Sorafenib Combined with Transarterial Chemoembolization versus Transarterial Chemoembolization Alone for Advanced-Stage Hepatocellular Carcinoma: A Propensity Score Matching Study

Aims

The purpose of the present study was to compare the efficacies of transarterial chemoembolization (TACE) combined with sorafenib versus TACE monotherapy for treating patients with advanced hepatocellular carcinoma (HCC).

Methods

We enrolled 321 patients and selected 280 with advanced HCC (Barcelona Clinic Liver Cancer stage C) who underwent TACE therapy between February 2009 and February 2013. TACE alone (monotherapy group) was administered to 198 patients (70.7%), and the remaining 82 (29.3%) underwent repeat combined TACE and sorafenib therapy (combined group). To minimize selection bias, these latter 82 patients were matched using propensity-score matching at a 1∶2 ratio with 164 patients who received TACE monotherapy. The primary endpoints were overall survival (OS) and related subgroup analysis. The secondary endpoints were time to progression (TTP) and treatment-related adverse events.

Results

Of the respective patients in the combined and monotherapy groups, 64.6% and 49.2% had vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and 47.1% had both. In the propensity-score–matched cohort, the OS survival of the combined group was significantly higher compared with the monotherapy group (7.0 months vs. 4.9 months, respectively, P = 0.003). The TTP was significantly longer in the combined group (2.6 months vs. 1.9 months, respectively, P = 0.001). Subgroup analysis showed that the outcomes of patients with advanced HCC without main portal vein invasion who were treated with combined therapy were significantly better compared with those who received monotherapy (P<0.05). Univariate and subsequent multivariate analyses revealed that the addition of sorafenib was an independent predictor of favorable OS and TTP (adjusted hazard ratios, 0.63 and 0.62, respectively; P<0.05 for both).

Conclusion

Sorafenib plus TACE was more effective than TACE monotherapy for treating patients with advanced HCC without main portal vein invasion. Future trials with larger samples are required to validate these preliminary findings.     

Cerebral Lipiodol Embolism in Hepatocellular Carcinoma Patients Treated with Transarterial Embolization/Chemoembolization

Background and Purpose

Liver cancer is the third leading cause of cancer mortality worldwide. The aim of this study was to investigate the frequency and characteristics of cerebral lipiodol embolism (CLE) in patients with hepatocellular carcinoma (HCC) receiving transarterial embolization/chemoembolization (TAE/TACE).

Methods

We reviewed all HCC patients who received TAE/TACE during the period of 2007 and 2013 at a university medical center. The frequency of CLE per procedure and the clinical manifestations of CLE, including the review of previous reported cases (n = 24), were analyzed.

Results

During the study period, a total of 7855 TAE/TACE procedures were conducted on 3277 patients. There were 8 patients (mean age 59±11 years; 5 males and 3 females) who developed CLE. The frequency of TAE/TACE-related CLE was 1.02 (95% CI, 0.44–2.01) per 1000 procedures. Acute disturbance of consciousness and respiratory distress after TAE/TACE were the most common presentations of CLE. All patients had disseminated infarcts involving both the anterior and posterior cerebral circulations. For 3 patients with shunting between the tumor feeding artery and the pulmonary vein, a specific imaging pattern of coexisting scattered hyperdense spots was found. Furthermore, combined with our 8 cases, the total of 32 cases indicated that old age and female sex were the two risk factors for poor outcome after CLE.

Conclusions

CLE is a rare but potentially serious complication in HCC patients receiving TAE/TACE. The clinical characteristics of CLE summarized in our study would help facilitate the ability of clinicians to provide timely diagnosis and management.     

Transarterial Chemoembolization in Combination with Local Therapies for Hepatocellular Carcinoma: A Meta-Analysis

Background

In previous randomized trials, transarterial chemoembolization (TACE) has shown an improvement of survival rate in hepatocellular carcinoma (HCC) when combined with radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) or other therapies. The aim of this meta-analysis was to evaluate the effectiveness of combination therapy of TACE with RFA, PEI, radiotherapy (RT), three-dimensional conformal radiation therapy (3D-CRT) or High-Intensity Focused Ultrasound (HIFU).

Methods

Randomized or nonrandomized studies comparing TACE combined with RFA, PEI, RT, 3D-CRT or HIFU with TACE alone for HCC were included. Meta-analysis was performed using a fix-effects model in RCTs and a random-effects model among the observational studies.

Results

10 randomized trials and 18 observational studies matched the selection criteria, including 2497 patients (682 in RCTs, 1815 in non-RCTs). Meta-analysis of RCTs showed that the combination of TACE and PEI ((RR)_{1 -}year=1.10, 95%CI=0.99-1.22, p=0.073; (RR)_{3 -}year=2.32, 95%CI=1.52-3.53, p<0.001), TACE+RT ((RR)_{1 -}year=1.37, 95%CI=1.11-1.70, p=0.004; (RR)_{3 -}year=2.32, 95%CI=1.44-3.75, p=0.001) were associated with higher survival rates. The results of observational studies were in good consistency with that of RCTs. Furthermore, TACE plus 3D-CRT ((RR)_{1 -}year=1.22, 95%CI=1.06-1.41, p=0.005; (RR)_{3 -}year=2.05, 95%CI=1.48-2.84, p<0.001) and TACE plus HIFU ((RR)_{1 -}year=1.16, 95%CI=1.01-1.33, p=0.033; (RR)_{3 -}year=1.66, 95%CI=1.12-2.45, p=0.011) have introduced marked survival benefit when pooling results from observational studies.

Conclusions

This meta-analysis demonstrated that TACE combined with local treatments, especially PEI, HIFU or 3D-CRT could improve the overall survival status than performing TACE alone. Importantly, these results need to be validated in further high-quality clinical trials.     

Comparison of Long-Term Survival of Patients with Solitary Large Hepatocellular Carcinoma of BCLC Stage A after Liver Resection or Transarterial Chemoembolization: A Propensity Score Analysis

Background

The aim of this study was to compare the long-term outcome of patients with a solitary large (>5 cm) hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage A who received liver resection (LR) or transarterial chemoembolization (TACE).

Methods

Our study examined 128 patients treated by LR and 90 treated by TACE. To reduce bias in patient selection, we conducted propensity score analysis in the present study and 54 pairs of patients after propensity score matching were generated, their long-term survival was compared using the Kaplan–Meier method. Independent predictors of survival were identified by multivariate analysis.

Results

Long-term survival was significantly better for the LR group by log-rank test (P<0.001). In multivariate analysis, tumor size, serum ALT level and TACE independently predicted survival. Despite similar baseline characteristics after propensity score matching, LR group still had significantly better survival (1 year, 68.5 vs. 55.0%; 3 years, 47.6 vs. 21.2%; 5 years, 41.3 vs. 18.5%; P = 0.007) than TACE group. The LR and TACE groups had comparable 30- and 90-day post-treatment mortality. Multivariate analysis showed that serum ALT level, serum AFP level and TACE independently predicted survival by multivariate analysis after propensity score matching.

Conclusion

Our propensity-score-matched study suggested that LR provided significantly better long-term survival than TACE for a solitary large HCC of the BCLC stage A, regardless of tumor size.     

Comparison of Treatment Safety and Patient Survival in Elderly versus Nonelderly Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib Combined with Transarterial Chemoembolization: A Propensity Score Matching Study

AimsThis retrospective study was carried out to compare the outcomes between elderly (≥70 years of age) and nonelderly patients (<70 years of age) with advanced hepatocellular carcinoma (HCC) who received sorafenib combined with transarterial chemoembolization (TACE).Methods88 patients with a confirmed diagnosis of advanced HCC were enrolled in this study. Of these, 24 elderly patients were matched with 48 nonelderly patients at a 1:2 ratio using propensity score matching to minimize selection bias. The related adverse events and survival benefits were compared between the two groups.ResultsSorafenib combined with TACE was equally well tolerated in both age groups, and grade 3 or 4 adverse events were similarly observed in 54.2% of elderly and 50.0% of nonelderly patients (P = 0.739). There were no significant differences in survival time between the elderly and nonelderly patients (P = 0.876). Significant prognostic factors for overall survival as identified by multivariate analysis were the Child–Pugh score and portal vein invasion.ConclusionsSorafenib combined with TACE may be well tolerated and effective in elderly patients with advanced HCC. Age alone is not a parameter for the treatment of advanced HCC patients.     

Comparison of Long-Term Survival of Patients with BCLC Stage B Hepatocellular Carcinoma after Liver Resection or Transarterial Chemoembolization

Background and Aims

Treatment of patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma (BCLC-B HCC) is controversial. This study compared the long-term survival of patients with BCLC-B HCC who received liver resection (LR) or transarterial chemoembolization (TACE).

Methods

A total of 257 and 135 BCLC-B HCC patients undergoing LR and TACE, respectively, were retrospectively evaluated. Kaplan–Meier method was used for long-term survival analysis. Independent prognostic predictors were determined by the Cox proportional hazards model.

Results

The hospital mortality rate was similar between groups (3.1% vs. 3.7%; P = 0.76). However, the LR group showed a significantly higher postoperative complication rate than the TACE group (28 vs. 18.5%; P = 0.04). At the same time, the LR group showed significantly higher overall survival rates (1 year, 84 vs. 69%; 3 years, 59 vs. 29%; 5 years, 37 vs. 14%; P<0.001). Moreover, similar results were observed in the propensity score model. Three independent prognostic factors were associated with worse overall survival: serum AFP level (≥400 ng/ml), serum ALT level, and TACE.

Conclusions

LR appears to be as safe as TACE for patients with BCLC-B HCC, and it provides better long-term overall survival. However, prospective studies are needed to disclose if LR may be regarded as the preferred treatment for these patients as long as liver function is preserved.     

Propensity Score Matching Analysis of Changes in Alpha-Fetoprotein Levels after Combined Radiotherapy and Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

Background and Aim

To investigate the value of changes in alpha-fetoprotein (AFP) levels for the prediction of radiologic response and survival outcomes in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) who received combined treatment of 3-dimensional conformal radiotherapy (3D-CRT) and transarterial chemoembolization (TACE).

Methods

A database of 154 HCC patients with PVTT and elevated AFP levels (>20 ng/mL) treated with 3D-CRT and TACE as an initial treatment between August 2002 and August 2008 was retrospectively reviewed. AFP levels were determined 1 month after radiotherapy, and AFP response was defined as an AFP level reduction of >20% from the initial level. Radiologic response, overall survival (OS), and progression-free survival (PFS) rates were compared between AFP responders and non-responders. Propensity-score based matching analysis was performed to minimize the effect of potential confounding bias.

Results

The median follow-up period was 11.1 months (range, 3.1–82.7 months). In the propensity-score matching cohort (92 pairs), a best radiologic response of CR or PR occurred in more AFP responders than AFP non-responders (41.3% vs. 10.9%, p < 0.001). OS and PFS were also longer in AFP responders than in non-responders (median OS 13.2 months vs. 5.6 months, p < 0.001; median PFS 8.7 months vs. 3.5 months, p < 0.001).

Conclusions

AFP response is a significant predictive factor for radiologic response. Furthermore, AFP response is significant for OS and PFS outcomes. AFP evaluation after combined radiotherapy and TACE appears to be a useful predictor of clinical outcomes in HCC patients with PVTT.     

Association of Serum MicroRNA Expression in Hepatocellular Carcinomas Treated with Transarterial Chemoembolization and Patient Survival

Background and Aim

Hepatocellular carcinoma (HCC) is one of the most deadly tumors. Transarterial chemoembolization (TACE) is effective for unresectable HCC. In recent years, miRNAs have been proposed as novel diagnostic and prognostic tools for HCC. This study aimed to identify whether microRNAs (miRNAs) can serve as biomarkers to reliably predict outcome before HCC patients are treated with TACE.

Methods

Eleven miRNAs (miR-, miR-19a, miR-101-3p, miR-199a-5p, miR-200a, miR-21, miR-214, miR-221, miR-222, miR-223 and miR-, -5p) were quantified by quantitative real-time PCR (qRT-PCR) in 136 HCC patients’ serum before they received TACE therapy. Univariate and multivariate analysis were used to identify the prognostic value of clinical parameters and miRNAs. Area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction potency.

Results

The levels of some miRNAs were dramatically associated with clinicopathologic features regarding Child-Puge class, AFP, tumor size and satellite nodules. Univariate analysis revealed that miR-200a, miR-21, miR-122 and miR-224-5p were significantly associated with patients’ survival. Multivariate analysis demonstrated that AFP, satellite nodules and miR-200a were the independent prognostic factors associated with survival in this cohort (p = 0.000, 0.001, 0.000, respectively). The probability of the prognostic accuracy of miR-200a was 81.64% (74.47% specificity and 88.76% sensitivity), which was higher than the classifier established by combination of AFP and satellite nodules (76.87% probability, 70.21% specificity and 69.66% sensitivity). Furthermore, the combination of AFP, satellite nodules and miR-200a demonstrated as a classifier for HCC prognosis, yielding a ROC curve area of 88.19% (93.62% specificity and 68.54% sensitivity).

Conclusions

Our study indicated that serum miR-200a may prognosticate disease outcome in HCC patients with TACE therapy. Therefore, miR-200a can potentially guide individualized treatment for HCC patients with a high risk of TACE treatment failures.     

Genetic Variants in the EPCAM Gene Is Associated with the Prognosis of Transarterial Chemoembolization Treated Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

The epithelial cell adhesion molecule (EPCAM) is involved in the tumorigenesis and progression of many malignancies, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of EPCAM have been reported to be with the risk and prognosis of several malignancies. However, the association of SNPs in EPCAM gene with the prognosis of HCC patients has never been investigated. In this study, two functional SNPs (rs1126497 and rs1421) in the EPCAM gene were selected and genotyped in a cohort of 448 unresectable Chinese HCC patients treated by TACE. The association of the two SNPs with the overall survival (OS) of patients was assessed by univariate and multivariate Cox proportional hazards model and Kaplan-Meier curve. Our data showed that there was no significant association between either SNP and OS of patients. However, in the stratified analysis, the variant-containing genotypes (WV+VV) of SNP rs1126497 exhibited a significant association with poorer OS in HCC patients who had portal vein tumor thrombus (PVTT) in multivariate analysis of Cox proportional hazard model (hazard ratio, 1.71; 95% confidence interval, 1.16–2.53, P = 0.007), and in Kaplan-Meier curve analysis (P = 0.023), comparing to those carrying wild-type genotype. Our results suggest that SNP rs1126497 in the EPCAM gene may serve as an independent prognosis biomarker for unresectable HCC patient with PVTT, which warranted further validating investigation.     

The Glasgow Prognostic Score Predicts Poor Survival in Cisplatin-Based Treated Patients with Metastatic Nasopharyngeal Carcinoma

Background

Several inflammation-based prognostic scoring systems, including Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have been reported to predict survival in many malignancies, whereas their role in metastatic nasopharyngeal carcinoma (NPC) remains unclear. The aim of this study is to evaluate the clinical value of these prognostic scoring systems in a cohort of cisplatin-based treated patients with metastatic NPC.

Methods

Two hundred and eleven patients with histologically proven metastatic NPC treated with first-line cisplatin-based chemotherapy were retrospectively evaluated. Demographics, disease-related characteristics and relevant laboratory data before treatment were recorded. GPS, NLR and PLR were calculated as described previously. Response to first-line therapy and survival data were also collected. Survival was analyzed in Cox regressions and stability of the models was examined by bootstrap resampling. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of each scoring system.

Results

Among the above three inflammation-based prognostic scoring systems, GPS (P<0.001) and NLR (P = 0.019) were independently associated with overall survival, which showed to be stable in a bootstrap resampling study. The GPS consistently showed a higher AUC value at 6-month (0.805), 12-month (0.705), and 24-month (0.705) in comparison with NLR and PLR. Further analysis of the association of GPS with progression-free survival showed GPS was also associated independently with progression-free survival (P<0.001).

Conclusions

Our study demonstrated that the GPS may be of prognostic value in metastatic NPC patients treated with cisplatin-based palliative chemotherapy and facilitate individualized treatment. However a prospective study to validate this prognostic model is still needed.     

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Survival and Metastasis for Recurrent Hepatocellular Carcinoma after Transarterial Chemoembolization

Purpose

To evaluate whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict survival and metastasis in patients after transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (RHCC).

Materials and Methods

Clinical and laboratory data from 132 RHCC patients treated with TACE from January 2003 to December 2012 were retrospectively reviewed. Prognostic factors were assessed by multivariate analysis, and the predictive values of NLR and PLR for overall survival (OS) and extrahepatic metastases were compared.

Results

Pretreatment mean NLR and PLR were 3.1 and 137, respectively. The 0.5-, 1-, and 2-year OS rates were 93.7%, 67.1%, and 10.1% in the low NLR group and 81.1%, 18.9%, and 3.8% in the high NLR group, respectively (P = 0.017). The corresponding OS rates in the low and high PLR groups were 92.5%, 58.1%, and 9.7% and 84.6%, 23.1%, and 2.6%, respectively (P = 0.030). The discriminatory performance predicting 1-year survival probability was significantly poorer for NLR (area under the curve [AUC] = 0.685, 95% confidence interval [CI] 0.598–0.763) than for PLR (AUC = 0.792, 95% CI 0.712–0.857; P = 0.0295), but was good for both ratios for predicting post-TACE extrahepatic metastasis. Multivariate analysis indicated that high PLR (hazard ratio [HR] = 0.373, 95% CI = 0.216-0.644, P < 0.001, vascular invasion (HR = 0.507, 95% CI = 0.310–0.832, P = 0.007), and multiple tumors (HR= 0.553, 95% CI = 0.333–0.919, P = 0.022) were independent prognostic factors for OS.

Conclusions

High NLR and PLR were both associated with poor prognosis and metastasis in RHCC patients treated with TACE, but high PLR was a better predictor of 1-year OS. High PLR, vascular invasion, and multiple tumors were independent, unfavorable prognostic factors.     

Increased Circulating Th17 Cells after Transarterial Chemoembolization Correlate with Improved Survival in Stage III Hepatocellular Carcinoma: A Prospective Study

Transarterial chemoembolization (TACE) has therapeutic effects in patients with unresectable hepatocellular carcinoma (HCC), but its impact on the cellular immune response during disease progression is largely unknown. Here we conducted a prospective study to evaluate the effect of TACE on immune status and to identify prognostic immune markers governing treatment success. In this study, 51 stage III HCC patients, 28 stage I HCC patients (TNM classification) and 20 healthy donors were enrolled. Flow cytometry and cytometric bead array were used to evaluate the circulating immune cell subsets, including CD4⁺ T cells (Th1, Th17 and Treg cells), CD8⁺ T cells, NK cells, and NKT cells, and plasma cytokines before TACE and 30 days after TACE. Interestingly, among those immune parameters, the frequency of circulating Th17 cells was higher in stage III HCC patients than in stage I HCC patients (P = 0.015) and healthy donors (P<0.001). Moreover, an increased frequency of circulating Th17 cells was observed 30 days after TACE (Th17_D30) compared with the baseline level (P = 0.036). Kaplan-Meier analysis demonstrated that Th17_D30 was positively associated with overall survival (OS; P = 0.007) and time to progression (TTP; P = 0.009). Multivariate Cox analysis revealed that Th17_D30 was an independent prognostic factor for OS (HR = 0.317, P = 0.032) and TTP (HR = 0.304, P = 0.010). These results provide a potential prognostic marker for stage III HCC patients undergoing TACE and may be useful for identifying patients who can benefit from adjuvant immunotherapies.     

Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma

BackgroundPrognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC.ConclusionsThe ITA.LI.CA prognostic system includes both a tumor staging—stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)—and a prognostic score—integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations.     

肝细胞癌根治性切除术后预后因素分析

目的:探讨影响肝细胞癌患者根治性术后预后相关因素。方法:回顾性分析2004年1月1日至2009年12月31日245例我院行根治性切除术的肝细胞癌患者,采用Kaplan-Meier法和Cox比例风险模型分析临床资料、手术过程、病理特征与预后的关系。结果:多因素分析结果显示术前AFP水平、术中出血量、TNM分期是影响无进展生存时间和总生存时间的独立风险因素。术前AFP水平越高、术中出血量越大、TNM分期越晚则患者无进展生存时间及总生存时间明显缩短。此外,患者出现肿瘤组织局部坏死、门静脉癌栓,则总生存时间明显缩短。结论:术前AFP水平、术中出血量、TNM分期是外科根治性切除术后肝细胞癌患者复发及死亡的相关因素,对于临床医师判断预后及延长术后生存时间具有重要的临床意义。     

Modifiable Prognostic Factors of Hepatocellular Carcinoma in Patients with Non-Surgical Treatment

Background & aims

Current hepatocellular carcinoma (HCC) staging systems only use baseline characteristics to predict outcome. We aimed to explore modifiable factors of the prognosis in HCC cases had undergone non-surgical treatment.

Methods

All HCC cases in Kaohsiung Chang Gung Memorial hospital in southern Taiwan from 2002 to 2012 must met all below criteria: (1) met international diagnostic guidelines, (2) underwent the initial treatments in our hospital (3) treated by non-surgical treatment modalities and (4) survived more than two years, with follow-up time longer than five years.

Results

A total 698 patients were enrolled: 451 (24.6%, group A) survivied between 2 to 5 years, and 247 (13.5%, group B) had survived > 5 years. Aside from liver function reserve and BCLC stages, four interventional factors: initial treatment modality, outcomes of 1^st or 2^nd treatment, and anti-viral therapy to chronic viral hepatitis were associated with prognosis. After propensity score matching, multiple logistic regression of 223 well-matched pairs showed that recurrence within one year after 1^st treatment (OR: 2.17, 95% CI: 1.35–3.48), incomplete 2^nd treatment (2.01, 1.27–3.17) and absence of anti-viral agents (1.68, 1.09–2.59) were independent poor prognostic factors.

Conclusion

Complete treatment and anti-viral agents to chronic hepatitis were both independent modifiable prognostic factors of HCC patients had undergone non-surgical treatment. Based on these findings, timely treatment to achieve maximal locoregional control and anti-viral treatment should be provided as possible.     

Meta-Analysis: Prognostic Value of Survivin in Patients with Hepatocellular Carcinoma

Background

The expression of survivin is a promising prognostic indicator for some carcinomas. However, evidence for the prognostic value of survivin with respect to survival in hepatocellular carcinoma remains controversial.

Aim

To conduct a systematic review of studies evaluating survivin expression in hepatocellular carcinoma as a prognostic indicator.

Methods

The relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases, and two meta-analyses were performed. One studied the association between survivin expression and the overall survival of patients with hepatocellular carcinoma, whereas the other studied the association between survivin expression and disease-free survival. Studies were pooled, and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted.

Results

Fourteen eligible studies with a total of 890 patients were included in this study. Two meta-analyses were performed according to the different outcomes by which prognosis was valued. The combined HR of the overall survival studies was 2.33 (95% CI: 1.65–3.31). The combined HR of disease-free survival studies was 2.13 (95% CI: 1.65–2.75). These data appeared to be significant when stratified by detection method, the language of publication, and HR estimate. The heterogeneities were highly significant (I²>50%) when subgroup analyses of overall survival rate were conducted, whereas little heterogeneity was found when subgroup analyses of disease-free survival rate were carried out. The positive expression of survivin in the cytoplasm was significantly correlated with poor prognosis in HCC (HR>1).

Conclusions

This study showed that survivin expression was correlated with poor prognosis in patients with hepatocellular carcinoma, regardless whether they were assessed by overall survival or disease-free survival.     

A New Therapeutic Assessment Score for Advanced Hepatocellular Carcinoma Patients Receiving Hepatic Arterial Infusion Chemotherapy

MethodsWe retrospectively analyzed 90 advanced HCC patients with elevated baseline alpha-fetoprotein (AFP) and/or des-gamma-carboxy prothrombin (DCP) levels and analyzed various parameters for their possible use as predictors of response and survival. AFP and DCP responses were assessed after half a course of HAIC (2 weeks); a positive-response was defined as a reduction of ≥ 20% from baseline.ResultsMultivariate analysis identified DCP response (odds ratio 16.03, p < 0.001) as an independent predictor of treatment response. In multivariate analysis, Child-Pugh class A (hazard ratio [HR] 1.99, p = 0.018), AFP response (HR 2.17, p = 0.007), and DCP response (HR 1.90, p = 0.030) were independent prognostic predictors. We developed an Assessment for Continuous Treatment with HAIC (ACTH) score, including the above 3 factors, which ranged from 0 to 3. Patients stratified into two groups according to this score showed significantly different prognoses (≤1 vs. ≥2 points: median survival time, 15.1 vs. 8.7 months; p = 0.003).ConclusionsThe ACTH score may be useful in the therapeutic assessment of HCC patients receiving HAIC.     

Serum miR-128-2 Serves as a Prognostic Marker for Patients with Hepatocellular Carcinoma

Circulating miRNAs are promising biomarkers for predicting the aggressiveness of hepatocellular carcinoma (HCC). We aimed to identify differentially expressed miRNAs in the serum of HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stage, and to investigate the potential of serum miRNAs as biomarkers for patient outcomes. In the discovery stage, TaqMan Low-Density Array was used to test the difference in levels of serum miRNAs between 20 patients with portal vein tumor thrombosis (PVTT) and 20 patients without PVTT. The detected serum miRNAs then were validated in 182 patients. Fifteen serum miRNAs showed more than two-fold higher expression in patients with PVTT, and miR-128-2 was found to be significantly up-regulated and was selected for further validation. In the validation stage, patients were divided into two groups with low or high serum miR-128-2 using the median expression level of all 182 cases as the cut-off point. Kaplan-Meier analysis revealed that patients with low level of serum miR-128-2 had favorable trends of survival (log rank = 13.031, p < 0.001). The median survivals for patients with a low and high level of serum miR-128-2 were 625 (95% CI, 527–722) days and 426 (95% CI, 362–491) days, respectively. MiR-128-2 was also an independent factor of overall survival (p = 0.001, HR 2.793, 95%CI 1.550, 5.033). Serum levels of the ubiquitously expressed miR-128-2 showed no significant correlation with parameters of liver damage or liver function. In addition, expressions of miR-128-2 in HCC tissues were up-regulated in comparison with adjacent non-tumor tissues. In conclusion, serum level of miR-128-2 serves as a noninvasive biomarker for the overall survival of patients with hepatocellular carcinoma.     

Batimastat Nanoparticles Associated with Transcatheter Arterial Chemoembolization Decrease Hepatocellular Carcinoma Recurrence

Hepatocellular carcinoma (HCC) is a malignant tumor characterized by easy metastasis and frequent recurrence. Transarterial chemoembolization (TACE) remains the routine treatment for patients with HCC who are not eligible for surgical resection or percutaneous tumor ablation; however, 5-year survival rates following interventional therapy are only 17–38.8 %, with liver recurrence due to incomplete embolization and tumor angiogenesis being a significant reason for treatment failure. Ischemia and hypoxia induced by TACE is correlated with an increased expression of angiogenic factor and stimulates an increase in angiogenesis, including endothelial cells (ECs) proliferation. Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic endopeptidases involved in tumor angiogenesis. In addition, MMPs stimulate tumor cell growth, migration and invasion, and metastasis. Hypoxia enhanced EC migration in a MMP-2-dependent manner while MMP inhibitors (MMPIs) significantly decreased the number of migrating cells in hypoxic cultures. We hypothesize batimastat (synthetic MMPI) nanoparticles associated with TACE could decrease HCC recurrence and metastasis. At first, batimastat nanoparticles were made from batimastat and poly(lactic-co-glycolic acid). Then, nanoparticles were mixed with lipiodol and chemotherapeutic drugs solution. The mixture was infused super-selectively into supplied artery of HCC through catheter. The disseminated area of batimastat might be same with TACE-induced hypoxia area. In the hypoxia area, batimastat inhibited the activity of MMPs, weakened the angiogenesis of tumor vascular system and migration of HCC cells. HCC cells could not escape from hypoxia area and tumor angiogenesis inhibited could not supply sufficient nutrients and O₂ to residual HCC cells. With the help of batimastat, the killing effect of chemotherapeutic drugs might be enhanced. The rate of complete necrosis of HCC lesion might be increased and local recurrence and metastasis of HCC might be reduced. The hypothesis might increase the clinical efficacy of TACE and improve the prognosis of HCC patients.     

肝动脉栓塞化疗术对原发性肝癌伴 有不同类型肝炎后肝硬化患者预后的影响

目的:探讨肝动脉栓塞化疗(TACE)对原发性肝癌伴有不同肝炎后肝硬化类型患者术后肝功能、凝血功能及其对远期预后的影响。方法:2007年8月至2009年8月,131例曾行TACE的伴有不同肝炎后肝硬化原发性肝癌患者,以肝炎后肝硬化类别(乙肝、丙肝)分类,乙肝后肝硬化组为组1,丙肝后肝硬化组为组2,随访观察术后一年肝功能、凝血功能、血小板等的变化以及预后。两组研究因素采用SPSS17.0进行卡方检验,随访预后采用Kaplan-Meier方法计算生存率,Log-rank法检验生存差异。以P<0.05为差异有统计学意义。结果:随访统计结果显示术后半年和一年AST、ALT、ALP、GGT、PT、PLT在两组间均无统计学差异,(P>0.05);组一半年、一年远处转移率同组二差异间无统计学意义;组一半年、一年生存率分别为70.1%,48.1%;组二半年、一年生存率分别为68.5%,58.9%,两组间同期生存率差异无统计学意义。(X2=0.039,P=0.884;X2=0.183,P=0.669)。结论:TACE治疗PHC安全可靠,对于伴有乙肝或丙肝后肝硬化患者术后肝功能、凝血功能、疗效及预后效果相当。