Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Camrelizumab,apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma

BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still controversial.AIM To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for Ad-HCC.METHODS From January 2018 to March 2022,217 Ad-HCC patients were retrospectively enrolled.Among them,122 were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance bias.Overall survival(OS)was compared using the Kaplan-Meier curve with the log-rank test.The overall objective response rate(ORR)and major complications were also assessed.RESULTS After PSM,82 patients were included both the T-A group and the T-M group.The ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P<0.001).The cumulative 1-,2-,and 3-year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1%,63.1%,and 55.0%in the T-A group(hazard ratio=0.22;95%confidence interval:0.10-0.49;P<0.001).The incidence of major complications was 4.9%(6/122)in the T-A group and 5.3%(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

氯胺酮复合乌司他丁对大鼠内毒素性急性肺损伤的影响

目的 探讨氯胺酮复合乌司他丁对大鼠内毒素性急性肺损伤（acute lung injury, ALI）的影响。方法 成年雄性SD大鼠100只，体重280 g ~ 320 g，采用计算机简单随机分组法随机分为5组（每组20只）：对照组（C组）、内毒素组（L组）、氯胺酮组（K组）、乌斯他丁组（U组）、氯胺酮复合乌斯他丁组（K＋U组）。除C组外，其余大鼠腹腔注射0.03 %脂多糖（lipopolysaccharide, LPS）1 mg/kg，注射后16 h时，由尾静脉再次注射0.l % LPS 1.5 mg/kg，建立大鼠ALI 模型。U组、K＋U组分别在第2次注射LPS后经尾静脉注射乌司他丁 50 000 U/kg，注射乌司他丁后即刻，K 组、K＋U 组经尾静脉以微量泵持续输注氯胺酮 10 ㎎？㎏-1？h-1，其余组注射等容量生理盐水。于第2次注射 LPS 后1、2、3、4 h （T1~4）时，各组取5只大鼠，抽取腹主动脉血样0.5 ml，测定氧分压（PaO2），抽取下腔静脉血样2 ml，测定血清肿瘤坏死因子（tumor necrosis factor，TNF）-α和白介素（interleukin，IL）-6浓度；放血处死大鼠，取右肺上叶组织，光镜下观察肺组织病理学结果，进行肺组织病理半定量评分及测定核因子（nuclear factor-κB, NF-κB）抑制蛋白α （inhibitor of nuclear factor-κBα, IκBα）表达；取右肺中叶组织100 mg测定肺组织NF-κB活性；取右肺下叶组织，计算肺湿干重比（W/D）。结果 与C组比较，L组、K组、U组和K＋U组PaO2降低，血清TNF-α、IL-6浓度和肺组织NF-κB活性升高，IκBα表达降低， W/D升高（P〈0.01）；与L组比较，K组、U组和K＋U组PaO2升高，血清TNF-α、IL-6浓度和肺组织NF-κB活性降低，IκBα表达升高，W/D降低，肺组织病理评分降低 （P〈0.05或0.01）；与K组和U组比较，K＋U组各时点PaO2升高，血清TNF-α、IL-6浓度和肺组织NF-κB活性（2.49±0.23）降低，IκBα表达（35.1±3.4）升高，W/D（4.91±0.16）降低，肺组织病理评分（7.8±0.8）降低（P〈0.05或0.01） 。结论 氯胺酮复合乌司他丁可减轻大鼠ALI，较两者单独应用效果显著。