Background: Microvascular invasion (MVI) is a significant pathological feature in hepatocellular carcinoma (HCC), adjuvant hepatic arterial infusion chemotherapy (a-HAIC) and adjuvant transcatheter arterial chemoembolization (a-TACE), are commonly used for HCC patients with MVI. This study aims to evaluate the efficacies of two adjuvant therapies after surgical treatment for HCC, compare them, and identify the significant factors. Methods: Clinical data from two randomized controlled trials involving HCC patients with MVI after surgical treatment were retrospectively reviewed. Propensity score matching (PSM) analysis was performed to balance baseline differences between patients who received a-HAIC or a-TACE, and control groups who underwent hepatectomy alone. Disease-free survival (DFS) and overall survival (OS) rates were compared. Results: In total of 549 patients were collected from two randomized controlled trials. Using the PSM and Kaplan-Meier method, the median DFS of the a-HAIC, a-TACE, and control groups was 63.2, 21.7, and 11.2 months (P< 0.05). The a-HAIC group show significantly better 1-, 3-, and 5-year OS rates compared to the a-TACE and control groups (96.3%, 80.0%, 72.8% vs 84.4%, 57.0%, 29.8% vs 84.5%, 62.8%, 53.4%, P< 0.05). But the OS rates of a-TACE and control groups showed no significant difference (P=0.279). Multivariate analysis identified a-HAIC (HR=0.449, P=0.000) and a-TACE (HR=0.633, P=0.007) as independent protective factors. For OS, a-HAIC (HR=0.388, P=0.003) was identified as an independent protective factor, too. Conclusion: Compared to a-TACE and the control group, a-HAIC demonstrated greater benefits in preventing tumor recurrence and improving survival in HCC patients with MVI.
{"title":"Hepatic Arterial Infusion Chemotherapy vs Transcatheter Arterial Chemoembolization as Adjuvant Therapy Following Surgery for MVI-Positive Hepatocellular Carcinoma: A Multicenter Propensity Score Matching Analysis","authors":"Yuhua Wen, Lianghe Lu, Jie Mei, Yihong Ling, Renguo Guan, Wenping Lin, Wei Wei, Rongping Guo","doi":"10.2147/jhc.s453250","DOIUrl":"https://doi.org/10.2147/jhc.s453250","url":null,"abstract":"<strong>Background:</strong> Microvascular invasion (MVI) is a significant pathological feature in hepatocellular carcinoma (HCC), adjuvant hepatic arterial infusion chemotherapy (a-HAIC) and adjuvant transcatheter arterial chemoembolization (a-TACE), are commonly used for HCC patients with MVI. This study aims to evaluate the efficacies of two adjuvant therapies after surgical treatment for HCC, compare them, and identify the significant factors.<br/><strong>Methods:</strong> Clinical data from two randomized controlled trials involving HCC patients with MVI after surgical treatment were retrospectively reviewed. Propensity score matching (PSM) analysis was performed to balance baseline differences between patients who received a-HAIC or a-TACE, and control groups who underwent hepatectomy alone. Disease-free survival (DFS) and overall survival (OS) rates were compared.<br/><strong>Results:</strong> In total of 549 patients were collected from two randomized controlled trials. Using the PSM and Kaplan-Meier method, the median DFS of the a-HAIC, a-TACE, and control groups was 63.2, 21.7, and 11.2 months (<em>P<</em> 0.05). The a-HAIC group show significantly better 1-, 3-, and 5-year OS rates compared to the a-TACE and control groups (96.3%, 80.0%, 72.8% vs 84.4%, 57.0%, 29.8% vs 84.5%, 62.8%, 53.4%, P< 0.05). But the OS rates of a-TACE and control groups showed no significant difference (<em>P</em>=0.279). Multivariate analysis identified a-HAIC (HR=0.449, <em>P</em>=0.000) and a-TACE (HR=0.633, <em>P</em>=0.007) as independent protective factors. For OS, a-HAIC (HR=0.388, <em>P</em>=0.003) was identified as an independent protective factor, too.<br/><strong>Conclusion:</strong> Compared to a-TACE and the control group, a-HAIC demonstrated greater benefits in preventing tumor recurrence and improving survival in HCC patients with MVI.<br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140572800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guanming Shao, Yonghui Ma, Chao Qu, Ruiqian Gao, Chengzhan Zhu, Linlin Qu, Kui Liu, Na Li, Peng Sun, Jingyu Cao
Background: Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA). Results: Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems. Conclusion: The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.
{"title":"Machine Learning Model Based on the Neutrophil-to-Eosinophil Ratio Predicts the Recurrence of Hepatocellular Carcinoma After Surgery","authors":"Guanming Shao, Yonghui Ma, Chao Qu, Ruiqian Gao, Chengzhan Zhu, Linlin Qu, Kui Liu, Na Li, Peng Sun, Jingyu Cao","doi":"10.2147/jhc.s455612","DOIUrl":"https://doi.org/10.2147/jhc.s455612","url":null,"abstract":"<strong>Background:</strong> Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA).<br/><strong>Results:</strong> Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems.<br/><strong>Conclusion:</strong> The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.<br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140572586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To explore the distribution of probable causes and clinical characteristics of non-B and non-C (NBNC) primary liver cancer (PLC) patients in the HBV-endemic region. Methods: A total of 86 individuals with biopsy-proven NBNC-PLC were enrolled. NBNC-PLC patients were defined as negative for both anti-HCV antibodies and five serum hepatitis B markers. Patients’ characteristics were collected from medical records. Results: Among them, most of the NBNC-PLC patients had intrahepatic cholangiocarcinoma (ICC) (81.4%), and 12.8% had hepatocellular carcinoma (HCC). The NBNC ICC group had more platelet count, GGT, and CA199 levels; approximately two-thirds were female, and it was more often present in patients with biliary inflammatory diseases, especially intrahepatic biliary lithiasis. The NBNC HCC group was older and had a higher proportion of dyslipidemia, obesity, cirrhosis, and AFP levels. Conclusion: Our data revealed that most of the NBNC PLC patients were ICC. Female patients with biliary inflammatory diseases and higher CA199 levels had an increased risk of ICC, and patients with metabolic risk factors and elevated AFP levels were more likely to develop HCC. Additional research should be performed to verify this finding.
{"title":"Clinical Characteristics of Non-B and Non-C Biopsy-Proven Primary Liver Cancers in an HBV- Endemic Area: A Retrospective Study","authors":"Zhen Hu, Huaying Zhou","doi":"10.2147/jhc.s455741","DOIUrl":"https://doi.org/10.2147/jhc.s455741","url":null,"abstract":"Objective: To explore the distribution of probable causes and clinical characteristics of non-B and non-C (NBNC) primary liver cancer (PLC) patients in the HBV-endemic region. Methods: A total of 86 individuals with biopsy-proven NBNC-PLC were enrolled. NBNC-PLC patients were defined as negative for both anti-HCV antibodies and five serum hepatitis B markers. Patients’ characteristics were collected from medical records. Results: Among them, most of the NBNC-PLC patients had intrahepatic cholangiocarcinoma (ICC) (81.4%), and 12.8% had hepatocellular carcinoma (HCC). The NBNC ICC group had more platelet count, GGT, and CA199 levels; approximately two-thirds were female, and it was more often present in patients with biliary inflammatory diseases, especially intrahepatic biliary lithiasis. The NBNC HCC group was older and had a higher proportion of dyslipidemia, obesity, cirrhosis, and AFP levels. Conclusion: Our data revealed that most of the NBNC PLC patients were ICC. Female patients with biliary inflammatory diseases and higher CA199 levels had an increased risk of ICC, and patients with metabolic risk factors and elevated AFP levels were more likely to develop HCC. Additional research should be performed to verify this finding.","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140772982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaxin Zhao, Cheng Wang, Liang Zhao, Huiying Zhou, Rui Wu, Tao Zhang, Jiawei Ding, Junjie Zhou, Huilin Zheng, Lei Zhang, Tianci Kong, Jie Zhou, Zhenhua Hu
Purpose: Nonsense-mediated RNA decay (NMD), a surveillance pathway for selective degradation of aberrant mRNAs, is associated with cancer progression. Its potential as a predictor for aggressive hepatocellular carcinoma (HCC) is unclear. Here, we present an innovative NMD risk model for predicting HCC prognosis
{"title":"A Novel Four-Gene Signature Based on Nonsense-Mediated RNA Decay for Predicting Prognosis in Hepatocellular Carcinoma: Bioinformatics Analysis and Functional Validation","authors":"Jiaxin Zhao, Cheng Wang, Liang Zhao, Huiying Zhou, Rui Wu, Tao Zhang, Jiawei Ding, Junjie Zhou, Huilin Zheng, Lei Zhang, Tianci Kong, Jie Zhou, Zhenhua Hu","doi":"10.2147/jhc.s450711","DOIUrl":"https://doi.org/10.2147/jhc.s450711","url":null,"abstract":"Purpose: Nonsense-mediated RNA decay (NMD), a surveillance pathway for selective degradation of aberrant mRNAs, is associated with cancer progression. Its potential as a predictor for aggressive hepatocellular carcinoma (HCC) is unclear. Here, we present an innovative NMD risk model for predicting HCC prognosis","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140767525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Baogen Zhang, Biqing Huang, Fan Yang, Jiandong Yang, Man Kong, Jing Wang, Yaoxian Xiang, Kangjie Wang, Ruchen Peng, Kun Yang, Chao An, Dong Yan
Objective: To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with transarterial chemoembolization (TACE) for the treatment of high-risk hepatocellular carcinoma (hHCC) patients. Methods: Between January 2014 and August 2022, a total of 1765 consecutive patients with hHCC who underwent initial intra-arterial therapies were reviewed and divided into a TACE group (n, 507) and a HAIC group (n, 426). The study used propensity score matching (PSM) to reduce selectivity bias. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan‒Meier curves with the Log rank test. The objective response rate (ORR), conversion surgery rate (CSR) adverse event (AE) comparison and subgroup analysis were performed between the two groups. Results: After PSM 1:1, 444 patients were divided into two groups. The patients with hHCC who received HAIC had higher median PFS (6.1 vs 3.3 months, P < 0.001) and OS (10.3 vs 8.2 months, P=0.303) than TACE. Higher ORR (24.8% vs 11.7%) and CSR (15.5% vs 8.9%) were found in the HAIC group than in the TACE group (both P < 0.05). The incidence of grade 3/4 AE was 23.9% and 8.1% in the TACE and HAIC groups, respectively. The subgroup analysis suggest that HAIC appeared to particularly benefit patients with tumor diameter of more than 10 centimeters (hazard ratio [HR], 0.6; 95% CI, 0.47– 0.77; p, 0.00) and PVTT Vp4 (HR, 0.56; 95% CI, 0.39– 0.8; P, 0.01) for PFS outperforming TACE. Conclusion: HAIC can provide better disease control for hHCC than cTACE, with a comparable long-term OS and safety.
目的比较肝动脉灌注化疗（HAIC）与经动脉化疗栓塞（TACE）治疗高危肝细胞癌（hHCC）患者的有效性和安全性：2014年1月至2022年8月期间，共对1765例接受了初次动脉内治疗的连续肝细胞癌患者进行了回顾性研究，并将其分为TACE组（507例）和HAIC组（426例）。研究采用倾向评分匹配（PSM）来减少选择性偏差。总生存期（OS）和无进展生存期（PFS）采用卡普兰-梅耶曲线和对数秩检验进行比较。对两组患者的客观反应率（ORR）、手术转化率（CSR）、不良事件（AE）进行比较，并进行亚组分析：PSM 1:1 后，444 名患者被分为两组。接受 HAIC 治疗的 hHCC 患者的中位 PFS（6.1 个月 vs 3.3 个月，P < 0.001）和 OS（10.3 个月 vs 8.2 个月，P=0.303）均高于 TACE。HAIC组的ORR（24.8% vs 11.7%）和CSR（15.5% vs 8.9%）均高于TACE组（P均为0.05）。TACE组和HAIC组的3/4级AE发生率分别为23.9%和8.1%。亚组分析表明，HAIC似乎对肿瘤直径超过10厘米（危险比[HR]，0.6；95% CI，0.47- 0.77；P，0.00）和PVTT Vp4（HR，0.56；95% CI，0.39- 0.8；P，0.01）的患者特别有益，PFS优于TACE：关键词：肝细胞癌；经动脉化疗栓塞；肝动脉灌注化疗；高风险
{"title":"High-Risk Hepatocellular Carcinoma: Hepatic Arterial Infusion Chemotherapy versus Transarterial Chemoembolization","authors":"Baogen Zhang, Biqing Huang, Fan Yang, Jiandong Yang, Man Kong, Jing Wang, Yaoxian Xiang, Kangjie Wang, Ruchen Peng, Kun Yang, Chao An, Dong Yan","doi":"10.2147/jhc.s455953","DOIUrl":"https://doi.org/10.2147/jhc.s455953","url":null,"abstract":"<strong>Objective:</strong> To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with transarterial chemoembolization (TACE) for the treatment of high-risk hepatocellular carcinoma (hHCC) patients.<br/><strong>Methods:</strong> Between January 2014 and August 2022, a total of 1765 consecutive patients with hHCC who underwent initial intra-arterial therapies were reviewed and divided into a TACE group (n, 507) and a HAIC group (n, 426). The study used propensity score matching (PSM) to reduce selectivity bias. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan‒Meier curves with the Log rank test. The objective response rate (ORR), conversion surgery rate (CSR) adverse event (AE) comparison and subgroup analysis were performed between the two groups.<br/><strong>Results:</strong> After PSM 1:1, 444 patients were divided into two groups. The patients with hHCC who received HAIC had higher median PFS (6.1 vs 3.3 months, <em>P</em> < 0.001) and OS (10.3 vs 8.2 months, <em>P</em>=0.303) than TACE. Higher ORR (24.8% vs 11.7%) and CSR (15.5% vs 8.9%) were found in the HAIC group than in the TACE group (both <em>P</em> < 0.05). The incidence of grade 3/4 AE was 23.9% and 8.1% in the TACE and HAIC groups, respectively. The subgroup analysis suggest that HAIC appeared to particularly benefit patients with tumor diameter of more than 10 centimeters (hazard ratio [HR], 0.6; 95% CI, 0.47– 0.77; p, 0.00) and PVTT Vp4 (HR, 0.56; 95% CI, 0.39– 0.8; <em>P</em>, 0.01) for PFS outperforming TACE.<br/><strong>Conclusion:</strong> HAIC can provide better disease control for hHCC than cTACE, with a comparable long-term OS and safety.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, transarterial chemoembolization, hepatic artery infusion chemotherapy, high risk<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140300501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weixun Chen, Zhengnan Hu, Ganxun Li, Lei Zhang, Tao Li
Abstract: Hepatobiliary cancer (HBC) includes hepatocellular carcinoma and biliary tract carcinoma (cholangiocarcinoma and gallbladder carcinoma), and its morbidity and mortality are significantly correlated with disease stage. Surgery is the cornerstone of curative therapy for early stage of HBC. However, a large proportion of patients with HBC are diagnosed with advanced stage and can only receive systemic treatment. According to the results of clinical trials, the first-line and second-line treatment programs are constantly updated with the improvement of therapeutic effectiveness. In order to improve the therapeutic effect, reduce the occurrence of drug resistance, and reduce the adverse reactions of patients, the treatment of HBC has gradually developed from single-agent therapy to combination. The traditional therapeutic philosophy proposed that patients with advanced HBC are only amenable to systematic therapies. With some encouraging clinical trial results, the treatment concept has been revolutionized, and patients with advanced HBC who receive novel systemic combination therapies with multi-modality treatment (including surgery, transplant, TACE, HAIC, RT) have significantly improved survival time. This review summarizes the treatment options and the latest clinical advances of HBC in each stage and discusses future direction, in order to inform the development of more effective treatments for HBC.
{"title":"The State of Systematic Therapies in Clinic for Hepatobiliary Cancers","authors":"Weixun Chen, Zhengnan Hu, Ganxun Li, Lei Zhang, Tao Li","doi":"10.2147/jhc.s454666","DOIUrl":"https://doi.org/10.2147/jhc.s454666","url":null,"abstract":"<strong>Abstract:</strong> Hepatobiliary cancer (HBC) includes hepatocellular carcinoma and biliary tract carcinoma (cholangiocarcinoma and gallbladder carcinoma), and its morbidity and mortality are significantly correlated with disease stage. Surgery is the cornerstone of curative therapy for early stage of HBC. However, a large proportion of patients with HBC are diagnosed with advanced stage and can only receive systemic treatment. According to the results of clinical trials, the first-line and second-line treatment programs are constantly updated with the improvement of therapeutic effectiveness. In order to improve the therapeutic effect, reduce the occurrence of drug resistance, and reduce the adverse reactions of patients, the treatment of HBC has gradually developed from single-agent therapy to combination. The traditional therapeutic philosophy proposed that patients with advanced HBC are only amenable to systematic therapies. With some encouraging clinical trial results, the treatment concept has been revolutionized, and patients with advanced HBC who receive novel systemic combination therapies with multi-modality treatment (including surgery, transplant, TACE, HAIC, RT) have significantly improved survival time. This review summarizes the treatment options and the latest clinical advances of HBC in each stage and discusses future direction, in order to inform the development of more effective treatments for HBC.<br/><br/><strong>Keywords:</strong> hepatobiliary cancer, systemic treatment, combination therapies<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140303302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaochen Ma, Xiangyang Sun, Fubo Xie, Wencheng Jian, Qingliang Wang, Yang Xie, Caixia Li, Kai Zhang
Aim: This study aims to explore the role of soluble programmed cell death protein 1 (sPD-1) in individuals with hepatocellular carcinoma (HCC) undergoing treatment with drug-eluting beads transarterial chemoembolization (D-TACE). Additionally, we aim to assess the potential utility of sPD-1 for determining the optimal timing for combining D-TACE with immune checkpoint inhibitors (ICIs). Materials and Methods: A total of 44 HCC patients eligible for D-TACE and 55 healthy volunteers were enrolled in this study. Three milliliters of peripheral venous blood from the patients were collected on the day before D-TACE and 3, 7, and 30 days after D-TACE, respectively, for the assay of sPD-1. The relationships between sPD-1 levels, clinical features, outcomes, and the fluctuation of sPD-1 during treatment were analyzed. Results: The initial sPD-1 levels in patients were found to be significantly higher than those in the control group. Although the initial sPD-1 levels displayed a decreasing trend with an increase in BCLC stage, no significant differences were observed among patients at different BCLC stages. The sPD-1 level on day 3 after D-TACE was similar to that on day 7 after D-TACE and significantly lower than the initial level. The sPD-1 level on day 30 after D-TACE was significantly higher than that on day 3 and day 7 after D-TACE and nearly returned to the initial level before D-TACE. Conclusion: The level of sPD-1 was found to be significantly elevated in patients with HCC. However, further research is deemed necessary to fully understand the role of sPD-1 as a potential biomarker in the initiation, progression, and prognosis of HCC. The decrease in sPD-1 following D-TACE suggests that immune effector cells might potentially be reduced, as well as immune function weakened, highlighting the need to avoid the prompt administration of ICIs after D-TACE.
Keywords: hepatocellular carcinoma, immunotherapy, soluble programmed cell death protein 1, drug-eluting beads transarterial chemoembolization
{"title":"The Influence of Drug-Eluting Beads Transarterial Chemoembolization on Serum Levels of Soluble Programmed Cell Death Protein-1 in Advanced Hepatocellular Carcinoma Patients","authors":"Xiaochen Ma, Xiangyang Sun, Fubo Xie, Wencheng Jian, Qingliang Wang, Yang Xie, Caixia Li, Kai Zhang","doi":"10.2147/jhc.s452409","DOIUrl":"https://doi.org/10.2147/jhc.s452409","url":null,"abstract":"<strong>Aim:</strong> This study aims to explore the role of soluble programmed cell death protein 1 (sPD-1) in individuals with hepatocellular carcinoma (HCC) undergoing treatment with drug-eluting beads transarterial chemoembolization (D-TACE). Additionally, we aim to assess the potential utility of sPD-1 for determining the optimal timing for combining D-TACE with immune checkpoint inhibitors (ICIs).<br/><strong>Materials and Methods:</strong> A total of 44 HCC patients eligible for D-TACE and 55 healthy volunteers were enrolled in this study. Three milliliters of peripheral venous blood from the patients were collected on the day before D-TACE and 3, 7, and 30 days after D-TACE, respectively, for the assay of sPD-1. The relationships between sPD-1 levels, clinical features, outcomes, and the fluctuation of sPD-1 during treatment were analyzed.<br/><strong>Results:</strong> The initial sPD-1 levels in patients were found to be significantly higher than those in the control group. Although the initial sPD-1 levels displayed a decreasing trend with an increase in BCLC stage, no significant differences were observed among patients at different BCLC stages. The sPD-1 level on day 3 after D-TACE was similar to that on day 7 after D-TACE and significantly lower than the initial level. The sPD-1 level on day 30 after D-TACE was significantly higher than that on day 3 and day 7 after D-TACE and nearly returned to the initial level before D-TACE.<br/><strong>Conclusion:</strong> The level of sPD-1 was found to be significantly elevated in patients with HCC. However, further research is deemed necessary to fully understand the role of sPD-1 as a potential biomarker in the initiation, progression, and prognosis of HCC. The decrease in sPD-1 following D-TACE suggests that immune effector cells might potentially be reduced, as well as immune function weakened, highlighting the need to avoid the prompt administration of ICIs after D-TACE.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, immunotherapy, soluble programmed cell death protein 1, drug-eluting beads transarterial chemoembolization<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140300508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoling Long, Huan Zeng, Yun Zhang, Qiulong Lu, Zhao Cao, Hong Shu
Purpose: Developing a high-value, convenient, and validated differential diagnosis model to differentiate alpha-fetoprotein (AFP) negative hepatic occupying lesions and assist clinicians in early identification and intervention. Patients and Methods: A total of 340 patients with AFP-negative hepatic occupying lesions who were admitted to the Guangxi Medical University Cancer Hospital between August 2021 and April 2023 were included in the final retrospective analysis. The data were randomly divided into training and validation sets in a 7:3 ratio after performing multiple interpolations. In the training set, laboratory variables and models were screened using least absolute shrinkage and selection operator regression analysis, comparison of five machine learning algorithms, and univariate, as well as multivariate logistic regression analysis. A diagnostic prediction nomogram model was developed. We evaluated and validated the model using the receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Results: We identified six significant predictive factors from the results of multivariate logistic analysis in the training set and incorporated them into the nomogram model for diagnosing AFP-negative hepatic malignant occupying lesions (HMOL). The diagnostic nomogram, including gender, age, des-gamma-carboxy prothrombin (DCP), serum ferritin (SF), AFP, and hepatitis B surface antigen (HBsAg), achieved an area under the curve of 0.905 discriminated patients with HMOL from those with benign occupying lesions. Additionally, calibration curves demonstrated the close alignment between the nomogram predictions and the ideal curve, along with the consistency between predictions and actual results. Moreover, the DCA curves illustrated indicated benefit for all patients. These finding were confirmed by the validation set. Conclusion: The GADSAH model specifically targets the discrimination of malignant and benign liver lesions in AFP-negative patients. It offers a noninvasive, cost-effective, and efficient approach for diagnosing such cases.
Keywords: hepatic occupying lesions, alpha-fetoprotein-negative, nomogram, diagnostic model
{"title":"Development of a Reliable GADSAH Model for Differentiating AFP-negative Hepatic Benign and Malignant Occupying Lesions","authors":"Xiaoling Long, Huan Zeng, Yun Zhang, Qiulong Lu, Zhao Cao, Hong Shu","doi":"10.2147/jhc.s452628","DOIUrl":"https://doi.org/10.2147/jhc.s452628","url":null,"abstract":"<strong>Purpose:</strong> Developing a high-value, convenient, and validated differential diagnosis model to differentiate alpha-fetoprotein (AFP) negative hepatic occupying lesions and assist clinicians in early identification and intervention.<br/><strong>Patients and Methods:</strong> A total of 340 patients with AFP-negative hepatic occupying lesions who were admitted to the Guangxi Medical University Cancer Hospital between August 2021 and April 2023 were included in the final retrospective analysis. The data were randomly divided into training and validation sets in a 7:3 ratio after performing multiple interpolations. In the training set, laboratory variables and models were screened using least absolute shrinkage and selection operator regression analysis, comparison of five machine learning algorithms, and univariate, as well as multivariate logistic regression analysis. A diagnostic prediction nomogram model was developed. We evaluated and validated the model using the receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA).<br/><strong>Results:</strong> We identified six significant predictive factors from the results of multivariate logistic analysis in the training set and incorporated them into the nomogram model for diagnosing AFP-negative hepatic malignant occupying lesions (HMOL). The diagnostic nomogram, including gender, age, des-gamma-carboxy prothrombin (DCP), serum ferritin (SF), AFP, and hepatitis B surface antigen (HBsAg), achieved an area under the curve of 0.905 discriminated patients with HMOL from those with benign occupying lesions. Additionally, calibration curves demonstrated the close alignment between the nomogram predictions and the ideal curve, along with the consistency between predictions and actual results. Moreover, the DCA curves illustrated indicated benefit for all patients. These finding were confirmed by the validation set.<br/><strong>Conclusion:</strong> The GADSAH model specifically targets the discrimination of malignant and benign liver lesions in AFP-negative patients. It offers a noninvasive, cost-effective, and efficient approach for diagnosing such cases.<br/><br/><strong>Keywords:</strong> hepatic occupying lesions, alpha-fetoprotein-negative, nomogram, diagnostic model<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140201279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Newsha Nikzad, David Thomas Fuentes, Millicent Roach, Tasadduk Chowdhury, Matthew Cagley, Mohamed Badawy, Ahmed Elkhesen, Manal Hassan, Khaled Elsayes, Laura Beretta, Eugene Jon Koay, Prasun Kumar Jalal
Background and Aims: Limited methods exist to accurately characterize the risk of malignant progression of liver lesions. Enhancement pattern mapping (EPM) measures voxel-based root mean square deviation (RMSD) of parenchyma and the contrast-to-noise (CNR) ratio enhances in malignant lesions. This study investigates the utilization of EPM to differentiate between HCC versus cirrhotic parenchyma with and without benign lesions. Methods: Patients with cirrhosis undergoing MRI surveillance were studied prospectively. Cases (n=48) were defined as patients with LI-RADS 3 and 4 lesions who developed HCC during surveillance. Controls (n=99) were patients with and without LI-RADS 3 and 4 lesions who did not develop HCC. Manual and automated EPM signals of liver parenchyma between cases and controls were quantitatively validated on an independent patient set using cross validation with manual methods avoiding parenchyma with artifacts or blood vessels. Results: With manual EPM, RMSD of 0.37 was identified as a cutoff for distinguishing lesions that progress to HCC from background parenchyma with and without lesions on pre-diagnostic scans (median time interval 6.8 months) with an area under the curve (AUC) of 0.83 (CI: 0.73– 0.94) and a sensitivity, specificity, and accuracy of 0.65, 0.97, and 0.89, respectively. At the time of diagnostic scans, a sensitivity, specificity, and accuracy of 0.79, 0.93, and 0.88 were achieved with manual EPM with an AUC of 0.89 (CI: 0.82– 0.96). EPM RMSD signals of background parenchyma that did not progress to HCC in cases and controls were similar (case EPM: 0.22 ± 0.08, control EPM: 0.22 ± 0.09, p=0.8). Automated EPM produced similar quantitative results and performance. Conclusion: With manual EPM, a cutoff of 0.37 identifies quantifiable differences between HCC cases and controls approximately six months prior to diagnosis of HCC with an accuracy of 89%.
Plain Language Summary: Current surveillance and diagnostic methods in hepatocellular carcinoma are suboptimal. Enhancement pattern mapping is an imaging technique that quantifies lesion signals and may be useful in diagnostic and surveillance methods. Enhancement pattern mapping describes quantifiable differences between malignant and benign liver tissue on contrast-enhanced MRI. It amplifies lesion signal and distinguishes malignancy in a surveillance population. The novel imaging technique was investigated at single institution and analyzed lesions compared to cirrhotic parenchyma. Future efforts will include further risk stratification across LI-RADS group categories. The results provide evidence that enhancement pattern mapping uses available imaging data to distinguish hepatocellular carcinoma from non-cancerous parenchyma with and without benign lesions on scans six months prior to diagnosis with standard MRI. The technique introduces a prospective modality t
{"title":"Enhancement Pattern Mapping for Early Detection of Hepatocellular Carcinoma in Patients with Cirrhosis","authors":"Newsha Nikzad, David Thomas Fuentes, Millicent Roach, Tasadduk Chowdhury, Matthew Cagley, Mohamed Badawy, Ahmed Elkhesen, Manal Hassan, Khaled Elsayes, Laura Beretta, Eugene Jon Koay, Prasun Kumar Jalal","doi":"10.2147/jhc.s449996","DOIUrl":"https://doi.org/10.2147/jhc.s449996","url":null,"abstract":"<strong>Background and Aims:</strong> Limited methods exist to accurately characterize the risk of malignant progression of liver lesions. Enhancement pattern mapping (EPM) measures voxel-based root mean square deviation (RMSD) of parenchyma and the contrast-to-noise (CNR) ratio enhances in malignant lesions. This study investigates the utilization of EPM to differentiate between HCC versus cirrhotic parenchyma with and without benign lesions.<br/><strong>Methods:</strong> Patients with cirrhosis undergoing MRI surveillance were studied prospectively. Cases (n=48) were defined as patients with LI-RADS 3 and 4 lesions who developed HCC during surveillance. Controls (n=99) were patients with and without LI-RADS 3 and 4 lesions who did not develop HCC. Manual and automated EPM signals of liver parenchyma between cases and controls were quantitatively validated on an independent patient set using cross validation with manual methods avoiding parenchyma with artifacts or blood vessels.<br/><strong>Results:</strong> With manual EPM, RMSD of 0.37 was identified as a cutoff for distinguishing lesions that progress to HCC from background parenchyma with and without lesions on pre-diagnostic scans (median time interval 6.8 months) with an area under the curve (AUC) of 0.83 (CI: 0.73– 0.94) and a sensitivity, specificity, and accuracy of 0.65, 0.97, and 0.89, respectively. At the time of diagnostic scans, a sensitivity, specificity, and accuracy of 0.79, 0.93, and 0.88 were achieved with manual EPM with an AUC of 0.89 (CI: 0.82– 0.96). EPM RMSD signals of background parenchyma that did not progress to HCC in cases and controls were similar (case EPM: 0.22 ± 0.08, control EPM: 0.22 ± 0.09, p=0.8). Automated EPM produced similar quantitative results and performance.<br/><strong>Conclusion:</strong> With manual EPM, a cutoff of 0.37 identifies quantifiable differences between HCC cases and controls approximately six months prior to diagnosis of HCC with an accuracy of 89%.<br/><br/><strong>Plain Language Summary:</strong> Current surveillance and diagnostic methods in hepatocellular carcinoma are suboptimal. Enhancement pattern mapping is an imaging technique that quantifies lesion signals and may be useful in diagnostic and surveillance methods. Enhancement pattern mapping describes quantifiable differences between malignant and benign liver tissue on contrast-enhanced MRI. It amplifies lesion signal and distinguishes malignancy in a surveillance population. The novel imaging technique was investigated at single institution and analyzed lesions compared to cirrhotic parenchyma. Future efforts will include further risk stratification across LI-RADS group categories. The results provide evidence that enhancement pattern mapping uses available imaging data to distinguish hepatocellular carcinoma from non-cancerous parenchyma with and without benign lesions on scans six months prior to diagnosis with standard MRI. The technique introduces a prospective modality t","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140165409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuan-Qin Du, Bin Yuan, Yi-Xian Ye, Feng-ling Zhou, Hong Liu, Jing-Jing Huang, Yan-Fei Wei
Background/Aims: Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) in HCC. Methods: Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-β-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot. Results: In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells. Conclusion: PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.
{"title":"Plumbagin Regulates Snail to Inhibit Hepatocellular Carcinoma Epithelial-Mesenchymal Transition in vivo and in vitro","authors":"Yuan-Qin Du, Bin Yuan, Yi-Xian Ye, Feng-ling Zhou, Hong Liu, Jing-Jing Huang, Yan-Fei Wei","doi":"10.2147/jhc.s452924","DOIUrl":"https://doi.org/10.2147/jhc.s452924","url":null,"abstract":"<strong>Background/Aims:</strong> Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) in HCC.<br/><strong>Methods:</strong> Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-β-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot.<br/><strong>Results:</strong> In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells.<br/><strong>Conclusion:</strong> PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.<br/><br/><strong>Keywords:</strong> plumbagin, hepatocellular carcinoma, epithelial-mesenchymal transition, pulmonary metastasis, Snail<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140170383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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