The incidence of hepatocellular carcinoma(HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplan...The incidence of hepatocellular carcinoma(HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization(TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients' presentations, a multidisciplinaryteam should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved moleculartargeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.展开更多
AIM: To asses the value of computed tomography (CT)-perfusion in the detection of residual hepatocellular carcinoma (HCC) vascularization after transarterial chemoembolization (TACE). METHODS: Thirty-two consecutive p...AIM: To asses the value of computed tomography (CT)-perfusion in the detection of residual hepatocellular carcinoma (HCC) vascularization after transarterial chemoembolization (TACE). METHODS: Thirty-two consecutive patients were pro-spectively included in this study. All patients had liver cirrhosis and a conf irmed HCC lesion which was treated with TACE. One month after treatment, perfusion measurements of treated lesions were carried out. The CTperfusion (CT-p) protocol was performed with 16 slice multidetector computed tomography which included the following parameters: 8 dynamic slices/scan per 40 scans after iv injection of 50 mL of iodinated contrast (350 mg/mL) at a flow rate of 6 mL/s. Treated lesions were evaluated using dedicated perfusion software, which generated a quantitative colour map of perfusion. The following parameters were considered: hepatic perfusion (HP), arterial perfusion (AP), blood volume (BV), hepatic perfusion index (HPI), and time to peak (TTP). Perfusion parameters were described with quartile values of their distribution and statistically analyzed. RESULTS: Perfusion parameters of the treated lesions could be quantitatively assessed using CT-p analysis. The presence of residual tumor tissue was observed in 13 of the 32 patients. The values of the perfusion parameters measured within the relapse tissue were: HP (mL/100 g per minute): median = 44.4 (1stqt = 31.3, 3rdqt = 55.8); BV (mL/100 g): median = 18.7 (1stqt = 11.5, 3rdqt = 22.5); AP (mL/min): median = 39.0 (1stqt = 36.5, 3rdqt = 61.3); HPI (%): median = 34.0 (1stqt = 30.4, 3rdqt = 38.9); TTP (s): median = 17.3 (1stqt = 15.8, 3rdqt = 26.5). With the use of the univariate paired Wilcoxon signed rank test, HP, AP and HPI were shown to be significantly higher (P<0.001) in the relapse site than in the primary lesion. The BV and TTP parameters showed a tendency to be greater and lower, respectively, in the relapse site than in the primary lesion. CONCLUSION: In patients with HCC treated with TACE, CT-p provides measurement of flow 展开更多
目的探讨TACE术后肿瘤微环境的T细胞表型、PD-1(程序性细胞死亡受体)及其配体PD-L1和免疫抑制相关蛋白CD73表达变化及其在预测预后中的价值。方法本研究收集了20例2019年5月到2020年12月间经TACE治疗后转化切除的肝癌组织样本(TACE组,简...目的探讨TACE术后肿瘤微环境的T细胞表型、PD-1(程序性细胞死亡受体)及其配体PD-L1和免疫抑制相关蛋白CD73表达变化及其在预测预后中的价值。方法本研究收集了20例2019年5月到2020年12月间经TACE治疗后转化切除的肝癌组织样本(TACE组,简称T+组),同时收集20例同期未接受过TACE治疗的肝癌组织样本作为对照组(无TACE组,简称T-组)。通过对肿瘤组织切片进行多重荧光免疫组化,比较两组患者肿瘤内(FOXP3^(+))调节性T细胞(Treg)、免疫耗竭的(CD8^(+)/PD-1^(+))T细胞数量及PD-L1和CD73的表达情况。统计分析不同的T细胞表型及CD73表达水平对患者无进展生存期的影响,并通过Cox多因素回归分析影响患者预后的主要因素。结果T+组中的肿瘤组织中的CD73表达水平明显高于T-组(11.86 vs 7.7,P=0.047)。T+组的Treg、CD8^(+)和CD8^(+)PD-1^(+)T细胞数量分别为35.93、86.09、13.91,明显低于T-组的60.02(P=0.013)、120.27(P=0.043)和28.36(P=0.015),而PD-L1表达水平在T+与T-中无明显差异(23.68 vs 21.04,P=0.380)。CD73高表达组显示更少的CD8^(+)(84.83 vs 121.53,P=0.029)和CD8^(+)PD-1^(+)(15.00 vs 27.27,P=0.041)T细胞数量,FOXP3^(+)数量两组无差异(45.50 vs 50.45,P=0.623)。Kaplan-Meier生存分析显示,CD73高表达以及CD8^(+)PD-1^(+)高表达患者的无进展生存期更差(P值分别为0.009和0.019)。结论TACE术后肿瘤免疫微环境CD73表达升高,而FOXP3^(+)和CD8^(+)/PD-1^(+)T细胞数量降低,而CD73高表达以及CD8^(+)PD-1^(+)高表达与患者不良预后密切相关,提示靶向CD73可能会成为TACE联合治疗的新方向。展开更多
文摘The incidence of hepatocellular carcinoma(HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization(TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients' presentations, a multidisciplinaryteam should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved moleculartargeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.
文摘AIM: To asses the value of computed tomography (CT)-perfusion in the detection of residual hepatocellular carcinoma (HCC) vascularization after transarterial chemoembolization (TACE). METHODS: Thirty-two consecutive patients were pro-spectively included in this study. All patients had liver cirrhosis and a conf irmed HCC lesion which was treated with TACE. One month after treatment, perfusion measurements of treated lesions were carried out. The CTperfusion (CT-p) protocol was performed with 16 slice multidetector computed tomography which included the following parameters: 8 dynamic slices/scan per 40 scans after iv injection of 50 mL of iodinated contrast (350 mg/mL) at a flow rate of 6 mL/s. Treated lesions were evaluated using dedicated perfusion software, which generated a quantitative colour map of perfusion. The following parameters were considered: hepatic perfusion (HP), arterial perfusion (AP), blood volume (BV), hepatic perfusion index (HPI), and time to peak (TTP). Perfusion parameters were described with quartile values of their distribution and statistically analyzed. RESULTS: Perfusion parameters of the treated lesions could be quantitatively assessed using CT-p analysis. The presence of residual tumor tissue was observed in 13 of the 32 patients. The values of the perfusion parameters measured within the relapse tissue were: HP (mL/100 g per minute): median = 44.4 (1stqt = 31.3, 3rdqt = 55.8); BV (mL/100 g): median = 18.7 (1stqt = 11.5, 3rdqt = 22.5); AP (mL/min): median = 39.0 (1stqt = 36.5, 3rdqt = 61.3); HPI (%): median = 34.0 (1stqt = 30.4, 3rdqt = 38.9); TTP (s): median = 17.3 (1stqt = 15.8, 3rdqt = 26.5). With the use of the univariate paired Wilcoxon signed rank test, HP, AP and HPI were shown to be significantly higher (P<0.001) in the relapse site than in the primary lesion. The BV and TTP parameters showed a tendency to be greater and lower, respectively, in the relapse site than in the primary lesion. CONCLUSION: In patients with HCC treated with TACE, CT-p provides measurement of flow
文摘目的探讨TACE术后肿瘤微环境的T细胞表型、PD-1(程序性细胞死亡受体)及其配体PD-L1和免疫抑制相关蛋白CD73表达变化及其在预测预后中的价值。方法本研究收集了20例2019年5月到2020年12月间经TACE治疗后转化切除的肝癌组织样本(TACE组,简称T+组),同时收集20例同期未接受过TACE治疗的肝癌组织样本作为对照组(无TACE组,简称T-组)。通过对肿瘤组织切片进行多重荧光免疫组化,比较两组患者肿瘤内(FOXP3^(+))调节性T细胞(Treg)、免疫耗竭的(CD8^(+)/PD-1^(+))T细胞数量及PD-L1和CD73的表达情况。统计分析不同的T细胞表型及CD73表达水平对患者无进展生存期的影响,并通过Cox多因素回归分析影响患者预后的主要因素。结果T+组中的肿瘤组织中的CD73表达水平明显高于T-组(11.86 vs 7.7,P=0.047)。T+组的Treg、CD8^(+)和CD8^(+)PD-1^(+)T细胞数量分别为35.93、86.09、13.91,明显低于T-组的60.02(P=0.013)、120.27(P=0.043)和28.36(P=0.015),而PD-L1表达水平在T+与T-中无明显差异(23.68 vs 21.04,P=0.380)。CD73高表达组显示更少的CD8^(+)(84.83 vs 121.53,P=0.029)和CD8^(+)PD-1^(+)(15.00 vs 27.27,P=0.041)T细胞数量,FOXP3^(+)数量两组无差异(45.50 vs 50.45,P=0.623)。Kaplan-Meier生存分析显示,CD73高表达以及CD8^(+)PD-1^(+)高表达患者的无进展生存期更差(P值分别为0.009和0.019)。结论TACE术后肿瘤免疫微环境CD73表达升高,而FOXP3^(+)和CD8^(+)/PD-1^(+)T细胞数量降低,而CD73高表达以及CD8^(+)PD-1^(+)高表达与患者不良预后密切相关,提示靶向CD73可能会成为TACE联合治疗的新方向。
