Chemoembolization alone vs combined chemoembolization and hepatic arterial infusion chemotherapy in inoperable hepatocellular carcinoma patients

AIM: To compare the efficacy and safety of chemoem-bolization alone or chemoembolization combined with hepatic arterial infusion chemotherapy(HAIC),including oxaliplatin(OXA),5-fluorouracil(5-FU) and folinic acid(CF),in inoperable hepatocellular carcinoma(HCC) without distant metastasis. METHODS: Eighty-four inoperable HCC patients were enrolled. Thirty-ninepatient sunderwent chemoembolization alone,and the other 45 patients underwent chemoembolization + HAIC(OXA/5-FU/CF) treatment non-randomly. The progression free survival(PFS),objective response rate(ORR),disease control rate(DCR) and adverse reactions were compared between the two groups.RESULTS: A significant difference in the ORR was observed between the chemoembolization alone and chemoembolization + HAIC groups. There was no statistically significant difference in DCR between the two groups. The median PFS(m PFS) showed a significant difference between the two groups. For patients with BCLC stage A/B disease,with or without vessel invasion,the chemoembolization + HAIC group showed better m PFS when compared to chemoembolization alone,but no significant difference was found in patients with BCLC stage C disease. The parameter of pain(grade Ⅲ-Ⅳ) in the chemoembolization + HAIC group was increased statistically. CONCLUSION: Chemoembolization combined with HAIC with OXA/5-FU/CF may be safe and more effective than chemoembolization alone for inoperable HCC patients without distant metastasis.

Impact of Serum Vascular Endothelial Growth Factor on Prognosis in Patients with Unresectable Hepatocellular Carcinoma after Transarterial Chemoembolization

Objective： To investigate the expression level with unresectable hepatocellular carcinoma （HCC） and to assess the impact of serum VEGF as chemoembolization （TACE） treatments. of serum vascular endothelial growth factor （VEGF） in patients and its relationship with the c a predictive factor for HCC nicopathological characteristics, prognosis during transarterial Methods： Serum VEGF levels were measured using enzyme-linked immunosorbent assay （ELISA） in 60 random patients who underwent TACE or transarterial infusion （TAI） for unresectable HCC between May and September 2008 and 12 healthy volunteers were also involved in this study to serve as control. All patients＇ clinicopathological features were retrospectively analyzed. Serum VEGF levels were correlated with clinicopathological features of the HCC patients. The patients＇ survival rates were analyzed with Kaplan-Meier survival curves and compared by the log-rank test. The prognostic significance of serum VEGF levels and factors related to survival rate were evaluated by univariate and multivariate analysis. Results： The median serum VEGF level in the HCC patients was 285 pg/ml （range 14-1,207 pg/ml）, significantly higher than that of healthy controls （P=0.021）. The serum VEGF levels were significantly correlated with platelet counts （r=0.396, P=0.002） but not other clinicopathological features. Patients with serum VEGF level 〉285 pg/ml had worse overall survival compared with those with serum VEGF level 〈285 pg/ml （P=0.002）. By multivariate analysis, the serum VEGF level was a significant prognostic factor. Conclusion： High serum VEGF levels may predict poor prognosis of HCC after TACE. This study highlights the importance of tumor biomarker as a prognostic predictor in TACE therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.

Sorafenib combined with embolization plus hepatic arterial infusion chemotherapy for inoperable hepatocellular carcinoma

BACKGROUND There is little evidence of combining sorafenib with hepatic arterial infusion chemotherapy(HAIC)after transarterial chemoembolization(TACE)for intermediate and advanced hepatocellular carcinoma(HCC).It is important to identify that patients with intermediate and advanced HCC are most likely to benefit from this combination therapy.AIM To investigate the safety and clinical outcomes of sorafenib combined with HAIC with folinic acid,5-fluorouracil(5-FU),and oxaliplatin(FOLFOX)after TACE for intermediate and advanced HCC.METHODS This prospective phase II study enrolled patients with intermediate and advanced HCC who underwent treatment with sorafenib combined with TACEHAIC.All patients initially received the standard 400 mg dose of sorafenib twice daily before TACE-HAIC.Participants at our institute with intermediate and advanced HCC underwent routine TACE.Then,the catheter used for embolization was kept in place in the hepatic artery,and oxaliplatin was intraarterially administered for 6 h,followed by 5-FU for 18 h,and folinic acid was intravenously administered for 2 h.The primary endpoints were safety,as evaluated by the Common Terminology and Criteria for Adverse Events version 4.0,and 12-mo progression-free survival(PFS),as analyzed by the Kaplan-Meier method.As secondary endpoints,the objective response rate(ORR)was evaluated by the modified Response Evaluation Criteria for Solid Tumors,and survival time[overall survival(OS)]was analyzed by the Kaplan-Meier method.RESULTS Sixty-six participants at our institute with intermediate and advanced HCC were enrolled in this prospective study(mean age,53.3±11.7 years).Approximately 56.1%of participants had Barcelona Clinic Liver Cancer(BCLC)stage C disease,and 43.9%had BCLC stage B disease.The ORR was 42.4%.The disease control rate was 87.9%.The grade 3-4 toxicities consisted of thrombocytopenia(4.5%),neutropenia(3.0%),and elevated aspartate aminotransferase(12.2%).Hand-foot skin reaction was also observed(40.9%).The median PFS was 13.1 mo(13.5 mo in the BCLC stage B participants and 9.4 mo in the BCLC stage C participants).The 6-mo,12-mo,and 24-mo PFS rates were 75.0%,54.7%,and 30.0%,respectively.The median OS was 21.8 mo.CONCLUSION Sorafenib combined with HAIC(FOLFOX)after TACE may be a feasible treatment choice for intermediate and advanced HCC because this treatment met the prespecified endpoint of a 6-mo PFS rate exceeding 50%and had good patient tolerance.Prospective randomized controlled trials are needed to confirm the effect of this combination therapy.

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)and hepatic arterial infusion chemotherapy(HAIC)have shown promising local benefits for advanced hepatocellular carcinoma(HCC).S-1,a composite preparation of a 5-fluorouracil prodrug,has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC.AIM To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC.METHODS In this single-center,open-label,prospective,randomized controlled trial,117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with(TACE/HAIC+S-1,n=56)or without(TACE/HAIC,n=61)oral S-1 between December 2013 and September 2017.Two participants were excluded from final analysis for withdrawing consent.The primary endpoint was progression-free survival(PFS)and secondary endpoints included overall survival(OS),objective response rate,disease control rate and safety.RESULTS In total,115 participants(100 males and 15 females;mean age,57.7 years±11.9)were analyzed.The median PFS and OS were 5.0 mo(0.4–58.6 mo)(95%confidence interval(CI):3.82 to 6.18)vs 4.4 mo(1.1–54.4 mo)(95%CI:2.54 to 6.26;P=0.585)and 8.4 mo(0.4–58.6 mo)(95%CI:6.88 to 9.92)vs 8.3 mo(1.4–54.4 m)(95%CI:5.71 to 10.96;P=0.985)in the TACE/HAIC+S-1 and TACE/HAIC groups,respectively.The objective response rate and disease control rate were 30.9%vs 18.4%and 72.7%vs 56.7%in the TACE/HAIC+S-1 and TACE/HAIC groups,respectively.Grade 3/4 adverse events had a similar frequency in both treatment groups.CONCLUSION No improvements in tumor response rates,PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC.Both treatment regimens had a similar safety profile.

Hepatocellular Carcinoma with Blood Supply from Parasitized Omental Artery: Angiographic Appearance And Chemoembolization

Objective： To analyze angiographic appearance of hepatocellular carcinoma （HCC） with blood supply from parasitized omental artery （POA）, and evaluate the technical feasibility, safety and therapeutic efficacy of chemo-embolization via the POAs. Methods： A total of 1,221 HCC patients who had undergone chemoembolization procedures were evaluated retrospectively. The evaluated indexes included the incidence rate of POAs, success rate of superselective catheterization, post-reaction after chemoembolization, and the cumulative survival rates. Results： Totally 1,221 HCC patients had undergone 3,639 chemoembolization procedures, and 32 patients with POAs were enrolled, with 97 POAs found in 76 angiography procedures, giving an incidence rate of 2.09%. POA was observed mostly at the right lobe and left medial lobe except the segment II, and 62 POAs underwent superselective catheterization with microcatheter, giving a success rate of 63.9%. The angiographic appearance was： （1） hypertrophic POAs participating in tumor staining （n=28）; （2） stiff and distorted POA （n=11）, displaced due to tumor＇s oppression （n=8）; and （3） defective tumor staining close to either gastrocolic omentum distribution or liver capsule （n=7）. In 19 patients, chemoembolization via POAs was performed successfully （A group）, while the remaining 13 patients failed （B group）. Except 1 acute edema pancreatitis case, no serious complication was recorded. The cumulative survival rates of 6-, 12-, 18- and 24-month were 78.9%, 47.4%, 31.6% and 21.1% respectively for A group; correspondingly, 61.5%, 30.8%, 15.4% and 7.7%% for B group, in which 2 patients died of ruptured HCC. Conclusion： Chemoembolization with microcatheter via POAs is a relatively safe, feasible and valuable method.

Effect of primary tumor side on survival outcomes in metastatic colorectal cancer patients after hepatic arterial infusion chemotherapy

AIM To analyze the survival data between patients diagnosed with right-sided primary(RSP) tumors and patients diagnosed with left-sided primary(LSP) tumors after hepatic arterial infusion chemotherapy(HAIC) at our center.METHODS A retrospective analysis of pretreated metastatic colorectal cancer patients who received HAIC from May 2006 to August 2015 was conducted. A Cox proportional hazard regression analysis was used to assess the long-term survival outcomes. The mean and median age of patients was 61 years(range 27-85 years). There were 115 males and 53 females in our study.RESULTS One hundred sixty-eight patients were enrolled in this study. The overall response rate was 28.9% in LSP patients and 27.3% in RSP patients. The disease control rate was 76.3% in LSP patients and 69.7% in RSP patients. The median overall survival in response to HAIC was 16.3 mo in the LSP arm and 9.3 mo in the RSP arm(P = 0.164). The median progression-free survival was 5.7 mo in the LSP arm and 4.2 mo in the RSP arm(P = 0.851).CONCLUSION There was no significant difference in survival between LSP patients and RSP patients after HAIC. Further prospective studies are needed to confirm these findings.

An Oncolytic Adenovirus Expressing Herpes Simplex Virus-Thymidine Kinase for Targeting Cancer Therapy:An in vitro Evaluation

Objective： Oncolytic adenovirus, also called conditionally replicating adenovirus （CRAD）, has been developed for the treatment of cancer. However, there is a tremendous need to enhance their antitumor efficacy. Here we wish to evaluate whether a strategy that combines the herpes simplex virus-thymidine kinase with oncolytic effects offers a therapeutic advantage. Methods： A novel adenovirus Ad-ETK containing a sequentially positioned promoter of human telomerase reverse transcriptase （hTERT）, the coding sequence of E1A gene, an internal ribosome entry site sequence （IRES） and the coding sequence of herpes simplex virus-thymidine kinase （HSV-TK） was constructed. Infection of various cells with Ad-ETK followed by RT-PCR confirmed the expression of E1A and HSV-TK. The oncolytic ability and synergism between oncolytic effects and HSV-TK system was measured. The infection efficiency was determined by flow cytometry. Results： Ad-ETK deliverys E1A and HSV-TK gene, which selectively replicates in hTERT-positive tumor cells, and the progeny virus can reach up to 150 IU/cell. Our in vitro study showed that Ad-ETK plus ganciclovir （GCV） induced an obvious cell death. Conclusion： An oncolytic adenovirus plus the HSV-TK/GCV suicide gene system resulted in a significant improvement in treatment efficacy and it may offer important considerations in the development and preclinical assessments of oncolytic virotherapy.

Coronary plaque property evaluation by coronary CTA and its correlation with inflammatory molecules and MMPs/TIMPs

Objective: To study the evaluation value of coronary CTA for coronary plaque properties and its correlation with inflammatory molecules and MMPs/TIMPs. Methods: Patients who were diagnosed with acute coronary syndrome in Renmin Hospital of Wuhan University between August 2014 and December 2016 were selected as the ACS group of the research, patients who were diagnosed with stable angina pectoris were selected as the SAP group of the research, and healthy subjects who received physical examination during the same period were selected as the control group of the research. Coronary CTA was done to determine the coronary plaque properties of ACS group, and serum was collected from the three groups of subjects to determine the contents of inflammatory molecules and MMPs/TIMPs collagen metabolites. Results: Serum MIP-1 , MCP-1, sFGL-2, sCD14, CXCL5, I-CTP, III-CTP and EMMPRIN contents of ACS group and SAP group were higher than those of control group while TIMP1, TIMP2 contents were lower than those of control group;serum MIP-1 , MCP-1, sFGL-2, sCD14, CXCL5, Ⅰ-CTP, Ⅲ-CTP and EMMPRIN contents of ACS group were higher than those of SAP group while TIMP1 and TIMP2 contents were lower than those of SAP group. Serum MIP-1 , MCP-1, sFGL-2, sCD14, CXCL5, Ⅰ-CTP, Ⅲ-CTP and EMMPRIN contents of ACS patients with soft plaque and fibrous plaque were higher than those of ACS patients with calcified plaque while TIMP1 and TIMP2 contents were lower than those of ACS patients with calcified plaque;serum MIP-1 , MCP-1, sFGL-2, sCD14, CXCL5, Ⅰ-CTP, Ⅲ-CTP and EMMPRIN contents of ACS patients with soft plaque were higher than those of ACS patients with fibrous plaque while TIMP1, TIMP2 contents were lower than those of ACS patients with fibrous plaque. Conclusion: The coronary plaque property evaluation by coronary CTA is closely related to the changes of inflammatory response and MMPs/TIMPs collagen metabolism.

Impact of metabolic syndrome on short-term outcome of carotid revascularization: a large sample size study in Chinese population

Background:Metabolic syndrome(MetS)is relatively common worldwide and an important risk factor for cardiovascular diseases.It is closely linked to arterial stiffness of the carotid artery.However,the association of MetS with the safety of carotid revascularization has been rarely studied.The aim of this study was to observe the current status of MetS and its components in Chinese carotid revascularized patients,and investigate the impact on major adverse clinical events(MACEs)after carotid endarterectomy(CEA)or carotid artery stenting(CAS).Methods:From January 2013 to December 2017,patients undergoing CEA or CAS in the Neurosurgery Department of Xuanwu Hospital were retrospectively recruited.The changes in prevalence of MetS and each component with time were investigated.The primary outcome was 30-day post-operative MACEs.Univariable and multivariable analyses were performed to identify the impact of MetS on CEA or CAS.Results:A total of 2068 patients who underwent CEA(766 cases)or CAS(1302 cases)were included.The rate of MetS was 17.9%;the prevalence rate of MetS increased with time.The occurrence rate of MACEs in CEA was 3.4%(26 cases)and in CAS,3.1%(40 cases).There was no statistical difference between the two groups(3.4%vs.3.1%,P=0.600).For CEA patients,univariate analysis showed that the MACE(+)group had increased diabetes history(53.8%vs.30.9%,P=0.014)and MetS(34.6%vs.15.8%,P=0.023).For CAS patients,univariate analysis showed that the MACE(+)group had increased coronary artery disease history(40.0%vs.21.6%,P=0.006)and internal carotid artery tortuosity(67.5%%vs.37.6%,P<0.001).Furthermore,the MACE(+)group had higher systolic blood pressure(143.38±22.74 vs.135.42±17.17 mmHg,P=0.004).Multivariable analysis showed that the influencing factors for MACEs in CEA included history of diabetes(odds ratio[OR]=2.345;95%confidence interval[CI]=1.057-5.205;P=0.036)and MetS(OR=2.476;95%CI=1.065-5.757;P=0.035).The influencing factors for MACEs in CAS included systolic blood pressure(OR=1.023;95%CI=1.005-1.040;P=0.010),coronary artery disease(OR=2.382;95%CI=1.237-4.587;P=0.009)and internal carotid artery tortuosity(OR=3.221;95%CI=1.637-6.337;P=0.001).Conclusions:The prevalence rate of MetS increased with time in carotid revascularized patients.MetS is a risk for short-term MACEs after CEA,but not CAS.