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Tenofovir over Entecavir on Hepatocellular Carcinoma Prevention: Potential Mechanisms and Suitable Population. 替诺福韦优于恩替卡韦预防肝细胞癌:潜在机制和适宜人群。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-01 DOI: 10.1159/000526917
Yongfa Huang, Huayu Yang, Yilei Mao
Not applicable for Letter according to Author Guidelines.
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引用次数: 1
Letter Regarding "Impact of Immune-Related Adverse Events on Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Hepatocellular Carcinoma". 关于“免疫相关不良事件对晚期肝癌患者免疫检查点抑制剂疗效的影响”的信函。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-01 DOI: 10.1159/000526804
Yinhan Wang, Yongfa Huang, Huayu Yang, Yilei Mao
Immunologic checkpoint inhibitors (ICIs) have demonstrated efficacy in a variety of malignancies. Despite impressive therapeutic benefits, ICIs may induce profound immune-related adverse events (irAEs). While the occurrence of irAEs may implicate improved T cell activity, whether irAEs predicts anti-tumor immune responses remains controversial. The paper by Kennedy Yao Yi Ng et al. adds to the evidence of the impact of irAEs in advanced hepatocellular carcinoma, which demonstrated that multi-system involvement of irAEs positively correlated with treatment responses and survival. We are, however, concerned about the grouping method and potential statistical bias. Therefore, we listed a few questions and possible solutions under each circumstance, which we would like to share with authors and readers.
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引用次数: 1
Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial. Tislelizumab在既往治疗过的晚期肝细胞癌患者中的应用(RATIONALE-208):一项多中心、非随机、开放标签的2期试验
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-01 DOI: 10.1159/000527175
Zhenggang Ren, Michel Ducreux, Ghassan K Abou-Alfa, Philippe Merle, Weijia Fang, Julien Edeline, Zhiwei Li, Lihua Wu, Eric Assenat, Sheng Hu, Lorenza Rimassa, Tao Zhang, Jean-Frédéric Blanc, Hongming Pan, Paul Ross, Chia-Jui Yen, Albert Tran, Guoliang Shao, Mohamed Bouattour, Yajin Chen, Tim Meyer, Jinlin Hou, David Tougeron, Yuxian Bai, Ming-Mo Hou, Zhiqiang Meng, John Wu, Vincent Li, Sandra Chica-Duque, Ann-Lii Cheng

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC.

Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab.

Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9-18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8-20]; two or more prior lines, 13% [95% CI, 7-20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment.

Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.

Tislelizumab(抗程序性细胞死亡蛋白1抗体)在包括肝细胞癌(HCC)在内的晚期实体肿瘤患者中显示出初步的抗肿瘤活性和耐受性。本研究旨在评估tislelizumab在既往治疗过的晚期HCC患者中的疗效和安全性。方法:多地区的2期研究RATIONALE-208检查了单药tislelizumab (200 mg静脉注射,每3周)用于Child-Pugh A,巴塞罗那临床肝癌B期或C期晚期HCC患者,并接受过一种或多种先前的全身治疗。主要终点是客观缓解率(ORR),由独立审查委员会根据实体肿瘤反应评价标准1.1版放射学证实。在接受≥1剂量tislelizumab的患者中评估安全性。结果:2018年4月9日至2019年2月27日期间,249名符合条件的患者入组并接受治疗。中位随访12.7个月后,ORR为13% (n = 32/249;95%可信区间[CI], 9-18),包括5个完整反应和27个部分反应。先前的治疗线数不影响ORR(一条既往线,13% [95% CI, 8-20];两条或多条既往线,13% [95% CI, 7-20])。中位反应持续时间未达到。疾病控制率为53%,中位总生存期为13.2个月。在249例患者中,38例(15%)患者报告了≥3级治疗相关不良事件;最常见的是10例(4%)患者的肝转氨酶升高。治疗相关不良事件导致13例(5%)患者停止治疗,46例(19%)患者延迟给药。根据研究者的评估,没有死亡归因于治疗。结论:Tislelizumab在既往治疗过的晚期HCC患者中表现出持久的客观反应,无论先前的治疗线数如何,以及可接受的耐受性。
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引用次数: 8
Front & Back Matter 正面和背面
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-01 DOI: 10.1159/000529779
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引用次数: 0
Dietary Fat Composition Affects Hepatic Angiogenesis and Lymphangiogenesis in Hepatitis C Virus Core Gene Transgenic Mice. 饲料脂肪组成对丙型肝炎病毒核心基因转基因小鼠肝脏血管生成和淋巴管生成的影响
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-01 DOI: 10.1159/000525546
Pan Diao, Yaping Wang, Fangping Jia, Xiaojing Wang, Xiao Hu, Takefumi Kimura, Yoshiko Sato, Kyoji Moriya, Kazuhiko Koike, Jun Nakayama, Naoki Tanaka

Introduction: Previous research has demonstrated that an isocaloric diet rich in trans-fatty acid (TFA), saturated fatty acid (SFA), and cholesterol (Chol) promoted steatosis-derived hepatic tumorigenesis in hepatitis C virus core gene transgenic (HCVcpTg) mice in different manners. Growth factor signaling and ensuing angiogenesis/lymphangiogenesis are key factors in hepatic tumorigenesis that have become recent therapeutic targets for hepatocellular carcinoma. However, the influence of dietary fat composition on these factors remains unclear. This study investigated whether the type of dietary fat would have a specific impact on hepatic angiogenesis/lymphangiogenesis in HCVcpTg mice.

Methods: Male HCVcpTg mice were treated with a control diet, an isocaloric diet containing 1.5% cholesterol (Chol diet), or a diet replacing soybean oil with hydrogenated coconut oil (SFA diet) for a period of 15 months or with shortening (TFA diet) for 5 months. The degree of angiogenesis/lymphangiogenesis and the expression of growth factors, including fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF), were evaluated in non-tumorous liver tissues using quantitative mRNA measurement, immunoblot analysis, and immunohistochemistry.

Results: Long-term feeding of SFA and TFA diets to HCVcpTg mice increased the expressions of vascular endothelial cell indicators, such as CD31 and TEK receptor tyrosine kinase, in addition to lymphatic vessel endothelial hyaluronan receptor 1, indicating that angiogenesis/lymphangiogenesis were upregulated only by these fatty acid-enriched diets. This promoting effect correlated with elevated VEGF-C and FGF receptor 2 and 3 levels in the liver. c-Jun N-terminal kinase (JNK) and hypoxia-inducible factor (HIF) 1α, both key regulators of VEGF-C expression, were enhanced in the SFA- and TFA-rich diet groups as well. The Chol diet significantly increased the expressions of such growth factors as FGF2 and PDGF subunit B, without any detectable impact on angiogenesis/lymphangiogenesis.

Conclusion: This study revealed that diets rich in SFA and TFA, but not Chol, might stimulate hepatic angiogenesis/lymphangiogenesis mainly through the JNK-HIF1α-VEGF-C axis. Our observations indicate the importance of dietary fat species for preventing hepatic tumorigenesis.

先前的研究表明,富含反式脂肪酸(TFA)、饱和脂肪酸(SFA)和胆固醇(Chol)的等热量饮食以不同的方式促进了丙型肝炎病毒核心基因转基因(HCVcpTg)小鼠脂肪变性肝肿瘤的发生。生长因子信号和随后的血管生成/淋巴管生成是肝肿瘤发生的关键因素,已成为肝细胞癌的最新治疗靶点。然而,膳食脂肪成分对这些因素的影响尚不清楚。本研究调查了饮食脂肪类型是否会对HCVcpTg小鼠的肝脏血管生成/淋巴管生成产生特定影响。方法:雄性HCVcpTg小鼠分别饲喂对照饮食、含1.5%胆固醇的等热量饮食(Chol饮食)、以氢化椰子油替代大豆油的饮食(SFA饮食)和起酥油(TFA饮食),为期15个月或5个月。采用定量mRNA测定、免疫印迹分析和免疫组织化学方法,评估非肿瘤肝组织中血管生成/淋巴管生成的程度和生长因子的表达,包括成纤维细胞生长因子(FGF)、血管内皮生长因子(VEGF)和血小板衍生生长因子(PDGF)。结果:HCVcpTg小鼠长期饲喂SFA和TFA日粮,除淋巴管内皮透明质酸受体1外,血管内皮细胞CD31、TEK受体酪氨酸激酶等指标的表达均增加,表明血管生成/淋巴管生成仅在这些富含脂肪酸的日粮中上调。这种促进作用与肝脏中VEGF-C和FGF受体2和3水平升高有关。c-Jun n -末端激酶(JNK)和缺氧诱导因子(HIF) 1α都是VEGF-C表达的关键调节因子,在富含SFA和tfa的饮食组中也有所增强。Chol日粮显著增加了FGF2和PDGF亚基B等生长因子的表达,但对血管生成/淋巴管生成没有明显影响。结论:本研究揭示了富含SFA和TFA而非Chol的饮食可能主要通过JNK-HIF1α-VEGF-C轴刺激肝脏血管生成/淋巴管生成。我们的观察结果表明,膳食脂肪种类对预防肝肿瘤发生的重要性。
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引用次数: 3
Was Concurrent Antibiotic Use during Immunotherapy Associated with Higher Mortality for Patients with Advanced Hepatocellular Carcinoma? 晚期肝细胞癌患者免疫治疗期间同时使用抗生素是否与较高的死亡率相关?
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-01 DOI: 10.1159/000526944
Jia-Yu Hu, Si-Yu Liu, Chen Yuan, Ying Wang, Xiang-Min Tong
aCancer Center, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China; bBengbu Medical College, Bengbu, China; cThe Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui, China; dClinical Research Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China Received: January 17, 2022 Accepted: July 19, 2022 Published online: October 10, 2022
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引用次数: 1
Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Hepatocellular Carcinoma ≤5 cm: Biological Characteristics and Patient Outcomes. ≤5cm肝细胞癌的造影增强超声肝脏成像报告和数据系统:生物学特征和患者预后。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-01-24 eCollection Date: 2023-09-01 DOI: 10.1159/000527498
Wen-Jia Cai, Minghua Ying, Rong-Qin Zheng, Jintang Liao, Baoming Luo, Lina Tang, Wen Cheng, Hong Yang, An Wei, Yilin Yang, Hui Wang, Yan-Chun Luo, Cun Liu, Hui Zhong, Qi Yang, Jie Yu, Ping Liang

Introduction: The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection.

Methods: Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed.

Results: A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection.

Conclusions: Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.

引言:本研究旨在评估肝细胞癌(HCC)的生物学特征对高危患者肝脏成像报告和数据系统(LI-RADS)v2017类别超声造影(CEUS)的影响,并比较不同类别患者根治性切除后的结果。方法:在2017年6月至2020年12月期间,前瞻性地从中国多个中心收集肝结节的标准化CEUS数据。我们对前瞻性收集的病理诊断为不超过5厘米的HCC数据进行了回顾性分析。LI-RADS类别是在对CEUS特征进行彻底评估后分配的。然后,比较CEUS LI-RADS在不同分化、Ki-67和微血管侵袭(MVI)状态下的分类和主要特征。进一步分析了不同LI-RADS类别之间无复发生存率(RFS)的差异。结果:293例患者中共有293个HCC结节。本研究显示,分化(p<0.001)和Ki-67水平(p=0.01)的HCC的CEUS LI-RADS类别存在显著差异,而分化差(LR-M为32.7%,LR-5为12%,LR-4为6.2%)(p<001)和Ki六十七高水平(中位值30%)更常被归类为LR-M类别,而分化良好(LR-4为37.5%,LR-5为15.1%,LR-M为11.5%)和Ki-67水平低(中位值11%)更常被归类为LR-4类。MVI和CEUS LI-RADS类别之间没有发现显著差异(p>0.05)。在中位随访23个月的情况下,分配到不同CEUS LI-LADS类别的HCC在切除后的RFS没有显示出显著差异。结论:HCC的生物学特征,包括分化和Ki-67表达水平,可能影响CEUS的主要特征,并影响CEUS LI-RADS的分类。不同CEUS LI-RADS类别的HCC切除后RFS无显著差异。
{"title":"Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Hepatocellular Carcinoma ≤5 cm: Biological Characteristics and Patient Outcomes.","authors":"Wen-Jia Cai,&nbsp;Minghua Ying,&nbsp;Rong-Qin Zheng,&nbsp;Jintang Liao,&nbsp;Baoming Luo,&nbsp;Lina Tang,&nbsp;Wen Cheng,&nbsp;Hong Yang,&nbsp;An Wei,&nbsp;Yilin Yang,&nbsp;Hui Wang,&nbsp;Yan-Chun Luo,&nbsp;Cun Liu,&nbsp;Hui Zhong,&nbsp;Qi Yang,&nbsp;Jie Yu,&nbsp;Ping Liang","doi":"10.1159/000527498","DOIUrl":"https://doi.org/10.1159/000527498","url":null,"abstract":"<p><strong>Introduction: </strong>The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection.</p><p><strong>Methods: </strong>Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed.</p><p><strong>Results: </strong>A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (<i>p</i> < 0.001) and levels of Ki-67 (<i>p</i> = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (<i>p</i> < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (<i>p</i> > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection.</p><p><strong>Conclusions: </strong>Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/91/lic-0012-0356.PMC10561321.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41204559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Optimizing Survival Benefit by Surgical Resection by the Seven-Eleven Criteria in Barcelona Clinic Liver Cancer Stage A/B Hepatocellular Carcinoma beyond the Milan Criteria. 在巴塞罗那诊所肝癌 A/B 期肝细胞癌中,超越米兰标准的七-十一标准优化了手术切除的生存获益。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-01-19 eCollection Date: 2023-12-01 DOI: 10.1159/000529143
Chian-Tzu Huang, Yu-Long Chu, Tung-Hung Su, Shang-Chin Huang, Tai-Chung Tseng, Shih-Jer Hsu, Sih-Han Liao, Chun-Ming Hong, Chen-Hua Liu, Hung-Chih Yang, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao

Introduction: Optimal treatment of hepatocellular carcinoma (HCC) beyond the Milan criteria is in debate. We aimed to identify candidates for surgical resection (SR) in Barcelona Clinic Liver Cancer (BCLC)-A/B HCC beyond the Milan criteria with survival benefit.

Methods: Patients with BCLC-A/B HCC beyond the Milan criteria at the National Taiwan University Hospital during 2005 and 2019 were screened, and those who received transarterial chemoembolization (TACE) or SR were consecutively included. The tumor burden was classified by the seven-eleven criteria into low (≤7), intermediate (7-11), or high (>11). Multivariable Cox proportional hazard regression analysis was used for outcome prediction.

Results: Overall, 474 patients who received SR (n = 247) and TACE (n = 227) were enrolled. Patients who underwent SR were significantly younger with better liver reserve. There were 76 (31%) and 129 (57%) deaths in the SR and TACE groups after a median follow-up of 3.9 and 2.1 years, respectively. The seven-eleven criteria could distinguish median overall survival (OS) among low (n = 149), intermediate (n = 203), and high (n = 122) tumor burden groups (7.7 vs. 6.9 vs. 2.8 years, respectively, p < 0.001). Patients receiving SR had a significantly higher median OS compared with TACE in those with intermediate (8.2 vs. 2.6 years, p < 0.001) and high (5.6 vs. 1.5 years, p = 0.001) tumor burden. After adjustment for age, sex, and liver reserve, SR was predictive for better OS in intermediate (adjusted hazard ratio [aHR]: 0.45, 95% confidence interval [CI]: 0.27-0.75) and high tumor burden groups (aHR: 0.54, 95% CI: 0.32-0.92). The survival benefit of SR especially confines to patients within 3 tumors.

Conclusions: In patients with BCLC-A/B HCC beyond the Milan criteria with tumor burden beyond the up-to-7 criteria but within 3 tumors, SR has better OS than TACE and should be considered in resectable patients.

简介:对于超越米兰标准的肝细胞癌(HCC)的最佳治疗方法仍存在争议。我们的目的是为超出米兰标准的巴塞罗那肝癌(BCLC)-A/B HCC患者确定手术切除(SR)的候选者,并使其生存获益:方法:筛选2005年至2019年期间在台湾大学医院接受经动脉化疗栓塞(TACE)或SR治疗的超出米兰标准的BCLC-A/B HCC患者。肿瘤负荷按七-十一标准分为低(≤7)、中(7-11)和高(>11)。采用多变量考克斯比例危险回归分析预测结果:共有474名患者接受了SR(247人)和TACE(227人)治疗。接受SR治疗的患者明显更年轻,肝脏储备能力更强。在中位随访3.9年和2.1年后,SR组和TACE组分别有76人(31%)和129人(57%)死亡。七-十一项标准可区分低肿瘤负荷组(149 人)、中肿瘤负荷组(203 人)和高肿瘤负荷组(122 人)的中位总生存期(OS)(分别为 7.7 年 vs. 6.9 年 vs. 2.8 年,P < 0.001)。与TACE相比,中度(8.2年对2.6年,p < 0.001)和高度(5.6年对1.5年,p = 0.001)肿瘤负荷组患者接受SR治疗的中位OS明显更高。在对年龄、性别和肝储备进行调整后,SR可预测中度肿瘤负荷组(调整后危险比[aHR]:0.45,95% 置信区间[CI]:0.27-0.75)和高度肿瘤负荷组(aHR:0.54,95% CI:0.32-0.92)更好的OS。SR的生存获益尤其局限于3个肿瘤以内的患者:结论:对于超过米兰标准的 BCLC-A/B HCC 患者,肿瘤负荷超过至多 7 个标准但不超过 3 个肿瘤,SR 的 OS 优于 TACE,可切除的患者应考虑使用 SR。
{"title":"Optimizing Survival Benefit by Surgical Resection by the Seven-Eleven Criteria in Barcelona Clinic Liver Cancer Stage A/B Hepatocellular Carcinoma beyond the Milan Criteria.","authors":"Chian-Tzu Huang, Yu-Long Chu, Tung-Hung Su, Shang-Chin Huang, Tai-Chung Tseng, Shih-Jer Hsu, Sih-Han Liao, Chun-Ming Hong, Chen-Hua Liu, Hung-Chih Yang, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao","doi":"10.1159/000529143","DOIUrl":"10.1159/000529143","url":null,"abstract":"<p><strong>Introduction: </strong>Optimal treatment of hepatocellular carcinoma (HCC) beyond the Milan criteria is in debate. We aimed to identify candidates for surgical resection (SR) in Barcelona Clinic Liver Cancer (BCLC)-A/B HCC beyond the Milan criteria with survival benefit.</p><p><strong>Methods: </strong>Patients with BCLC-A/B HCC beyond the Milan criteria at the National Taiwan University Hospital during 2005 and 2019 were screened, and those who received transarterial chemoembolization (TACE) or SR were consecutively included. The tumor burden was classified by the seven-eleven criteria into low (≤7), intermediate (7-11), or high (>11). Multivariable Cox proportional hazard regression analysis was used for outcome prediction.</p><p><strong>Results: </strong>Overall, 474 patients who received SR (<i>n</i> = 247) and TACE (<i>n</i> = 227) were enrolled. Patients who underwent SR were significantly younger with better liver reserve. There were 76 (31%) and 129 (57%) deaths in the SR and TACE groups after a median follow-up of 3.9 and 2.1 years, respectively. The seven-eleven criteria could distinguish median overall survival (OS) among low (<i>n</i> = 149), intermediate (<i>n</i> = 203), and high (<i>n</i> = 122) tumor burden groups (7.7 vs. 6.9 vs. 2.8 years, respectively, <i>p</i> < 0.001). Patients receiving SR had a significantly higher median OS compared with TACE in those with intermediate (8.2 vs. 2.6 years, <i>p</i> < 0.001) and high (5.6 vs. 1.5 years, <i>p</i> = 0.001) tumor burden. After adjustment for age, sex, and liver reserve, SR was predictive for better OS in intermediate (adjusted hazard ratio [aHR]: 0.45, 95% confidence interval [CI]: 0.27-0.75) and high tumor burden groups (aHR: 0.54, 95% CI: 0.32-0.92). The survival benefit of SR especially confines to patients within 3 tumors.</p><p><strong>Conclusions: </strong>In patients with BCLC-A/B HCC beyond the Milan criteria with tumor burden beyond the up-to-7 criteria but within 3 tumors, SR has better OS than TACE and should be considered in resectable patients.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10928811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76916642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of Local Treatment in Lymph Node Metastasis from Hepatocellular Carcinoma. 肝细胞癌淋巴结转移局部治疗的疗效。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-01-18 eCollection Date: 2023-08-01 DOI: 10.1159/000529201
Byung Min Lee, Jin-Young Choi, Jinsil Seong

Introduction: We aimed to investigate the significance of lymph node metastasis from hepatocellular carcinoma and the efficacy of local treatment.

Methods: We included patients diagnosed hepatocellular carcinoma with lymph node metastasis. The pattern of lymph node metastasis was evaluated based on imaging examinations and stratified by three locations: regional (group A), beyond regional intra-abdomen (group B), and extra-abdomen (group C) lymph node metastasis.

Results: Among 14,474 patients, 852 (5.8%) were identified as having lymph node metastasis. Regarding the location of presentation, group A showed the highest incidence, followed by groups B and C. The 1-year overall survival of patients was 31.7%. The survival significantly differed according to the location of lymph node metastasis. The 1-year overall survival rates were 39.8%, 25.5%, and 22.2% in groups A, B, and C, respectively. All patients underwent systemic treatment, with others receiving additional local treatment. Local treatment yielded superior overall survival compared with no local treatment. After propensity score matching, local treatment was associated with improved survival. Additionally, patients were stratified based on disease status at the time of diagnosis of lymph node metastasis: lymph node alone and combined extra-nodal metastasis. The survival benefits of local treatment were observed in both groups.

Conclusions: Our findings demonstrated the clinical significance of lymph node metastasis from hepatocellular carcinoma, which was well discriminated according to location, favoring regional metastasis. In patients with hepatocellular carcinoma presenting lymph node metastasis, active application of local treatment for lymph node metastasis can improve oncologic outcomes.

引言:我们旨在探讨肝细胞癌淋巴结转移的意义和局部治疗的疗效。方法:我们纳入了被诊断为肝细胞癌伴淋巴结转移的患者。根据影像学检查评估淋巴结转移模式,并按三个位置进行分层:区域(A组)、区域外腹部内(B组)和腹部外(C组)淋巴结转移。结果:14474例患者中,852例(5.8%)有淋巴结转移。就表现部位而言,A组的发病率最高,其次是B组和C组。患者的1年总生存率为31.7%。生存率因淋巴结转移部位而异。A、B和C组的1年总生存率分别为39.8%、25.5%和22.2%。所有患者都接受了全身治疗,其他患者则接受了额外的局部治疗。与不进行局部治疗相比,局部治疗的总生存率更高。倾向评分匹配后,局部治疗可提高生存率。此外,根据诊断淋巴结转移时的疾病状况对患者进行分层:单独淋巴结转移和合并淋巴结外转移。两组患者均观察到局部治疗的生存益处。结论:我们的研究结果证明了肝细胞癌淋巴结转移的临床意义,根据位置可以很好地区分,有利于区域转移。在有淋巴结转移的肝细胞癌患者中,积极应用淋巴结转移局部治疗可以改善肿瘤学结果。
{"title":"Efficacy of Local Treatment in Lymph Node Metastasis from Hepatocellular Carcinoma.","authors":"Byung Min Lee,&nbsp;Jin-Young Choi,&nbsp;Jinsil Seong","doi":"10.1159/000529201","DOIUrl":"https://doi.org/10.1159/000529201","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to investigate the significance of lymph node metastasis from hepatocellular carcinoma and the efficacy of local treatment.</p><p><strong>Methods: </strong>We included patients diagnosed hepatocellular carcinoma with lymph node metastasis. The pattern of lymph node metastasis was evaluated based on imaging examinations and stratified by three locations: regional (group A), beyond regional intra-abdomen (group B), and extra-abdomen (group C) lymph node metastasis.</p><p><strong>Results: </strong>Among 14,474 patients, 852 (5.8%) were identified as having lymph node metastasis. Regarding the location of presentation, group A showed the highest incidence, followed by groups B and C. The 1-year overall survival of patients was 31.7%. The survival significantly differed according to the location of lymph node metastasis. The 1-year overall survival rates were 39.8%, 25.5%, and 22.2% in groups A, B, and C, respectively. All patients underwent systemic treatment, with others receiving additional local treatment. Local treatment yielded superior overall survival compared with no local treatment. After propensity score matching, local treatment was associated with improved survival. Additionally, patients were stratified based on disease status at the time of diagnosis of lymph node metastasis: lymph node alone and combined extra-nodal metastasis. The survival benefits of local treatment were observed in both groups.</p><p><strong>Conclusions: </strong>Our findings demonstrated the clinical significance of lymph node metastasis from hepatocellular carcinoma, which was well discriminated according to location, favoring regional metastasis. In patients with hepatocellular carcinoma presenting lymph node metastasis, active application of local treatment for lymph node metastasis can improve oncologic outcomes.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/17/lic-0012-0218.PMC10521325.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41166805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Predictive and Prognostic Potential of Liver Function Assessment in Patients with Advanced Hepatocellular Carcinoma: A Systematic Literature Review. 晚期肝癌患者肝功能评估的预测和预后潜力:系统文献综述。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-01-17 eCollection Date: 2023-09-01 DOI: 10.1159/000529173
Arndt Vogel, Robin K Kelley, Philip Johnson, Philippe Merle, Thomas Yau, Masatoshi Kudo, Tim Meyer, Lorenza Rimassa

Introduction: We conducted a systematic literature review to assess the utility of liver function assessments for predicting disease prognosis and response to systemic anticancer therapy in patients with advanced hepatocellular carcinoma (aHCC).

Methods: This was a PRISMA-standard review and was registered with PROSPERO (CRD42021244588). MEDLINE and Embase were systematically searched (March 24, 2021) to identify publications reporting the efficacy and/or safety of systemic anticancer therapy (vs. any/no comparator) in liver-function-defined subgroups in phase 2 or 3 aHCC trials. Screening was completed by a single reviewer, with uncertainties resolved by a second reviewer and/or the authors. English-language full-text articles and congress abstracts were eligible for inclusion. Included publications were described and assessed for risk of bias using the GRADE methodology.

Results: Twenty (of 2,579) screened publications were eligible; seven categorized liver function using the albumin-bilirubin system, nine using the Child-Pugh system, four using both. GRADE assessment classified ten, nine, and one publication(s) as reporting moderate-quality, low-quality, and very-low-quality evidence, respectively. Analyses of cross-trial trends of within-exposure arm analyses (active and control) reported a positive relationship between baseline liver function and overall survival and progression-free survival, supporting liver function as a prognostic marker in aHCC. There were also signals for a modest relationship between more preserved baseline liver function and extent of systemic treatment benefit, and with more preserved liver function and lower incidence of safety events.

Conclusion: This review supports liver function as a prognostic variable in aHCC and highlights the value of a priori stratification of patients by baseline liver function in aHCC trials. The predictive value of liver function warrants further study. Findings were limited by the quality of available data.

引言:我们进行了一项系统的文献综述,以评估肝功能评估在预测晚期肝细胞癌(aHCC)患者的疾病预后和系统抗癌治疗反应方面的效用。方法:这是一项PRISMA标准综述,并在PROSPERO(CRD42021244588)注册。系统搜索MEDLINE和Embase(2021年3月24日),以确定在2期或3期aHCC试验中报告肝功能定义亚组中系统性抗癌治疗(与任何/无对照)的疗效和/或安全性的出版物。筛选由一名评审员完成,不确定性由第二名评审员和/或作者解决。英文全文文章和大会摘要符合入选条件。使用GRADE方法对纳入的出版物进行了描述和偏倚风险评估。结果:2579份筛选出版物中有20份符合条件;七项使用白蛋白-胆红素系统对肝功能进行分类,九项使用Child-Pugh系统,四项同时使用。GRADE评估将10份、9份和1份出版物分别归类为报告中等质量、低质量和极低质量证据。暴露组内分析(主动和对照)的交叉试验趋势分析报告,基线肝功能与总生存率和无进展生存率之间存在正相关,支持肝功能作为aHCC的预后标志。也有信号表明,基线肝功能更为完好与全身治疗获益程度之间存在适度关系,肝功能更完好与安全事件发生率较低之间存在适度联系。结论:这篇综述支持肝功能作为aHCC的预后变量,并强调了根据基线肝功能对患者进行先验分层在aHCC试验中的价值。肝功能的预测价值值得进一步研究。调查结果受到现有数据质量的限制。
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引用次数: 0
期刊
Liver Cancer
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