curative resection with TACE compared with curative resection alone. Furthermore, adjuvant TACE enhanced the efficacy of CT/MRI in detecting recurrence. Postoperative adjuvant TACE may improve the prognosis of HCC following curative resection.

Postoperativer TACE in hepatocellular carcinoma: a Meta-analysis

Objective To evaluate the therapeutic effects of postoperative TACE (transarterial chemoembolization) in patients with hepatocellular carcinoma after liver resection. Methods The search was conducted on China biomedical literature database, Chinese CNKI, VIP, Wanfang and PubMed, OVID, Embase and Cochrane library. All the literatures were searched till the end of January 2016. The quality of the included studies were evaluated using the modified Jadad score for randomized controlled trials and the Newcastle-Ottawa Scale for case controlled studies. The trials were analyzed by Stata12.0. Results A total of 2184 patients from 1 randomized controlled trial (RCT) and 14 case-control studies were included. These patients were divided into two groups based on the treatment method. 469 patients were included into the hepatic resection only group and 1087 patients were into the postoperative TACE group. The results showed that postoperative TACE improved the 1-year survival for hepatocellular carcinoma. Subgroup analyses were conducted on the risk factor group (tumor diameter greater than 5cm; multiple nodules and blood vessel invasion) and the no risk factor group. Postoperative TACE played an important role in the risk factor group (subgroup analysis for the no risk factor group: RR=1.10, 95%CI: 0.97, 1.25, P>0.05; subgroup analysis for the risk factor group: RR=1.16, 95%CI: 1.02, 1.32, P 0.05). Conclusions Postoperative TACE prolonged the survival rate of patients with hepatocellular carcinoma, especially those who had the following risk factors: tumor diameter greater than 5 cm; multiple nodules; blood vessel invasion. Postoperative TACE can be recommended as a routine treatment. Key words: Primary hepatocellular carcinoma; Liver resection; Transarterial chemoembolization (TACE); Meta-analysis; Curative effect

Hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus.

Despite surgical removal of tumors with portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients, early recurrence tends to occur, and overall survival (OS) periods remain extremely short. The role that hepatectomy may play in long-term survival for HCC with PVTT has not been established. The operative mortality of hepatectomy for HCC with PVTT has also not been reviewed. Hence, we reviewed recent literature to assess these parameters. The OS of patients who received hepatectomy in conjunction with multidisciplinary treatment tended to be superior to that of patients who did not. Multidisciplinary treatments included the following: preoperative radiotherapy on PVTT; preoperative transarterial chemoembolization (TACE); subcutaneous administration of interferon-alpha (IFN-α) and intra-arterial infusion of 5-fluorouracil (5-FU) with infusion chemotherapy in the affected hepatic artery; cisplatin, doxorubicin and 5-FU locally administered in the portal vein; and subcutaneous injection of IFN-α, adjuvant chemotherapy (5-FU + Adriamycin) administration via the portal vein with postoperative TACE, percutaneous isolated hepatic perfusion and hepatic artery infusion and/or portal vein chemotherapy. The highest reported rate of operative mortality was 9.3%. In conclusion, hepatectomy for patients affected by HCC with PVTT is safe, has low mortality and might prolong survival in conjunction with multidisciplinary treatment.

Transarterial Chemoembolization: A Favorable Postoperative Management to Improve Prognosis of Hepatitis B Virus-associated Intrahepatic Cholangiocarcinoma after Surgical Resection.

Background: There is no information regarding transarterial chemoembolization (TACE) as a postoperative management after hepatic resection for patients with hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC).Methods: Forty-two patients with pathological confirmation of HBV-associated ICC were enrolled. Prognostic impact of the clinicopathological factors as well as postoperative TACE were evaluated. Computed tomography findings of HBV-associated ICC were assessed.Results: Tumor size of larger than 5 cm (hazard ratio [HR], 5.654; 95% confidence interval [CI], 1.175 to 27.204; P = 0.031), postoperative TACE (HR, 0.123; 95% CI, 0.023 to 0.643; P = 0.013), and lymph node metastasis (HR, 3.284; 95% CI, 1.236 to 8.724; P = 0.017) revealed to be independently associated with survival outcomes of patients with HBV-associated ICC. Application of TACE, as a postoperative management to control early local recurrence on the basis of hepatic arterial phase enhancement, significantly prolonged survival outcomes (1-yr, 88.9%; 3-yr, 77.8%; 5-yr, 66.7%), compared to the patients who did not receive TACE (1-yr, 63.6%; 3-yr, 30.8%; 5-yr, 13.0%). When analyzed according to the status of hepatic arterial phase, arterial phase enhancement demonstrated a favorable trend on prognosis of patients with HBV-associated ICC without statistical significance (HR, 0.435; 95% CI, 0.140 to 1.359; P = 0.141), and TACE independently improved overall survival of patients with arterial phase enhancement (HR, 0.105; 95% CI, 0.014 to 0.774; P = 0.027).Conclusions: Put together, our results indicate that postoperative TACE effectively improves prognosis of HBV-associated ICC with arterial phase enhancement in CT scans. Large-sized trials are required for our results to be applied in clinical medicine.

Hepatic resection alone versus in combination with pre- and post-operative transarterial chemoembolization for the treatment of hepatocellular carcinoma: A systematic review and meta-analysis

The prognosis of hepatocellular carcinoma (HCC) treated with hepatic resection may be improved by the adjunctive use of transarterial chemoembolization (TACE). This study aimed to systematically compare the outcomes between hepatic resection with and without TACE groups. All relevant randomized controlled trials (RCTs) and non-RCTs were searched by the PubMed, EMBASE, and Cochrane Library databases. Overall survival (OS) and disease-free survival (DFS) were two major outcomes. Meta-analyses were performed according to the timing of TACE (pre- or post-operative TACE). Subgroup analyses were also performed. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated. Overall, 55 papers were included (14 RCTs and 41 non-RCTs). Overall meta-analyses demonstrated that OS and DFS were statistically similar between hepatic resection with and without pre-operative TACE groups (HR = 1.01, 95%CI = 0.87-1.19, P = 0.87; HR = 0.91, 95%CI = 0.82-1.01, P = 0.07). Subgroup analyses of RCTs or non-RCTs showed that OS and DFS remained statistically similar between hepatic resection with and without pre-operative TACE groups. Subgroup analysis of incomplete or no tumor necrosis showed that OS was worse in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group. By contrast, subgroup analysis of complete tumor necrosis showed that DFS was better in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group.Overall meta-analyses demonstrated that OS and DFS were better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group (HR = 0.85, 95%CI = 0.72-1.00, P = 0.06; HR = 0.83, 95%CI = 0.73-0.94, P = 0.004). Subgroup analyses of RCTs, vascular invasion, or large HCC showed that OS and DFS remained better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group. By contrast, subgroup analyses of non-RCTs, no vascular invasion, or small HCC showed that OS and DFS were statistically similar between the two groups. Post-operative TACE, rather than pre-operative TACE, may be considered as an adjunctive treatment option for HCC treated with hepatic resection.

Comparative efficacy of postoperative transarterial chemoembolization with or without antiviral therapy for hepatitis B virus-related hepatocellular carcinoma.

This study aims to investigate the efficacy of adjuvant transarterial chemoembolization (TACE) with or without antiviral therapy for patients with hepatocellular carcinoma (HCC) after radical hepatectomy. This retrospective study examined 176 patients after radical hepatectomy, 118 of whom were treated using TACE alone and 58 using TACE combined with antiviral therapy. To reduce confounding bias due to baseline differences, propensity score matching was used to generate 51 pairs of patients from both treatment groups. Overall survival (OS) and disease-free survival (DFS) were analyzed for both groups before and after propensity score matching. Analysis of all patients showed that OS was better in the combination therapy group than in the TACE-only group (P = 0.048), while DFS was similar between the two groups (P = 0.322). Analysis of only propensity score-matched pairs confirmed the significantly better 5-year OS in the combination therapy group (64.6 vs. 37.5 %, P = 0.033) and also suggested better 5-year DFS (37.9 vs. 14.6 %, P = 0.048). Among patients experiencing HCC recurrence, radical surgery was the treatment choice for a significantly larger proportion of patients from the combination therapy group than from the TACE-only group (P = 0.018). Our results suggest that combining antiviral therapy with TACE significantly improves OS and potentially DFS relative to TACE alone in patients with HCC. Combination therapy also appears to leave patients with greater remnant liver function, increasing the possibility of curative resection in the event of recurrence. Combination therapy may be useful for preventing HCC recurrence after radical hepatectomy.

Prognostic significance of Cbx4 expression and its beneficial effect for transarterial chemoembolization in hepatocellular carcinoma.

Our recent investigations showed that polycomb chromobox 4 (Cbx4) promotes angiogenesis and metastasis of hepatocellular carcinoma (HCC) through its sumoylating action on hypoxia-inducible factor-1α protein. Here, we attempt to identify the prognostic significances of Cbx4 by a retrospective analyses in 727 cases of HCC patients with and without postoperative transarterial chemoembolization (TACE) or transarterial embolization (TAE). Binary logistic regression tests indicated that Cbx4 is correlated with histological grading, tumor-node-metastasis stage, microvessel density, distant metastasis and hematogenous metastasis of HCC. By univariate and multivariate analyses, we show that Cbx4 is an independent prognostic factor of HCC, and both TAE and TACE treatments have no effects on the overall survival in HCC patients with low Cbx4 expression. More intriguingly, TACE prolongs, while TAE shortens, the overall survival of HCC patients with high Cbx4 expression, indicating that Cbx4 is a good biomarker on decision-making to perform postoperative TACE in HCC patients. Moreover, Cbx4 overexpression enhances while Cbx4 silencing antagonizes doxorubicin-induced cell death of HCC cell lines. In conclusion, Cbx4 is an independent prognostic factor for HCC patients, and the patients with high Cbx4 expression should receive postoperative TACE treatment to improve their survival.

Retraction note to: clinical value of circulating tumor cells for the prognosis of postoperative transarterial chemoembolization therapy.

The aim of this study was to clarify circulating tumor cells (CTCs) count could reflect the effect of postoperative transarterial chemoembolization therapy. A single-blind, two-parallel group, randomized trial was conducted in Guangdong General Hospital, Guangzhou, China, with patients: (1) with biopsy-confirmed hepatocellular carcinoma (HCC) and (2) undergoing partial resection. Patients in transarterial chemoembolization (TACE) group received TACE 1 month after resection, while control group received no managements. The time points for blood collection to count CTCs were as follows: (1) 1 month after resection (also 1 day before TACE); (2) 1 month after TACE; (3) 2 months after TACE; (4) 3 months after TACE; (5) 6 months after TACE; and (6) 1 year after TACE. A diagnosis of recurrence was based on computed tomography scans, magnetic resonance imaging, or digital subtraction angiography. We compared recurrence rate (RR) and CTC counts between groups. Between July 2010 and July 2012, 171 patients (TACE group: n = 81; control group: n = 90) were recruited. After TACE, mean CTC count in TACE group was 1.32 (CI 2.59–3.34), compared with 3.65 (CI 3.43–3.88) in control group (F = 200.89, P<0.05). CTCs counts were statistically significantly between groups at post-TACE time points. In addition, RR of TACE group was 25.9 % (21/81), while the number was 56.7 % (51/90) in control group. RR was statistically significantly between groups (P = 0.031). CTCs count was an important prognostic parameter for postoperative TACE on HCC recurrence.

Clinical value of circulating tumor cells for the prognosis of postoperative transarterial chemoembolization therapy.

The aim of this study was to clarify circulating tumor cells (CTCs) count could reflect the effect of postoperative transarterial chemoembolization therapy. A single-blind, two-parallel group, randomized trial was conducted in Guangdong General Hospital, Guangzhou, China, with patients: (1) with biopsy-confirmed hepatocellular carcinoma (HCC) and (2) undergoing partial resection. Patients in transarterial chemoembolization (TACE) group received TACE 1 month after resection, while control group received no managements. The time points for blood collection to count CTCs were as follows: (1) 1 month after resection (also 1 day before TACE); (2) 1 month after TACE; (3) 2 months after TACE; (4) 3 months after TACE; (5) 6 months after TACE; and (6) 1 year after TACE. A diagnosis of recurrence was based on computed tomography scans, magnetic resonance imaging, or digital subtraction angiography. We compared recurrence rate (RR) and CTC counts between groups. Between July 2010 and July 2012, 171 patients (TACE group: n = 81; control group: n = 90) were recruited. After TACE, mean CTC count in TACE group was 1.32 (CI 2.59-3.34), compared with 3.65 (CI 3.43-3.88) in control group (F = 200.89, P<0.05). CTCs counts were statistically significantly between groups at post-TACE time points. In addition, RR of TACE group was 25.9 % (21/81), while the number was 56.7 % (51/90) in control group. RR was statistically significantly between groups (P = 0.031). CTCs count was an important prognostic parameter for postoperative TACE on HCC recurrence.