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Duan Y, Ding L, Meng X, Lin J, Fu H, Zhu Y, Qiu Y, Cao J, Hu J, Dong Y, Duan Y, Chen J. A therapeutic strategy integrating ultrasound-guided microwave ablation with nanocomposite hydrogels to enhance autophagy and suppress tumor growth in hepatocellular carcinoma. Acta Biomater 2025; 198:413-427. [PMID: 40246262 DOI: 10.1016/j.actbio.2025.04.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 03/25/2025] [Accepted: 04/14/2025] [Indexed: 04/19/2025]
Abstract
Microwave ablation (MWA) is widely recognized as an effective radical therapy for hepatocellular carcinoma (HCC). However, local ablation often results in a high risk of tumor recurrence. To address this challenge, we developed an effective anticancer drug delivery system comprising arsenic trioxide (As2O3)-loaded polyethylene glycol-dipalmitoylphosphatidylethanolamine (mPEG-DPPE) calcium phosphate nanoparticles (As2O3NPs) encapsulated within an injectable thermoresponsive hydrogel (ANPs-Gel). This study evaluated the therapeutic efficacy of MWA combined with ANPs-Gel in a rabbit hepatic VX2 tumor model. Ultrasound (US) and contrast-enhanced ultrasound (CEUS) were employed to assess tumor response and angiogenesis following treatment. The results demonstrated that MWA combined with ANPs-Gel significantly enhanced antitumor efficacy compared to other treatments, effectively inhibiting tumor growth and angiogenesis. Mechanistically, the therapeutic effects were associated with autophagy induced by MWA+ANPs-Gel, which played a critical role in promoting tumor cell death and suppressing epithelial-mesenchymal transition (EMT) both in vitro and in vivo. In vivo experiments further highlighted that the injectable thermoresponsive hydrogel system not only prolonged drug retention at the tumor site but also enhanced therapeutic efficacy by reducing EMT and preventing tumor recurrence. These findings suggest that MWA combined with ANPs-Gel provides a promising strategy for improving treatment outcomes in HCC through ultrasound-guided chemotherapy and targeted autophagy modulation. STATEMENT OF SIGNIFICANCE: This study introduces a potent therapeutic strategy that integrates ultrasound-guided microwave ablation (MWA) with a nanocomposite hydrogel to enhance autophagy and suppress tumor growth in hepatocellular carcinoma, as demonstrated in the rabbit VX2 hepatic tumor model. By combining advanced ultrasound guidance with a sophisticated nanomaterial platform, this approach significantly improves the efficacy of localized cancer therapy. Unlike conventional treatments, it not only ablates tumor cells but also regulates key cellular processes, such as autophagy, to amplify therapeutic outcomes. This work repurposes arsenic trioxide (Arsenic Trioxide) within a nanocomposite hydrogel delivery system and provides a detailed exploration of its therapeutic mechanisms when combined with MWA therapy. These findings pave the way for advanced clinical strategies in liver cancer management.
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Affiliation(s)
- Yi Duan
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
| | - Li Ding
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
| | - Xianwei Meng
- Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China
| | - Jiangtao Lin
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
| | - Hao Fu
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
| | - Yan Zhu
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
| | - Yijie Qiu
- Department of Ultrasound, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China
| | - Jiaying Cao
- Department of Ultrasound, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China
| | - Jian Hu
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
| | - Yi Dong
- Department of Ultrasound, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
| | - Yourong Duan
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China.
| | - Jianhua Chen
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China.
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Kudo M. Systemic Therapy Combined with Locoregional Therapy in Intermediate-stage Hepatocellular Carcinoma. INTERVENTIONAL RADIOLOGY (HIGASHIMATSUYAMA-SHI (JAPAN) 2025; 10:e20230035. [PMID: 40384918 PMCID: PMC12078074 DOI: 10.22575/interventionalradiology.2023-0035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 02/24/2024] [Indexed: 05/20/2025]
Abstract
Recent advances in systemic therapy for hepatocellular carcinoma are remarkable. The treatment goal for advanced hepatocellular carcinoma is to prolong survival, while for intermediate-stage hepatocellular carcinoma, it is to achieve a cancer-free and drug-free status. Patients unsuitable for transarterial chemoembolization may benefit from prior systemic therapy with lenvatinib or atezolizumab plus bevacizumab. The TACTICS-L trial, a prospective phase II trial, demonstrated favorable progression-free and overall survival by lenvatinib-transarterial chemoembolization sequential therapy. The REPLACEMENT trial, a multicenter, prospective, single-arm phase II trial, confirmed combination immunotherapy efficacy with atezolizumab plus bevacizumabin a population exceeding up-to-seven criteria. In a proof-of-concept study, atezolizumab plus bevacizumab plus curative therapy showed a 35% complete response rate and 23% drug-free status in intermediate-stage hepatocellular carcinoma patients with a tumor burden exceeding up-to-seven criteria.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
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Pantea R, Bednarsch J, Schmitz S, Meister P, Heise D, Ulmer F, Neumann UP, Lang SA. The assessment of impaired liver function and prognosis in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2024; 18:779-794. [PMID: 39688572 DOI: 10.1080/17474124.2024.2442573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/05/2024] [Accepted: 12/11/2024] [Indexed: 12/18/2024]
Abstract
INTRODUCTION The impairment of liver function strongly limits the therapeutic options for hepatocellular carcinoma (HCC), and the assessment of liver function is key to finding the appropriate therapy for patients suffering from this disease. Furthermore, preexisting liver dysfunction has a negative impact on the prognosis of patients in addition to the malignant potential of HCC. Hence, defining the optimal treatment of patients with HCC requires a comprehensive examination with liver function being a crucial part of it. AREAS COVERED This review will provide an overview of the currently existing methods for evaluating the liver function in patients with HCC. Assessment of liver function includes scoring systems but also functional and technical methods. In addition, the role of these tests in different treatment facilities such as liver resection, transplantation, interventional and systemic therapy is summarized. EXPERT OPINION A comprehensive pretherapeutic assessment of the liver function includes laboratory-based scoring systems, as well as imaging- and non-imaging-based functional tests. Combining diverse parameters can help to improve the safety and efficacy of HCC therapy particularly in patients with compromised liver function. Future research should focus on optimizing pretherapeutic assessment recommendations for each therapy.
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Affiliation(s)
- Roxana Pantea
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Jan Bednarsch
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Sophia Schmitz
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Phil Meister
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Daniel Heise
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Florian Ulmer
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Ulf Peter Neumann
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Sven Arke Lang
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
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Huang CF, Kroeniger K, Wang CW, Jang TY, Yeh ML, Liang PC, Wei YJ, Hsu PY, Huang CI, Hsieh MY, Lin YH, Huang JF, Dai CY, Chuang WL, Sharma A, Yu ML. Surveillance Imaging and GAAD/GALAD Scores for Detection of Hepatocellular Carcinoma in Patients with Chronic Hepatitis. J Clin Transl Hepatol 2024; 12:907-916. [PMID: 39544249 PMCID: PMC11557369 DOI: 10.14218/jcth.2024.00172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 09/17/2024] [Accepted: 09/25/2024] [Indexed: 11/17/2024] Open
Abstract
BACKGROUND AND AIMS Early detection of hepatocellular carcinoma (HCC) is crucial for improving survival in patients with chronic hepatitis. The GALAD algorithm combines gender (biological sex), age, α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC detection. Similarly, the GAAD algorithm incorporates gender (biological sex), age, AFP, and PIVKA-II. This study aimed to assess the clinical utility of AFP-L3 in the GALAD algorithm and its potential synergies with ultrasound. We compared the clinical performance of GALAD with GAAD; AFP; AFP-L3; and PIVKA-II, with or without ultrasound, in Taiwanese adults. METHODS A total of 439 serum samples were analyzed using a Cobas® e 601 analyzer (healthy controls, n = 200; chronic liver disease controls, n = 177; HCC cases, n = 62). Performance was assessed through receiver operating characteristic curve analyses to calculate the area under the curve. RESULTS The area under the curve for differentiating early-stage HCC from patients with chronic liver disease was optimal for PIVKA-II (84.9%), GAAD (79.8%), and GALAD (79.4%), with slightly improved performance for detecting all-stage HCC. Clinical performance was unaffected by disease stage or etiology. Sensitivity for early-stage HCC was highest for GAAD (57.6%) and GALAD (57.6%). Sensitivity for each strategy was further enhanced when combined with ultrasound, regardless of disease stage or etiology (P < 0.01). CONCLUSIONS These findings indicate that the role of AFP-L3 in the GALAD algorithm is minimal, supporting the use of GAAD for HCC detection. A combination of GAAD, GALAD, or PIVKA-II with ultrasound may improve diagnostic efficiency compared with recommended strategies.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- PhD Program in Translational Medicine, College of Medicine, Kaohsiung Medical University, and Academia Sinica, Kaohsiung
- Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Konstantin Kroeniger
- Clinical Algorithms & Biomarker Statistics, Roche Diagnostics GmbH, Penzberg, Germany
| | - Chih-Wen Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung
| | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Yu-Ju Wei
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung
| | - Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Ashish Sharma
- Clinical Development & Medical Affairs, Roche Diagnostics International AG, Rotkreuz, Switzerland
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Faculty of Internal Medicine, School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung
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Tang X, Chen J, Peng W, Yang Z, Hu L, Ye Z, Fu Y, Hu D, Zhou Z, Chen M, Zhang Y, Wang JC. The Efficacy and Safety of Bevacizumab Plus Anti-PD-1/PD-L1 Inhibitors in Combination with Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma. Immunotargets Ther 2024; 13:559-569. [PMID: 39478940 PMCID: PMC11524013 DOI: 10.2147/itt.s478685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 10/18/2024] [Indexed: 11/02/2024] Open
Abstract
Objection To report the efficacy and safety of triple combination therapy with bevacizumab plus anti-PD-1 (BP1) or anti-PD-L1 inhibitors (BPL) combined with hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment for initially unresectable hepatocellular carcinoma (uHCC). Methods In this retrospective study, patients with initially uHCC received either BP1-HAIC or BPL-HAIC as first-line treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Results Between January 2020 and December 2022, a total of 136 patients with initially uHCC received triple combination therapy, with 76 in the BP1-HAIC group and 60 in the BPL-HAIC group. The median PFS for the entire cohort was 11.1 months (95% CI, 8.0-13.7 months), and the median OS was 22.4 months (95% CI, 21.3- not reached). Comparative analysis revealed no significant differences in PFS (HR, 0.91, P = 0.69) or OS (HR, 0.71, P = 0.31) between the BP1-HAIC and BPL-HAIC groups. The ORR was 46.3% per RECIST v1.1 and 66.9% per mRECIST, with a DCR of 83.1% under both criteria. Common adverse events (AEs) included hypoalbuminemia and elevated aspartate/alanine aminotransferase, with 5.1% (7/136) experienced upper gastrointestinal bleeding. Multivariate Cox analysis identified tumor number and BCLC stage as independent prognostic factors for OS, and tumor number for PFS. Conclusion Triple combination therapy demonstrated significant therapeutic efficacy and tumor response in initially uHCC. No notable differences in outcomes were observed between the BP1-HAIC and BPL-HAIC groups. AEs were manageable in clinical practice.
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Affiliation(s)
- Xiang Tang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Jinbin Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Wei Peng
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Zhoutian Yang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Li Hu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Zhiwei Ye
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Yizhen Fu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Dandan Hu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Zhongguo Zhou
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Minshan Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Yaojun Zhang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Jun-Cheng Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
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Teng W, Wang HW, Lin SM, On Behalf of Diagnosis Group and Systemic Therapy Group of TLCA. Management Consensus Guidelines for Hepatocellular Carcinoma: 2023 Update on Surveillance, Diagnosis, Systemic Treatment, and Posttreatment Monitoring by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan. Liver Cancer 2024; 13:468-486. [PMID: 39435274 PMCID: PMC11493393 DOI: 10.1159/000537686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 02/02/2024] [Indexed: 10/08/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan established HCC management consensus guidelines in 2016 and updated them in 2023. Current recommendations focus on addressing critical issues in HCC management, including surveillance, diagnosis, systemic treatment, and posttreatment monitoring. For surveillance and diagnosis, we updated the guidelines to include the role of protein induced by vitamin K absence or antagonist II (PIVKA-II) and gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting HCCs. For systemic treatment, the updated guidelines summarize the multiple choices available for targeted therapy, immune checkpoint inhibitors, and a combination of both, especially for those carcinomas refractory to or unsuitable for transarterial chemoembolization. We have added a new section, posttreatment monitoring, that describes the important roles of PIVKA-II and EOB-MRI after HCC therapy, including surgery, locoregional therapy, and systemic treatment. Through this update of the management consensus guidelines, patients with HCC may benefit from optimal diagnosis, therapeutic modalities, and posttreatment monitoring.
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Affiliation(s)
- Wei Teng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hung-Wei Wang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Shi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - On Behalf of Diagnosis Group and Systemic Therapy Group of TLCA
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
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Liu Q, Zhang Y, Zhang J, Chen L, Yang Y, Liu Y. Efficacy and safety of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and immune checkpoint inhibitors in the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis in the main trunk. Front Oncol 2024; 14:1374149. [PMID: 39077472 PMCID: PMC11284057 DOI: 10.3389/fonc.2024.1374149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Accepted: 07/01/2024] [Indexed: 07/31/2024] Open
Abstract
Purpose To evaluate the efficacy and safety of mFOLFOX-based hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods This retrospective study included patients who received mFOLFOX-based HAIC combined with TKIs and ICIs from January 2021 to January 2023. The primary outcome was the objective response rate of PVTT response, and the secondary outcomes were 6-month, 1-year survival rate, overall survival (OS), and corresponding adverse events and complications were also evaluated. PVTT responses were assessed using ITK-SNAP software. Results A total of 37 patients were included in the analysis, 18.92% achieved a complete response and 56.76% achieved a partial response in PVTT response. The objective response rate (ORR) of PVTT was 75.68%. The 6-month survival rate was 89%, the 1-year survival rate was 66%, and the median OS was 15.8 months. In univariate analysis, Child-Pugh score (P=0.010) was important factor for predicting OS; in multivariate analysis, Child-Pugh score (P=0.015, HR= 3.089, 95%CI: 1.250-7.633) was the important factor for predicting OS. In terms of adverse reactions, the most common adverse reactions associated with HAIC are pain and thrombocytopenia associated with oxaliplatin. Conclusion FOLFOX-based HAIC combined with TKIs and ICIs induced an objective response rate of 75.68% in PVTT. Clinical signicance FOLFOX-based HAIC combined with TKIs and ICIs provides more treatment options for PVTT.
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Affiliation(s)
| | | | | | | | | | - Yan Liu
- Department of Interventional Radiology, Harbin Medical University Cancer Hospital, Harbin, China
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Chen HH, Lai YH, Wu CC, Hsieh WP. Cardiac-to-Bronchial Fistula in Hepatocellular Carcinoma: A Case Report. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:982. [PMID: 38929599 PMCID: PMC11205941 DOI: 10.3390/medicina60060982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 06/07/2024] [Accepted: 06/13/2024] [Indexed: 06/28/2024]
Abstract
Hepatocellular carcinoma (HCC) stands as a significant contributor to cancer-related mortality globally. While the acute and often fatal manifestations of locally advanced HCC primarily present within the abdomen, it is crucial to recognize that the respiratory and circulatory systems can also fall victim due to the liver's unique anatomical position within the body. Here, we present the case of a 63-year-old male recently diagnosed with locally advanced HCC with vascular invasion. Shortly after receiving target therapy and focal radiotherapy, the patient developed repeated secondary infections and a persistent diaphragmatic defect. As the necrotic tissue invaded the pleural space, subsequent tumor-to-bronchial and tumor-to-cardiac fistulas emerged, resulting in an abnormal connection between the respiratory and cardiovascular systems, leading to massive air emboli in circulation. This report highlights the risk of supradiaphragmatic complications in HCC patients with post-treatment secondary infections, particularly in patients predisposed to developing diaphragmatic defects.
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Affiliation(s)
| | | | | | - Wen-Pei Hsieh
- Department of Radiology, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Rd., Shilin Dist., Taipei 111, Taiwan; (H.-H.C.)
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Seth I, Siu A, Hewitt L, Budak U, Farah B, Jaber M. Clinical Practice Guidelines For the Management of Hepatocellular Carcinoma: A Systematic Review. J Gastrointest Cancer 2024; 55:318-331. [PMID: 37480425 PMCID: PMC11096239 DOI: 10.1007/s12029-023-00961-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/16/2023] [Indexed: 07/24/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, including Australia. The absence of a consensus clinical practice guideline (CPG) specific to HCC management poses challenges in reducing morbidity, mortality, and improving patient recovery. This systematic review aims to evaluate the existing evidence and assess the potential of published guidelines, including those with an international scope, to provide guidance for healthcare professionals in Australia. METHODS Electronic search of MEDLINE, Embase, Cochrane Library, Google Scholar, and PubMed was conducted. Peer-reviewed English language articles from 2005 to June 2022 were included if they described management of HCC as part of an evidence-based overall management plan or CPG. The quality of the included CPGs was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. RESULTS Twenty-one articles from 16 regions throughout the world were included in this review. All included guidelines (n = 21, 100%) recommended evaluating cirrhosis, hepatitis B, and hepatitis C as potential risk factors of HCC. Obesity and non-alcoholic fatty liver disease were recommended by 19 CPGs (91%) as risk factor for HCC. Fourteen guidelines (67%) endorsed using the BCLC staging system. Eighteen guidelines (86%) recommended a multidisciplinary approach for the management of HCC. Eighteen guidelines (86%) advised that surveillance using ultrasound should be implemented in all cirrhotic patients every 6 months regardless of the cause of cirrhosis. AGREE II mean overall assessment score was 90% indicating that all guidelines included were highly recommended in majority of domains. CONCLUSIONS The included CPGs provided a comprehensive approach, emphasizing the evaluation of risk factors, utilization of the BCLC staging system, and the importance of a multidisciplinary approach. Regular surveillance using ultrasound for cirrhotic patients was widely recommended. An understanding of contemporary international CPGs can prioritize aspects of the management of HCC to assist healthcare professionals to develop a national guideline to enable standardized, comprehensive, and evidence-based care for patients with HCC.
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Affiliation(s)
- Ishith Seth
- Illawarra Shoalhaven Local Health District, Wollongong Hospital, Wollongong, NSW, 2500, Australia.
- Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, 2522, Australia.
- School of Medicine, Graduate Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia.
- Faculty of Medicine and Health Sciences, Monash University, Victoria, 3004, Australia.
| | - Adrian Siu
- Illawarra Shoalhaven Local Health District, Wollongong Hospital, Wollongong, NSW, 2500, Australia
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, 2522, Australia
- School of Medicine, Graduate Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia
| | - Lyndel Hewitt
- Illawarra Shoalhaven Local Health District, Wollongong Hospital, Wollongong, NSW, 2500, Australia
- Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, 2522, Australia
| | - Ulvi Budak
- Illawarra Shoalhaven Local Health District, Wollongong Hospital, Wollongong, NSW, 2500, Australia
| | - Beshoy Farah
- Illawarra Shoalhaven Local Health District, Wollongong Hospital, Wollongong, NSW, 2500, Australia
| | - Mouhannad Jaber
- Illawarra Shoalhaven Local Health District, Wollongong Hospital, Wollongong, NSW, 2500, Australia
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10
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Zhao M, Guo Z, Zou YH, Li X, Yan ZP, Chen MS, Fan WJ, Li HL, Yang JJ, Chen XM, Xu LF, Zhang YW, Zhu KS, Sun JH, Li JP, Jin Y, Yu HP, Duan F, Xiong B, Yin GW, Lin HL, Ma YL, Wang HM, Gu SZ, Si TG, Wang XD, Zhao C, Yu WC, Guo JH, Zhai J, Huang YH, Wang WY, Lin HF, Gu YK, Chen JZ, Wang JP, Zhang YM, Yi JZ, Lyu N. Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations. Hepatol Int 2024; 18:4-31. [PMID: 37864725 DOI: 10.1007/s12072-023-10599-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 09/17/2023] [Indexed: 10/23/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.
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Affiliation(s)
- Ming Zhao
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, China.
- State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China.
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China.
| | - Zhi Guo
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
| | - Ying-Hua Zou
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhi-Ping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Min-Shan Chen
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Wei-Jun Fan
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Hai-Liang Li
- Department of Radiology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Ji-Jin Yang
- Department of Interventional Radiology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Xiao-Ming Chen
- Department of Interventional Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Lin-Feng Xu
- Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yue-Wei Zhang
- Hepatopancreatbiliary Center, Tsinghua University Affiliated Beijing Tsinghua Changgung Hospital, Beijing, China
| | - Kang-Shun Zhu
- Department of Minimally Invasive Interventional Radiology and Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jun-Hui Sun
- Division of Hepatobiliary and Pancreatic Surgery, Hepatobiliary and Pancreatic Interventional Treatment Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jia-Ping Li
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yong Jin
- The Interventional Therapy Department, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Hai-Peng Yu
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
| | - Feng Duan
- Department of Interventional Radiology, The General Hospital of Chinese People's Liberation Army, Beijing, China
| | - Bin Xiong
- Department of Interventional Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Guo-Wen Yin
- Department of Interventional Radiology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Hai-Lan Lin
- Department of Interventional Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Yi-Long Ma
- Department of Interventional Therapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Hua-Ming Wang
- Department of Interventional Therapy, The Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Shan-Zhi Gu
- Department of Interventional Therapy, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Tong-Guo Si
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
| | - Xiao-Dong Wang
- Departments of Interventional Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Chang Zhao
- Department of Interventional Therapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Wen-Chang Yu
- Department of Interventional Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Jian-Hai Guo
- Departments of Interventional Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jian Zhai
- Department of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Yong-Hui Huang
- Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wei-Yu Wang
- Department of Interventional Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Hai-Feng Lin
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yang-Kui Gu
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Jin-Zhang Chen
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jian-Peng Wang
- Department of Oncology, First People's Hospital of Foshan, Foshan Hospital of Sun Yat-Sen University, Foshan, China
| | - Yi-Min Zhang
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Jun-Zhe Yi
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Ning Lyu
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China
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11
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Tseng YC, Kung PT, Peng CY, Chou WY, Tsai WC. Effect of multidisciplinary team care on patient survival in chronic hepatitis B or C hepatocellular carcinoma. Front Oncol 2023; 13:1251571. [PMID: 38179172 PMCID: PMC10764426 DOI: 10.3389/fonc.2023.1251571] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 10/31/2023] [Indexed: 01/06/2024] Open
Abstract
Introduction Multidisciplinary team care coordinates with medical teams to improve the quality of cancer care. This study explored multidisciplinary team care in hepatitis B or hepatitis C virus-related hepatocellular carcinoma patients from the time of diagnosis to the first-time treatment interval and investigated treatment outcomes and prognosis. Methods This retrospective cohort study included data from a nationwide population from 2007 to 2016. Data were collected from the Taiwan Cancer Registry Database, linked to the Taiwan National Health Insurance Research Database. Propensity score matching was applied at a ratio of 1:2 to reduce the selection bias. A multiple regression model with generalized estimating equations was used to analyze whether multidisciplinary team care affected the diagnosis-to-treatment interval. The stratified Cox proportional hazards model examined whether involvement in multidisciplinary team care influenced survival status. Results A total of 10,928 and 21,856 patients with hepatocellular carcinoma received multidisciplinary and non-multidisciplinary care, respectively. Participants with multidisciplinary care had a longer diagnosis-to-treatment interval but a lower risk of cumulative cancer death (HR=0.88, 95% CI:0.84-0.92). In patients with intermediate- to advanced-stage hepatocellular carcinoma, multidisciplinary team care has obvious benefits for improving survival. Conclusion Patients with hepatocellular carcinoma who participated in multidisciplinary team care had a longer diagnosis-to-treatment interval but a lower risk of cancer death. Patients with intermediate- to advanced-stage hepatocellular carcinoma who received multidisciplinary team care significantly benefited from this outcome. Hospitals should provide HCC patients with multidisciplinary team care to improve cancer care.
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Affiliation(s)
- Yu-Chen Tseng
- Department of Public Health, China Medical University, Taichung, Taiwan
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Armed Forces General Hospital, Taichung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Pei-Tseng Kung
- Department of Healthcare Administration, Asia University, Taichung, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Wen-Yu Chou
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
| | - Wen-Chen Tsai
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
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12
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Vogel A, Grant RC, Meyer T, Sapisochin G, O'Kane GM, Saborowski A. Adjuvant and neoadjuvant therapies for hepatocellular carcinoma. Hepatology 2023:01515467-990000000-00690. [PMID: 38108634 DOI: 10.1097/hep.0000000000000726] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 11/29/2023] [Indexed: 12/19/2023]
Abstract
Immune-oncology-based regimens have shown efficacy in advanced HCC and have been implemented as standard of care as first-line therapy. Their efficacy, including high response rates, and safety justify their evaluation in earlier disease stages. Following negative results for adjuvant sorafenib in the global STORM trial in 2015, 4 global phase 3 trials, featuring different immune checkpoint inhibitor combinations, entered in parallel the race in the adjuvant setting. The IMbrave050 trial, comparing adjuvant atezolizumab in combination with bevacizumab to active surveillance following curative-intent resection or ablation, was the first to report, fast-tracking the results of the first interim analysis and demonstrating an improvement in recurrence-free survival. The trial has provoked a discussion on the horizon of expectations from adjuvant treatment and the clinical relevance of efficacy endpoints. Moreover, major pathological responses reported from early phase 2 data in the neoadjuvant setting provide a strong rationale for the evaluation of these concepts in phase 3 trials. In this review, we summarize current evidence and outline future directions for systemic therapies in early-stage HCC.
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Affiliation(s)
- Arndt Vogel
- Department of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada
- Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada
- Department of Gastroenterology, Hepatology, Infectiology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Robert C Grant
- Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Tim Meyer
- Research Department of Oncology, UCL Cancer Institute, University College London, London, UK
- Royal Free Hospital, London, UK
| | - Gonzalo Sapisochin
- Department of Abdominal Transplant & HPB Surgical Oncology, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Grainne M O'Kane
- Trinity St. James's Cancer Institute, St. James's Hospital, Dublin, Ireland
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology, Infectiology and Endocrinology, Hannover Medical School, Hannover, Germany
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13
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Kudo M. Current Therapeutic Strategies for Hepatocellular Carcinoma in Japan. Liver Cancer 2023; 12:497-509. [PMID: 38098744 PMCID: PMC10721236 DOI: 10.1159/000534304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 09/25/2023] [Indexed: 12/17/2023] Open
Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
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14
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Su TH, Huang SC, Chen CL, Hsu SJ, Liao SH, Hong CM, Tseng TC, Liu CH, Yang HC, Wu YM, Liu CJ, Chen PJ, Kao JH. Pre-operative gamma-glutamyl transferase levels predict outcomes in hepatitis B-related hepatocellular carcinoma after curative resection. J Formos Med Assoc 2023; 122:1008-1017. [PMID: 37147239 DOI: 10.1016/j.jfma.2023.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Revised: 04/01/2023] [Accepted: 04/11/2023] [Indexed: 05/07/2023] Open
Abstract
BACKGROUND Surgical resection is a curative therapy for early-stage hepatocellular carcinoma (HCC); however, HCC recurrence is not uncommon. Identifying outcome predictors helps to manage the disease. Gamma-glutamyl transferase (GGT) may predict the development of HCC, but its role to predict the outcomes after surgical resection of HCC was unclear. This study aimed to investigate pre-operative GGT levels for outcome prediction in patients with hepatitis B virus (HBV)-related HCC. METHODS We conducted a retrospective cohort study to include patients with HBV-related HCC receiving surgical resection. Clinical information, HCC characteristics and usage of antiviral therapy were collected. A time-dependent Cox proportional hazard regression analysis were used to predict HCC recurrence and survival. RESULTS A total of 699 consecutive patients with HBV-related HCC who received surgical resection with curative intent between 2004 and 2013 were included. After a median of 4.4 years, 266 (38%) patients had HCC recurrence. Pre-operative GGT positively correlated with cirrhosis, tumor burden and significantly increased in patients to develop HCC recurrence. Multivariable analysis demonstrated that pre-operative GGT ≥38 U/L increased 57% risk (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.20-2.06) of recurrent HCC after adjustment for confounding factors. Specifically, pre-operative GGT ≥38 U/L predicted early (<2 years) HCC recurrence (HR: 1.94, 95% CI: 1.30-2.89). Moreover, pre-operative GGT ≥38 U/L predicted all-cause mortality (HR: 1.73, 95% CI: 1.06-2.84) after surgery. CONCLUSION Pre-operative GGT levels ≥38 U/L independently predict high risks of HCC recurrence and all-cause mortality in HBV-related HCC patients receiving surgical resection.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Chin Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Sih-Han Liao
- National Taiwan University Cancer Center, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yao-Ming Wu
- Department of Surgery, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
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15
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Su TH, Chang SH, Chen CL, Liao SH, Tseng TC, Hsu SJ, Hong CM, Liu CH, Yang HC, Liu CJ, Chen PJ, Kao JH. Serial increase and high alpha-fetoprotein levels predict the development of hepatocellular carcinoma in 6 months. Hepatol Res 2023; 53:1021-1030. [PMID: 37291079 DOI: 10.1111/hepr.13932] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 05/23/2023] [Accepted: 06/05/2023] [Indexed: 06/10/2023]
Abstract
AIM Alpha-fetoprotein (AFP) checkup with abdominal ultrasonography for hepatocellular carcinoma (HCC) surveillance remains controversial. We evaluated a serial AFP-increase and high AFP levels in the prediction of HCC. METHODS At-risk patients with chronic liver disease underwent HCC surveillance with trimonthly AFP measurement were included and categorized into HCC and non-HCC groups. Their AFP levels at 12, 9, and 6 months (-6M) before the outcome date were evaluated. Group-based trajectory analysis and multivariable regression analysis were performed to identify AFP trajectories as risk predictors for HCC. RESULTS Overall, 2776 patients were included in the HCC (n = 326) and non-HCC (n = 2450) groups. Serial AFP levels were significantly higher in the HCC than the non-HCC groups. Trajectory analysis identified AFP-increase group (11%) increased 24-fold risks of HCC compared with the AFP-stable (89%) group. Compared with patients without the AFP-increase, a serial 3-month AFP-increase ≥10% elevated HCC risk by 12.1-fold (95% CI: 6.5-22.4) in 6 months, and the HCC risks increased 13-60 fold in patients with cirrhosis, hepatitis B, or C receiving antiviral therapy, or AFP levels <20 ng/ml. Combining serial AFP-increase ≥10% and AFP ≥20 ng/ml at -6M significantly increased 41.7-fold (95% CI: 13.8-126.2) HCC risks. In patients who underwent biannual AFP checkups, those with both 6-month AFP-increase ≥10% and AFP ≥20 ng/ml increased 22.1-fold (95% CI: 12.52-39.16) HCC risks in 6 months. Most HCCs were detected at an early stage. CONCLUSIONS Serial 3-6-month AFP-increase of ≥10% previously and AFP level of ≥20 ng/ml significantly increased HCC risks in 6 months.
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Affiliation(s)
- Tung-Hung Su
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shan-Han Chang
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sih-Han Liao
- Department of Medicine, Section of Gastroenterology, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Ming Hong
- Department of Internal Medicine, Division of Hospital Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medicine, Section of Gastroenterology, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medicine, Section of Gastroenterology, National Taiwan University Cancer Center, Taipei, Taiwan
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16
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Singal AG, Kudo M, Bruix J. Breakthroughs in Hepatocellular Carcinoma Therapies. Clin Gastroenterol Hepatol 2023; 21:2135-2149. [PMID: 36813012 PMCID: PMC10293061 DOI: 10.1016/j.cgh.2023.01.039] [Citation(s) in RCA: 72] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/22/2022] [Accepted: 01/23/2023] [Indexed: 02/24/2023]
Abstract
Several breakthroughs in hepatocellular carcinoma (HCC) therapy across tumor stages provide hope to improve its dismal prognosis. Although surgical and local ablative therapies have few significant changes in technique, an improved understanding of tumor biology has facilitated increase numbers of patients who are now eligible to undergo curative-intent procedures. Most notably, acceptable post-transplant outcomes can be achieved in well selected patients whose tumors are downstaged into Milan Criteria. Adjuvant therapy in patients at high risk of recurrence also significantly improves recurrence-free survival after resection or ablation. For patients with liver-localized disease who are not eligible for curative-intent procedures, transarterial chemoembolization (TACE) was historically the treatment modality of choice, regardless of tumor burden; however, there is now increased recognition of patients who are "TACE unsuitable" and may be better treated with systemic therapy. The greatest evolution in HCC treatment options has occurred with systemic therapy, where several new agents are now available in the first- and second-line setting, including immune checkpoint inhibitor combinations. Objective responses are observed in approximately 30% of patients and median survival is approaching 2 years. The availability of immune checkpoint inhibitors has renewed interest in combination therapies for earlier tumor stages, with several phase III trials ongoing. Considering increasing complexities of HCC care, requiring decisions between therapies delivered by different providers, multidisciplinary care is critical and is associated with improved clinical outcomes. In this review, we detail major breakthroughs in HCC therapy, how these breakthroughs can be applied in clinical practice, and remaining areas in need of further research.
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Affiliation(s)
- Amit G Singal
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas.
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka Japan.
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer Group, Liver Unit, August Pi i Sunyer Biomedical Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Hospital Clinic, University of Barcelona, Barcelona, Spain.
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17
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Chang PY, Lee RC, Liang PC, Liu YS, Chuang VP, Wu DK, Cheng YF, Huang JI, Tseng HS, Hung CF, Wu RH, Chern MC, Cheng HM, Wu CH, Cheng SM, Chiang CL, Liang HL. Multidisciplinary Taiwan consensus for the use of conventional TACE in hepatocellular carcinoma treatment. Front Oncol 2023; 13:1186674. [PMID: 37427137 PMCID: PMC10328116 DOI: 10.3389/fonc.2023.1186674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as "conventional TACE" (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.
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Affiliation(s)
- Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Yi-Sheng Liu
- Department of Medical Imagine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Vicent P. Chuang
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Ding-Kwo Wu
- Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jen-I. Huang
- Department of Radiology, Tungs’ Taichung Metroharbor Hospital, Taichung, Taiwan
| | - Hsiuo-Shan Tseng
- Department of Radiology, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Chien-Fu Hung
- Department of Radiology, Chang−Gung Memorial Hospital, Taoyuan, Taiwan
| | - Reng-Hong Wu
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Chih Chern
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Hua-Ming Cheng
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chih-Horng Wu
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - She-Meng Cheng
- Department of Radiology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chia-Ling Chiang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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18
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Kudo M. Surveillance, Diagnosis, and Treatment Outcome of Hepatocellular Carcinoma in Japan: 2023 Update. Liver Cancer 2023; 12:95-102. [PMID: 37325491 PMCID: PMC10267513 DOI: 10.1159/000530079] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 03/06/2023] [Indexed: 06/17/2023] Open
Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
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19
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Kao WY, Tan ECH, Lee HL, Huang YH, Huo TI, Chang CC, Chiou JF, Hou MC, Wu JC, Su CW. Entecavir versus tenofovir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative hepatectomy. Aliment Pharmacol Ther 2023; 57:1299-1312. [PMID: 36914943 DOI: 10.1111/apt.17438] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/27/2023] [Accepted: 02/15/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND There is still controversy about whether tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have different effects on the outcomes of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). AIMS The aim of this study was to compare the prognoses between ETV and TDF treatment among patients with HBV-related HCC after hepatectomy. METHODS An analysis was done on data from the Taiwan Cancer Registry, which was linked to Taiwan National Health Insurance Research Database, for the years 2011-2016. We identified 7107 patients with HBV-related HCC after curative hepatectomy, and 25.3% of them used ETV or TDF after surgery. After propensity score overlap weighting, 1797 patients treated with ETV (n = 1365) or TDF (n = 432) were included for analyses. Cox proportional hazards models were used to compare the efficacy of ETV and TDF for recurrence and overall survival (OS). RESULTS After hepatectomy, the recurrence rate per 100 person-years was 14.87 for the ETV group and 9.25 for the TDF group. The risk of recurrence was similar in the TDF group and the ETV group (HR [95% CI]: 0.91 [0.69-1.19; p = 0.479]), as was the risk of all-cause mortality (HR [95% CI]: 0.67 [0.42-1.07]; p = 0.091). When considering early recurrence (<2 years) and late recurrence (≧2 years), the TDF and ETV groups showed no significant differences. Subgroup analyses and sensitivity analyses demonstrated consistent results. CONCLUSION Both TDF and ETV showed similar health benefits in terms of recurrence and OS in patients with HBV-related HCC patients after hepatectomy.
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Affiliation(s)
- Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| | - Elise Chia-Hui Tan
- Department of Health Service Administration, College of Public Health, China Medical University, Taichung, Taiwan
| | - Hsin-Lun Lee
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jeng-Fong Chiou
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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20
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Liao YL, Wang TJ, Su CW, Liang SY, Liu CY, Fan JY. Efficacy of a Decision Support Intervention on Decisional Conflict Related to Hepatocellular Cancer Treatment: A Randomized Controlled Trial. Clin Nurs Res 2023; 32:233-243. [PMID: 36082423 DOI: 10.1177/10547738221121447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The purpose of this study was to investigate the efficacy of decision support intervention on treatment knowledge, decision self-efficacy, decisional conflict, and decision satisfaction in patients with hepatocellular cancer. The study was a randomized controlled trial. In all, 69 patients with hepatocellular carcinoma (HCC) were recruited and randomly assigned to a decision support group or a control group. Data were collected at baseline, post-test, and follow-up using self-report questionnaires. After controlling for baseline scores, the between-group difference (95% confidence interval [CI]) for treatment-related knowledge in post-test scores was 11.9 (6.1, 17.8). After controlling for baseline scores, the between-group difference (95% CI) for decisional conflict was -7.0 (-12.0, -2.0). There was no statistically significant between-group difference in decision self-efficacy and decision satisfaction. Findings supported the efficacy of decision support intervention to improve treatment knowledge and reduce decisional conflict but had no significant effect on decision self-efficacy and decision satisfaction in patients with HCC.
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Affiliation(s)
- Yueh-Ling Liao
- Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan
| | - Tsae-Jyy Wang
- National Taipei University of Nursing and Health Sciences, Taipei
| | - Chien-Wei Su
- Taipei Veterans General Hospital, Taipei
- National Yang Ming Chiao Tung University, Taipei
- National Tsing Hua University, Hsinchu
| | - Shu-Yuan Liang
- National Taipei University of Nursing and Health Sciences, Taipei
| | - Chieh-Yu Liu
- National Taipei University of Nursing and Health Sciences, Taipei
| | - Jun-Yu Fan
- Chang Gung University of Science and Technology Linkou Campus, Taoyuan
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21
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Chen SL, Ho CY, Lin WC, Lee CW, Chen YC, Chen JL, Chen HY. The Characteristics and Mortality of Chinese Herbal Medicine Users among Newly Diagnosed Inoperable Huge Hepatocellular Carcinoma (≥10 cm) Patients: A Retrospective Cohort Study with Exploration of Core Herbs. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph191912480. [PMID: 36231778 PMCID: PMC9564474 DOI: 10.3390/ijerph191912480] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 09/19/2022] [Accepted: 09/27/2022] [Indexed: 05/03/2023]
Abstract
For patients with inoperable huge hepatocellular carcinoma (H-HCC, tumor size ≥10 cm), treatment options are limited. This study aimed to evaluate the characteristics and outcomes of patients with H-HCC who use Chinese herbal medicine (CHM). Multi-institutional cohort data were obtained from the Chang Gung Research Database (CGRD) between 1 January 2002 and 31 December 2018. All patients were followed up for 3 years or until the occurrence of death. Characteristics of CHM users and risk of all-cause mortality were assessed, and core CHMs with potential pharmacologic pathways were explored. Among 1618 patients, clinical features of CHM users (88) and nonusers (1530) were similar except for lower serum α-fetoprotein (AFP) and higher serum albumin levels in CHM users. CHM users had significantly higher 3 year overall survival rates (15.0% vs. 9.7%) and 3 year liver-specific survival rates (13.4% vs. 10.7%), about 3 months longer median survival time, and lower risk of all-cause mortality. Core CHMs were discovered from the prescriptions, including Hedyotis diffusa Willd combined with Scutellaria barbata D.Don, Salvia miltiorrhiza Bunge., Curcuma longa L., Rheum palmatum L., and Astragalus mongholicus Bunge. CHM use appears safe and is possibly beneficial for inoperable H-HCC patients; however, further clinical trials are still required.
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Affiliation(s)
- Shu-Ling Chen
- Division of Chinese Internal and Pediatric Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan Branch, Taoyuan 333, Taiwan
| | - Chia-Ying Ho
- Division of Chinese Internal and Pediatric Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan Branch, Taoyuan 333, Taiwan
| | - Wei-Chun Lin
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan
| | - Chao-Wei Lee
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan
| | - Yu-Chun Chen
- Department of Family Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei 112, Taiwan
| | - Jiun-Liang Chen
- Division of Chinese Internal and Pediatric Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan Branch, Taoyuan 333, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Hsing-Yu Chen
- Division of Chinese Internal and Pediatric Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan Branch, Taoyuan 333, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Correspondence: ; Tel.: +886-975366119; Fax: +886-3-3298995
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22
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Jang TY, Dai CY. Cutoff values of protein induced by vitamin K absence or antagonist II for diagnosing hepatocellular carcinoma. Medicine (Baltimore) 2022; 101:e30936. [PMID: 36181046 PMCID: PMC9524990 DOI: 10.1097/md.0000000000030936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Protein induced by vitamin K absence or antagonist II (PIVKA-II) is a promising serum marker for hepatocellular carcinoma (HCC). There are limited data on its cutoff value in HCC for Taiwanese cirrhosis patients. This study aimed to investigate the diagnostic value of PIVKA-II levels in patients with suspected HCC. In total, 88 patients with chronic hepatitis and suspected HCC by ultrasound, elevated α-fetoprotein (AFP) or PIVKA-II levels were consecutively enrolled. Their baseline characteristics and findings on dynamic phases of computed tomography (CT) or magnetic resonance imaging (MRI) were examined. Sixty participants had cirrhosis and 34 had HCC. The median levels of PIVKA-II in non-cirrhosis and cirrhosis patients without or with HCC were 28.0, 48.0, and 847.0 mAU/mL, respectively. The optimal cutoff value of PIVKA-II in predicting HCC was 78.0 mAU/mL. Combining AFP with PIVKAII mildly increased its diagnostic performance for HCC, yielding higher specificity and positive predictive value. Significant factors predicting HCC in multivariate regression analysis were PIVKA >78.0 mAU/mL and fatty liver. Monitoring PIVKA-II level is suitable for noninvasively assessing HCC in patients with chronic hepatitis, particularly with AFP.
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Affiliation(s)
- Tyng-Yuan Jang
- PhD Program of Environmental and Occupational Medicine and Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Ping-Tung, Taiwan
| | - Chia-Yen Dai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- *Correspondence: Chia-Yen Dai, Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou Road, Kaohsiung City 807, Taiwan (e-mail: )
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23
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Wang SY, Su TH, Chen BB, Liu CJ, Liu CH, Yang HC, Tseng TC, Chen PJ, Kao JH. Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) predicts complete responses of transarterial chemoembolization for hepatocellular carcinoma. J Formos Med Assoc 2022; 121:1579-1587. [PMID: 35078686 DOI: 10.1016/j.jfma.2022.01.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 12/16/2021] [Accepted: 01/05/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND/PURPOSE Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is a diagnostic marker for hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is the standard management for intermediate stage HCC but lacks effective response predictors. We investigated the utility of PIVKA-II as a predictor of TACE response. METHODS This prospective study included consecutive patients with HCC undergoing TACE in Taiwan. Serum PIVKA-II levels were measured before and serially after TACE. Multivariable analyses were conducted to evaluate predictors of mortality, complete responses (CR) to TACE and unTACEable progression. RESULTS We included 46 patients with HCC (median age: 64 years, men:72%), and Barcelona Clinic Liver Cancer (BCLC) stages A (17%), B (65%), or C (17%). Before TACE, the median PIVKA-II level was 189 mAU/mL. After a median follow-up of 16 months, 27 (59%) patients died. PIVKA-II was positively correlated with tumor burden. Patients with infiltrative HCC or HCC exceeding the up-to-7 criteria had significantly higher baseline PIVKA-II levels than those without. Multivariable analysis indicated the infiltrative HCC independently predicted mortality. In patients BCLC A and B (n = 38), low baseline PIVKA-II (<26 mAU/mL) predicted CR to TACE, whereas high PIVKA-II predicted unTACEable tumor progression. Observations from a validation cohort corroborated the initial result that low PIVKA-II predicts CR. Moreover, serial PIVKA-II levels post TACE were significantly lower in patients with a CR to TACE compared with those without. CONCLUSION Low baseline PIVKA-II level helps to predict a CR of TACE in patients with HCC.
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Affiliation(s)
- Sung-Yin Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Bang-Bin Chen
- Department of Radiology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
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24
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Su TH, Hsu SJ, Kao JH. Paradigm shift in the treatment options of hepatocellular carcinoma. Liver Int 2022; 42:2067-2079. [PMID: 34515412 DOI: 10.1111/liv.15052] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 01/27/2023]
Abstract
Hepatocellular carcinoma (HCC) is prevalent worldwide with suboptimal therapeutic outcomes. The advancement of therapeutic options and the development of new systemic therapies expand the armamentarium to tackle HCC. Treatment options should be provided based on the hierarchy of efficacy in a multidisciplinary perspective, instead of the traditional stage-guided scheme. In advanced HCC, lenvatinib has a comparable efficacy as sorafenib for the first-line therapy of HCC; while regorafenib, cabozantinib, and ramucirumab have been approved as second-line therapy after the failure of sorafenib. Immune checkpoint inhibitor therapy prolongs response rate and survival and enables long-term cure. Atezolizumab plus bevacizumab is superior to sorafenib as the first-line therapy for advanced HCC. Several emerging regimens by the combination of various systemic therapies are currently under clinical trials. Systemic therapy may be used in the neoadjuvant, adjuvant or even as initial therapy for intermediate-stage HCC. The paradigm shift of HCC treatment will improve patient outcomes.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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25
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Wu CH, Lee YH, Liang PC, Hu RH, Shih TTF, Ho MC. Predictors of changes in preoperative tumor stage between dynamic computed tomography and gadoxetate disodium-enhanced magnetic resonance imaging for hepatocellular carcinoma. J Formos Med Assoc 2022; 121:1550-1559. [PMID: 35033411 DOI: 10.1016/j.jfma.2021.12.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/27/2021] [Accepted: 12/28/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND/PURPOSE Gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) has a higher diagnostic accuracy for hepatocellular carcinoma (HCC) than computed tomography (CT). However, indications for performing EOB-MRI after dynamic CT are not well defined. Therefore, we investigated the clinical factors associated with changes in the preoperative tumor stage between dynamic CT and EOB-MRI. METHODS A prospective cohort was conducted from January 2014 to December 2017. 156 adult patients with clinical suspicion of HCC before liver resection were enrolled and we retrospectively reviewed the images. The tumor staging was evaluated by dynamic CT and then EOB-MRI subsequently according to the TNM staging system. The changes in tumor stage between two modalities were identified, and the associated clinical factors were analyzed. RESULTS A total of 99 patients were analyzed after excluding 57 patients. 20 patients (20.2%) had changes in tumor stage between dynamic CT and EOB-MRI. The change occurred only in early stage (T1 and T2 lesions) based on dynamic CT initially. Furthermore, in univariate and multivariate analyses, albumin-bilirubin (ALBI) grade 2 and log alpha-fetoprotein (AFP) levels were associated with changes in tumor staging by EOB-MRI than those without (50% vs. 9.9%, p < 0.001 and 2.04 ± 1.35 vs. 1.40 ± 1.16, p = 0.038, respectively). Patients with changes in tumor stage also exhibited higher 1-year recurrence rate and shorter recurrence-free survival. CONCLUSION Changes in preoperative tumor stage between dynamic CT and EOB-MRI were associated with CT-defined early stage, ALBI grades, higher log AFP levels, and early recurrence.
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Affiliation(s)
- Chih-Horng Wu
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Hsin Lee
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Rey-Heng Hu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tiffany Ting-Fang Shih
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Center for Functional Image and Interventional Image, National Taiwan University, Taipei, Taiwan; Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
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26
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Lu HZ, Mai RY, Wang XB, Chen J, Bai T, Ma L, Xiang BD, Cheng SQ, Guo WX, Li LQ, Ye JZ. Developmental artificial neural network model to evaluate the preoperative safe limit of future liver remnant volume for HCC combined with clinically significant portal hypertension. Future Oncol 2022; 18:2683-2694. [PMID: 35699041 DOI: 10.2217/fon-2021-1297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Background & aims: Finding a way to comprehensively integrate the presence and grade of clinically significant portal hypertension, amount of preserved liver function and extent of hepatectomy into the guidelines for choosing appropriate candidates to hepatectomy remained challenging. This study sheds light on these issues to facilitate precise surgical decisions for clinicians. Methods: Independent risk factors associated with grade B/C post-hepatectomy liver failure were identified by stochastic forest algorithm and logistic regression in hepatitis B virus-related hepatocellular carcinoma patients. Results: The artificial neural network model was generated by integrating preoperative pre-ALB, prothrombin time, total bilirubin, AST, indocyanine green retention rate at 15 min, standard future liver remnant volume and clinically significant portal hypertension grade. In addition, stratification of patients into three risk groups emphasized significant distinctions in the risk of grade B/C post-hepatectomy liver failure. Conclusion: The authors' artificial neural network model could provide a reasonable therapeutic option for clinicians to select optimal candidates with clinically significant portal hypertension for hepatectomy and supplement the hepatocellular carcinoma surgical treatment algorithm.
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Affiliation(s)
- Hua-Ze Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Rong-Yun Mai
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xiao-Bo Wang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jie Chen
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Liang Ma
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.,Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.,National Research Cooperative Group for Diagnosis and Treatment of Hepatocellular Carcinoma with Tumor Thrombus, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.,National Research Cooperative Group for Diagnosis and Treatment of Hepatocellular Carcinoma with Tumor Thrombus, China
| | - Jia-Zhou Ye
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
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Liu DM, Leung TW, Chow PK, Ng DC, Lee RC, Kim YH, Mao Y, Cheng YF, Teng GJ, Lau WY. Clinical consensus statement: Selective internal radiation therapy with yttrium 90 resin microspheres for hepatocellular carcinoma in Asia. Int J Surg 2022; 102:106094. [PMID: 35662438 DOI: 10.1016/j.ijsu.2021.106094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is subject to different management approaches and guidelines according to Eastern and Western therapeutic algorithms. Use of selective internal radiation therapy (SIRT) with resin yttrium 90 microspheres for HCC has increased in Asia in recent years, without clearly defined indications for its optimal application. The objective of this systematic review and expert consensus statement is to provide guidance and perspectives on the use of SIRT among patients with HCC in Asia. MATERIALS AND METHODS A systematic literature review identified current publications on HCC management and SIRT recommendations. A group of 10 experts, representing stakeholder specialties and countries, convened between August 2020 and March 2021 and implemented a modified Delphi consensus approach to develop guidelines and indications for use of SIRT for HCC in Asia. Final recommendations were organized and adjudicated based on the level of evidence and strength of recommendation, per approaches outlined by the American College of Cardiology/American Heart Association and Oxford Centre for Evidence-Based Medicine. RESULTS The experts acknowledged a general lack of evidence relating to use of SIRT in Asia and identified as an unmet need the lack of phase 3 randomized trials comparing clinical outcomes and survival following SIRT versus other therapies for HCC. Through an iterative process, the expert group explored areas of clinical relevance and generated 31 guidance statements and a patient management algorithm that achieved consensus. CONCLUSION These recommendations aim to support clinicians in their decision-making and to help them identify and treat patients with HCC using SIRT in Asia. The recommendations also highlight areas in which further clinical trials are needed to define the role of SIRT in management of HCC among Asian populations.
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Affiliation(s)
- David M Liu
- Department of Radiology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Thomas Wt Leung
- Comprehensive Oncology Centre, Hong Kong Sanatorium & Hospital, Hong Kong
| | - Pierce Kh Chow
- National Cancer Centre Singapore, Singapore General Hospital, Duke-NUS Medical School, Singapore
| | - David Ce Ng
- Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Duke-NUS Medical School, Singapore
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yun Hwan Kim
- Department of Radiology, Presbyterian Medical Center, Jeonju, South Korea
| | - Yilei Mao
- Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, China
| | - Yu-Fan Cheng
- Department of Diagnostic Radiology, Liver Transplantation Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Gao-Jun Teng
- Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Wan Yee Lau
- Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong.
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Bae BK, Park HC, Yoo GS, Choi MS, Oh JH, Yu JI. The Significance of Systemic Inflammation Markers in Intrahepatic Recurrence of Early-Stage Hepatocellular Carcinoma after Curative Treatment. Cancers (Basel) 2022; 14:2081. [PMID: 35565210 PMCID: PMC9102776 DOI: 10.3390/cancers14092081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/11/2022] [Accepted: 04/18/2022] [Indexed: 12/21/2022] Open
Abstract
Systemic inflammatory markers (SIMs) are known to be associated with carcinogenesis and prognosis of hepatocellular carcinoma (HCC). We evaluated the significance of SIMs in intrahepatic recurrence (IHR) of early-stage HCC after curative treatment. This study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC between 2005 and 2017 at a single institution. Inclusion criteria were patients with Barcelona Clinic Liver Cancer stage 0 or A, who underwent curative treatment. Pre-treatment and post-treatment values of platelet, neutrophil, lymphocyte, monocyte, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) were analyzed with previously well-known risk factors of HCC to identify factors associated with IHR-free survival (IHRFS), early IHR, and late IHR. Of 4076 patients, 2142 patients (52.6%) experienced IHR, with early IHR in 1018 patients (25.0%) and late IHR in 1124 patients (27.6%). Pre-treatment platelet count and PLR and post-treatment worsening of NLR, PLR, and LMR were independently associated with IHRFS. Pre-treatment platelet count and post-treatment worsening of NLR, PLR, and LMR were significantly related to both early and late IHR. Pre-treatment values and post-treatment changes in SIMs were significant factors of IHR in early-stage HCC, independent of previously well-known risk factors of HCC.
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Affiliation(s)
- Bong Kyung Bae
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| | - Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (M.S.C.); (J.H.O.)
| | - Joo Hyun Oh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (M.S.C.); (J.H.O.)
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
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Reappraisal of the roles of alpha-fetoprotein in hepatocellular carcinoma surveillance using large-scale nationwide database and hospital-based information. J Formos Med Assoc 2022; 121:2085-2092. [PMID: 35450743 DOI: 10.1016/j.jfma.2022.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 03/22/2022] [Accepted: 04/05/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND/PURPOSE Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels. METHODS This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017. RESULTS The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC. CONCLUSION This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.
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Masuda S, Tsukiyama T, Minagawa Y, Koizumi K, Kako M, Kinbara T, Haruki U. Hepatocellular carcinoma effective stereotactic body radiotherapy using Gold Anchor and the Synchrony system: Two case reports and review of literature. World J Clin Cases 2022; 10:2591-2603. [PMID: 35434047 PMCID: PMC8968590 DOI: 10.12998/wjcc.v10.i8.2591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 11/12/2021] [Accepted: 01/29/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Radiotherapy for hepatocellular carcinoma (HCC) is considered to have limited efficacy because of treatment intensity considering that the irradiated area includes the liver, which is highly radiosensitive. In this report, we present two cases in which tumor control by surgical resection, radiofrequency ablation, transcatheter arterial chemoembolization (TACE), and lenvatinib administration was difficult, but stereotactic body radiotherapy (SBRT) using the Synchrony system by Radixact™ and Gold Anchor® (GA) was effective.
CASE SUMMARY A 60-year-old man had a single 10-cm HCC in the right lobe. Viable lesions remained after TACE, and levels of alpha-fetoprotein and protein induced by vitamin K antagonists II (PIVKA-II) decreased and quickly re-elevated. We performed SBRT with GA. Three weeks after implantation, localized radiotherapy (SBRT; 40 Gy/5 fractions) was performed using the Synchrony system by Radixact™. Four weeks later, the viable lesion had disappeared, and the PIVKA-II levels decreased. A 77-year-old man had a single 12-cm HCC in the right lobe. The patient experienced recurrence after hepatectomy. Further recurrence occurred after TACE, and we performed SBRT with GA. Because of the proximity of the HCC to the gastrointestinal tract, localized radiotherapy (SBRT; 39 Gy/13 fractions) to the HCC was performed 3 wk after implantation using the Synchrony system by Radixact™. Four weeks later, the viable lesion had disappeared on computed tomography, and the PIVKA-Ⅱ levels decreased.
CONCLUSION SBRT using the Synchrony system and GA can deliver a large dose accurately and safely, and could have a high therapeutic effect.
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Affiliation(s)
- Sakue Masuda
- Department of Gastroenterology, Shonankamakura General Hospital, Kanagawa 247-8533, Japan
| | - Toshitaka Tsukiyama
- Department of Interventional Radiology Center, Shonan Kamakura General Hospital, Kanagawa 247-8533, Japan
| | - Yumiko Minagawa
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kanagawa 247-8533, Japan
| | - Kazuya Koizumi
- Department of Gastroenterology, Shonankamakura General Hospital, Kanagawa 247-8533, Japan
| | - Makoto Kako
- Department of Gastroenterology, Shonankamakura General Hospital, Kanagawa 247-8533, Japan
| | - Takeshi Kinbara
- Department of Gastroenterology, Shonankamakura General Hospital, Kanagawa 247-8533, Japan
| | - Uojima Haruki
- Department of Gastroenterology, Shonankamakura General Hospital, Kanagawa 247-8533, Japan
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Novick D, Rajan N, Wei A, Cheng R, Szende A, Baik R, Colman S. Treatment Patterns and Health Resource Utilization in Patients With Hepatocellular Carcinoma After Failure of Sorafenib in Real-World Setting in Taiwan. Value Health Reg Issues 2022; 30:76-82. [PMID: 35278836 DOI: 10.1016/j.vhri.2022.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 10/29/2021] [Accepted: 01/11/2022] [Indexed: 11/19/2022]
Abstract
OBJECTIVES This study aimed to characterize current treatment patterns and healthcare resource utilization (HRU) observed among patients with hepatocellular carcinoma (HCC) after the failure of sorafenib in real-world setting in Taiwan. METHODS A chart review was conducted in 130 patients; the inclusion criteria were patients with HCC who were aged 20 years or older and had received systemic therapy or best supportive care after failure of first-line systemic treatment with sorafenib between 2016 and 2018. Anonymized data on patient characteristics, treatment pathways, and survival were abstracted. RESULTS The mean age of patients was 61.7 years (range 27-84); of these 130 patients, 103 (79%) were male, 81 (62%) had high alpha-fetoprotein (AFP) levels (≥400 ng/mL), and 96 (78.0%) were deceased at the time of data abstraction. After sorafenib therapy, 60 patients (46%) received systemic therapy, including nivolumab monotherapy (42%) and chemotherapy (25%). Oncologist visits at a semiannual per-patient rate of 3.7 (95% confidence interval [CI] 3.4-4.0) and hospitalizations at rate of 1.1 (95% CI 1.0-1.3) were the key contributors to HRU. Semiannual per-patient hospitalization rate was 1.3 (95% CI 1.1-1.5) in the high-AFP group. Median survival from discontinuation of sorafenib was 6.9 months (95% CI 5.9-9.0). CONCLUSIONS This real-world evidence research on treatment patterns reflected substantial HRU consistent with the severity of HCC, particularly in the high-AFP group. Findings highlighted continuing high mortality in HCC, underlying a need for new treatments that can lengthen survival. Results can inform future evaluations of new HCC treatments that estimate the health economic impact of their adoption in Taiwan.
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Affiliation(s)
| | | | - Alice Wei
- Eli Lilly and Company, Taipei, Taiwan
| | | | - Agota Szende
- Labcorp Market Access Services, Leeds, England, UK
| | - Rebecca Baik
- Labcorp Market Access Services, Gaithersburg, MD, USA
| | - Sam Colman
- Labcorp Market Access Services, Sydney, Australia
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Su TH, Peng CY, Chang SH, Tseng TC, Liu CJ, Chen CL, Liu CH, Yang HC, Chen PJ, Kao JH. Serum PIVKA-II and alpha-fetoprotein at virological remission predicts hepatocellular carcinoma in chronic hepatitis B related cirrhosis. J Formos Med Assoc 2022; 121:703-711. [PMID: 34452785 DOI: 10.1016/j.jfma.2021.08.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/18/2021] [Accepted: 08/02/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The risk of hepatocellular carcinoma (HCC) is reduced but not eliminated after nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB). We aimed to investigate the role of serum Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) and alpha-fetoprotein in predicting HCC and mortality in cirrhotic CHB patients at virological remission (VR) following NA therapy. METHODS Patients with CHB-related cirrhosis undergoing NA therapy from two medical centers in Taiwan were retrospectively included. Serum PIVKA-II were quantified by an automated chemiluminescence assay. Multivariable Cox proportional hazards regression models were used to identify predictors for HCC and death. Serial on-treatment PIVKA-II levels after VR were investigated. RESULTS Overall, 293 CHB-related cirrhosis patients were included. At VR, the mean age was 55, and the mean PIVKA-II level was 35 mAU/mL. After a mean follow-up of 78 months, 76 patients developed HCC and 19 died. After adjustment for confounding factors, alpha-fetoprotein >7 ng/mL (hazard ratio [HR]: 2.84, 95% confidence interval [CI]: 1.73-4.67) and PIVKA-II >50 mAU/mL (HR: 2.46, 95%CI: 1.35-4.49) at VR significantly predicted HCC development. In patients with alpha-fetoprotein ≤10 ng/mL or ≤20 ng/mL at VR, PIVKA-II >50 mAU/mL increased 2.45 or 3.16-fold risk of HCC, respectively. PIVKA-II levels after VR increased serially in patients who developed HCC afterwards. CONCLUSION In patients with CHB-related cirrhosis, serum alpha-fetoprotein >7 ng/mL and PIVKA-II >50 mAU/mL at the time of antiviral therapy-induced VR is associated with a greater risk of HCC. PIVKA-II is a predictive marker for HCC in patients with low normal alpha-fetoprotein level.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- School of Medicine, China Medical University, Taichung, Taiwan; Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Shan-Han Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
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Shen YC, Hsu HC, Lin TM, Chang YS, Hu LF, Chen LF, Lin SH, Kuo PI, Chen WS, Lin YC, Chen JH, Liang YC, Chang CC. H1-Antihistamines Reduce the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus, Hepatitis C Virus, or Dual Hepatitis B Virus-Hepatitis C Virus Infection. J Clin Oncol 2022; 40:1206-1219. [PMID: 35044851 PMCID: PMC8987217 DOI: 10.1200/jco.21.01802] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
H1-antihistamines (AHs) may exert protective effects against cancer. This study investigated the association of AH use with the risk of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or dual HBV-HCV virus infection.
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Affiliation(s)
- Yu-Chuan Shen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Hui-Ching Hsu
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Tzu-Min Lin
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yu-Sheng Chang
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Li-Fang Hu
- Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Lung-Fang Chen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Sheng-Hong Lin
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Pei-I Kuo
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Cardinal Tien Hospital, Yonghe Branch, Taipei, Taiwan
| | - Wei-Sheng Chen
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Chun Lin
- Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Jin-Hua Chen
- Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Yu-Chih Liang
- School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Chi-Ching Chang
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
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34
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Yen YH, Li WF, Kee KM, Wang CC, Cheng YF, Wang JH, Lu SN, Hung CH. The characteristics of patients with macrovascular invasion in hepatocellular carcinoma: when East meets West. Langenbecks Arch Surg 2021; 407:225-234. [PMID: 34825277 DOI: 10.1007/s00423-021-02370-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 10/27/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE To evaluate the prevalence and extension of macrovascular invasion (MaVI) in a large cohort of hepatocellular carcinoma (HCC) patients and analyze the association between MaVI and overall survival (OS). METHODS From 2011 to 2018, 2540 patients with newly diagnosed HCC who were managed in our institution were enrolled in this retrospective study. Tumor invasion of the intrahepatic branches of the portal or hepatic veins was defined as peripheral MaVI. Tumor invasion of the main portal vein or inferior vena cava was defined as central MaVI. RESULTS MaVI prevalence was 16.2% (n = 411). Among patients with Barcelona Clinic Liver Cancer (BCLC) stage C and Child-Pugh class A, 165 patients presented with peripheral MaVI and 89 patients with central MaVI. The median OS was 13.2 months (95% confidence interval [CI]: 11.4-15.4) in the peripheral MaVI group and 6.6 months (95% CI: 3.6-9.5) in the central MaVI group (p < 0.001). In patients with BCLC stage C and Child-Pugh class B or BCLC stage D, 68 patients presented with peripheral MaVI and 89 patients with central MaVI. The median OS was 3.6 months (95% CI: 3.1-4.2) in the peripheral MaVI group and 2.8 months (95% CI: 2.1-3.4) in the central MaVI group (p = 0.674). CONCLUSION The extension of MaVI significantly affected patient survival only in those with BCLC stage C and Child-Pugh class A. In patients with BCLC stage C and Child-Pugh class B or BCLC stage D, survival was poor irrespective of MaVI status.
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Affiliation(s)
- Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan.
| | - Wei-Feng Li
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
| | - Yu-Fan Cheng
- Liver Transplantation Center, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
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Kuo YH, Lu SN, Chen YY, Kee KM, Yen YH, Hung CH, Hu TH, Chen CH, Wang JH. Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis. Front Oncol 2021; 11:737767. [PMID: 34760699 PMCID: PMC8573180 DOI: 10.3389/fonc.2021.737767] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 10/04/2021] [Indexed: 12/12/2022] Open
Abstract
Background Lenvatinib is approved for patients with advanced hepatocellular carcinoma (HCC) due to its non-inferiority to sorafenib of overall survival (OR) in clinical trials. This study was to compare the effectiveness and safety of lenvatinib and sorafenib in the real world. Methods We retrospectively evaluated 338 patients with unresectable HCC who had undergone lenvatinib or sorafenib treatment between January 2018 and August 2020. Propensity-score matching analysis was performed with a 1:2 ratio to reduce the real-life baseline difference between the two groups. Results A total of 210 patients (Male/Female: 150/60, mean age: 65.8 years) were recruited including 70 patients in the Lenvatinib group and 140 patients in the Sorafenib group. Compared with sorafenib, lenvatinib had significantly longer progression-free survival (PFS) (5.2 vs 3.3 months, p=0.019) but similar OR (13.3 vs 11.8 months, p=0.714). Additionally, lenvatinib had better disease control rates (62.3 vs 48.6%, p=0.029) and equivalent incidences of treatment-related adverse events over sorafenib. In multivariate analysis, lenvatinib was associated with better PFS over sorafenib (hazard ratio: 0.49, 95% confidence interval: 0.3–0.79, p=0.004) after adjustments of albumin-bilirubin grade and alpha-fetoprotein level; however, different agents using lenvatinib or sorafenib did not contribute to OS, whether in univariate or multivariate analysis. Patients who failed lenvatinib had a lower proportion of having sequential systemic therapies compared with the Sorafenib group (36.2 vs 47.8%, p=0.02). The most frequently used sequential therapy following lenvatinib and sorafenib was chemotherapy (n=9, 42.8%) and regorafenib (n=33, 50.8%), respectively. Conclusions In clinical real-life practice, lenvatinib illustrated promising survival benefits and acceptable safety for patients with unresectable HCC, while reducing the risk of progression disease compared with sorafenib. Additionally, lack of approved post-lenvatinib systemic therapies is a serious issue in the real world.
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Affiliation(s)
- Yuan-Hung Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yen-Yang Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Kang H, Lee HW. Current role of systemic therapy in transarterial chemotherapy refractory hepatocellular carcinoma patients. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2021. [DOI: 10.18528/ijgii210046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Hansung Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Cantaloube M, Castan F, Creoff M, Prunaretty J, Bordeau K, Michalet M, Assenat E, Guiu B, Pageaux GP, Ychou M, Aillères N, Fenoglietto P, Azria D, Riou O. Image-Guided Liver Stereotactic Body Radiotherapy Using VMAT and Real-Time Adaptive Tumor Gating: Evaluation of the Efficacy and Toxicity for Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13194853. [PMID: 34638336 PMCID: PMC8507769 DOI: 10.3390/cancers13194853] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/15/2021] [Accepted: 09/20/2021] [Indexed: 12/25/2022] Open
Abstract
Simple Summary Although the use of stereotactic body radiation therapy (SBRT) in the management of hepatocellular carcinoma (HCC) remains unclear, it is a therapeutic option often considered in patients not eligible to or recurring after other local therapies. Liver SBRT can be delivered using a wide range of techniques and linear accelerators. We report the first evaluation for HCC of SBRT using volumetric modulated arc therapy (VMAT) and real-time adaptive tumor gating, which is a mainly completely non-invasive procedure (no fiducial markers for 65.2% of the patients). Our study showed that this SBRT technique has very favorable outcomes with optimal local control and a low toxicity rate. Abstract Liver SBRT is a therapeutic option for the treatment of HCC in patients not eligible for other local therapies. We retrospectively report the outcomes of a cohort of consecutive patients treated with SBRT for HCC at the Montpellier Cancer Institute. Between March 2013 and December 2018, 66 patients were treated with image-guided liver SBRT using VMAT and real-time adaptive tumor gating in our institute. The main endpoints considered in this study were local control, disease-free survival, overall survival, and toxicity. The median follow-up was 16.8 months. About 66.7% had prior liver treatment. Most patients received 50 Gy in five fractions of 10 Gy. No patient had local recurrence. Overall survival and disease-free survival were, respectively, 83.9% and 46.7% at one year. In multivariate analysis, the diameter of the lesions was a significant prognostic factor associated with disease-free survival (HR = 2.57 (1.19–5.53) p = 0.02). Regarding overall survival, the volume of PTV was associated with lower overall survival (HR = 2.84 (1.14–7.08) p = 0.025). No grade 3 toxicity was observed. One patient developed a grade 4 gastric ulcer, despite the dose constraints being respected. Image-guided liver SBRT with VMAT is an effective and safe treatment in patients with inoperable HCC, even in heavily pre-treated patients. Further prospective evaluation will help to clarify the role of SBRT in the management of HCC patients.
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Affiliation(s)
- Marie Cantaloube
- Montpellier Cancer Institute (ICM), University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France; (M.C.); (M.C.); (J.P.); (K.B.); (M.M.); (N.A.); (P.F.); (D.A.)
| | - Florence Castan
- Biometrics Unit ICM, Montpellier Cancer Institute, University Montpellier, 34298 Montpellier, France;
| | - Morgane Creoff
- Montpellier Cancer Institute (ICM), University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France; (M.C.); (M.C.); (J.P.); (K.B.); (M.M.); (N.A.); (P.F.); (D.A.)
- Oncodoc, 34500 Béziers, France
| | - Jessica Prunaretty
- Montpellier Cancer Institute (ICM), University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France; (M.C.); (M.C.); (J.P.); (K.B.); (M.M.); (N.A.); (P.F.); (D.A.)
| | - Karl Bordeau
- Montpellier Cancer Institute (ICM), University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France; (M.C.); (M.C.); (J.P.); (K.B.); (M.M.); (N.A.); (P.F.); (D.A.)
| | - Morgan Michalet
- Montpellier Cancer Institute (ICM), University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France; (M.C.); (M.C.); (J.P.); (K.B.); (M.M.); (N.A.); (P.F.); (D.A.)
| | - Eric Assenat
- Service d’Oncologie Médicale, CHU St Eloi, 34000 Montpellier, France;
| | - Boris Guiu
- Imagerie Médicale St Eloi, 34000 Montpellier, France;
| | | | - Marc Ychou
- Medical Oncology Department, Montpellier Cancer Institute (ICM), Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France;
| | - Norbert Aillères
- Montpellier Cancer Institute (ICM), University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France; (M.C.); (M.C.); (J.P.); (K.B.); (M.M.); (N.A.); (P.F.); (D.A.)
| | - Pascal Fenoglietto
- Montpellier Cancer Institute (ICM), University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France; (M.C.); (M.C.); (J.P.); (K.B.); (M.M.); (N.A.); (P.F.); (D.A.)
| | - David Azria
- Montpellier Cancer Institute (ICM), University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France; (M.C.); (M.C.); (J.P.); (K.B.); (M.M.); (N.A.); (P.F.); (D.A.)
| | - Olivier Riou
- Montpellier Cancer Institute (ICM), University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier University, INSERM U1194 IRCM, 34298 Montpellier, France; (M.C.); (M.C.); (J.P.); (K.B.); (M.M.); (N.A.); (P.F.); (D.A.)
- Correspondence:
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Khan AR, Wei X, Xu X. Portal Vein Tumor Thrombosis and Hepatocellular Carcinoma - The Changing Tides. J Hepatocell Carcinoma 2021; 8:1089-1115. [PMID: 34522691 PMCID: PMC8434852 DOI: 10.2147/jhc.s318070] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 08/13/2021] [Indexed: 12/12/2022] Open
Abstract
Portal vein involvement is considered one of the most fearful complications of hepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is associated with aggressive tumor biology (high grade), high tumor burden (number and size of lesions), high levels of serum markers (AFP), poor liver function (deranged LFT), and poor performance status of patients. The Barcelona Clinic Liver Cancer staging system places HCC patients with PVTT in advanced stage (BCLC Stage-C). This group contains a fairly heterogeneous patient population, previously considered candidates for palliative systemic therapy with sorafenib. However, this provided modest overall survival (OS) benefit. The results of a recent Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. While only lenvatinib proved to be non-inferior against sorafenib in a phase III (REFLECT trial), regorafenib (RESORCE trial), ramucirumab (REACH-2), and cabozantinib (CELESTIAL) have been approved second-line therapy in phase III clinical trials. Recently, the data on the prospect of other modalities in the management of HCC with PVTT is mounting with favorable results. Targeting multiple pathways in the HCC cascade using a combination of drugs and other modalities such as RT, TACE, TARE, and HAIC appear effective for systemic and loco-regional control. The quest for the ideal combination therapy and the sequence set is still widely unanswered and prospective trials are lacking. With the armament of available therapeutic options and the advances and refinements in the delivery system, down-staging patients to make them eligible for curative resection has been reported. In a rapidly evolving treatment landscape, performing surgery when appropriate, in the form of LR and even LT to achieve cure does not seem farfetched. Likewise, adjuvant therapy and prompt management of the recurrences holds the key to prolong OS and DFS. This review discusses the management options of HCC patients with PVTT.
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Affiliation(s)
- Abdul Rehman Khan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, People's Republic of China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, People's Republic of China
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Lee J, Han JW, Sung PS, Lee SK, Yang H, Nam HC, Yoo SH, Lee HL, Kim HY, Lee SW, Kwon JH, Jang JW, Kim CW, Nam SW, Oh JS, Chun HJ, Bae SH, Choi JY, Yoon SK. Comparative Analysis of Lenvatinib and Hepatic Arterial Infusion Chemotherapy in Unresectable Hepatocellular Carcinoma: A Multi-Center, Propensity Score Study. J Clin Med 2021; 10:4045. [PMID: 34575160 PMCID: PMC8464794 DOI: 10.3390/jcm10184045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/29/2021] [Accepted: 09/04/2021] [Indexed: 12/21/2022] Open
Abstract
The comparative efficacy and safety between lenvatinib and hepatic artery infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC) is still unclear. This multicenter historical cohort study enrolled 244 patients who were treated with HAIC (n = 173) or lenvatinib (n = 71) between 2012 and 2020. Propensity score matching (PSM) was performed, and 52 patients were selected per group. Clinical outcomes and safety were compared. Objective response rate (ORR) was not different between the two groups (26.0% vs. 23.1%, p = 0.736). Before PSM, the HAIC group had a higher proportion of Child-Pugh B and portal vein tumor, whereas the lenvatinib group had more patients with extrahepatic metastases, which was adjusted after PSM. There were no differences in progression-free survival (PFS) and overall survival (OS) after PSM (HAIC vs. lenvatinib, median PFS, 3.6 vs. 4.0 months, p = 0.706; median OS 10.8 vs. 7.9 months, p = 0.106). Multivariate Cox-regression showed that alpha-fetoprotein ≤1000 ng/mL was only an associated factor for OS after PSM in all patients (hazard ratio = 0.421, p = 0.011). Subgroup analysis for patients with a high tumor burden beyond the REFLECT eligibility criteria revealed that the HAIC group (n = 29) had a significantly longer OS than did the lenvatinib group (n = 30) (10.0 vs. 5.4 months, p = 0.004). More patients in the HAIC group achieved better liver function than those in the lenvatinib group at the time of best responses. There was no difference in the incidence of grade 3 and 4 adverse events between the two groups. Therefore, lenvatinib is comparable to HAIC in terms of ORR and OS in unresectable HCC meeting REFLECT eligibility criteria.
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Affiliation(s)
- Jaejun Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul 03382, Korea
| | - Ji-Won Han
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Pil-Soo Sung
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Soon-Kyu Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Hyun Yang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul 03382, Korea
| | - Hee-Chul Nam
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul 11765, Korea
| | - Sun-Hong Yoo
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 22711, Korea
| | - Hae-Lim Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 14647, Korea
| | - Hee-Yeon Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul 11765, Korea
| | - Sung-Won Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 14647, Korea
| | - Jung-Hyun Kwon
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 22711, Korea
| | - Jeong-Won Jang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Chang-Wook Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul 11765, Korea
| | - Soon-Woo Nam
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 22711, Korea
| | - Jung-Suk Oh
- Department of Radiology, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea; (J.-S.O.); (H.-J.C.)
| | - Ho-Jong Chun
- Department of Radiology, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea; (J.-S.O.); (H.-J.C.)
| | - Si-Hyun Bae
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul 03382, Korea
| | - Jong-Young Choi
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Seung-Kew Yoon
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (J.-W.H.); (S.-K.L.); (H.Y.); (H.-C.N.); (S.-H.Y.); (H.-L.L.); (H.-Y.K.); (S.-W.L.); (J.-H.K.); (J.-W.J.); (C.-W.K.); (S.-W.N.); (S.-H.B.); (J.-Y.C.); (S.-K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
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Liu CM, Huang BS, Yen YH, Wang YM, Huang EY, Hsu HC, Huang TT, Yang YH, Cheng JY. Concurrent Sorafenib and Radiotherapy versus Radiotherapy Alone for Locally Advanced Hepatocellular Carcinoma: A Propensity-Matched Analysis. J Hepatocell Carcinoma 2021; 8:963-973. [PMID: 34434903 PMCID: PMC8380802 DOI: 10.2147/jhc.s323302] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 07/31/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose Evidence is lacking concerning the benefit of the combination of sorafenib and radiotherapy to treat advanced hepatocellular carcinoma (HCC). To date, no publication has reported the outcomes of radiotherapy alone versus concurrent therapy. We aimed to compare the effectiveness of radiotherapy alone versus concurrent radiotherapy and sorafenib for locally advanced hepatocellular carcinoma. Materials and Methods We conducted a propensity score matching (PSM) cohort study comparing the effectiveness of the concurrent use of sorafenib and external beam radiotherapy versus radiotherapy alone in Barcelona Clinic Liver Cancer (BCLC) stage B or C, nonsurgically managed, nonmetastatic patients with HCC. Two subpopulations were matched based on baseline characteristics. Stratified analysis was also performed to assess the heterogeneous effects of the two arms. Overall survival (OS) was compared. Radiation-induced liver disease (RILD) and overt gastrointestinal (GI) bleeding events were also recorded. Results Seven hundred thirty-one BCLC stage B or C nonmetastatic HCC patients were identified from 2007 to 2017. Of these, 347 patients met the inclusion criteria (Radiotherapy alone: 269 patients; concurrent therapy: 78 patients). Propensity score matching yielded 73 patients each in the radiotherapy and concurrent groups. The median OS was 9.6 months in the radiotherapy-alone group and 9.9 months in the concurrent group (hazard ratio (HR): 1.12; 95% CI=0.78–1.62; p=0.544). Posttreatment toxicities, including radiation-induced liver disease and overt gastrointestinal bleeding, showed no significant differences between the groups. Conclusion In our study, the concurrent use of sorafenib and conventional external beam radiotherapy shows no survival benefit over radiotherapy alone for locally advanced hepatocellular carcinoma.
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Affiliation(s)
- Chieh-Min Liu
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Bing-Shen Huang
- Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.,Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Ming Wang
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.,School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Radiation Oncology, Xiamen Chang Gung Hospital, Fujian, People's Republic of China
| | - Eng-Yen Huang
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.,School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Radiation Oncology, Xiamen Chang Gung Hospital, Fujian, People's Republic of China
| | - Hsuan-Chih Hsu
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tzu-Ting Huang
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yao-Hsu Yang
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.,Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Jen-Yu Cheng
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Li CH, Palanisamy K, Li X, Yu SH, Wang IK, Li CY, Sun KT. Exosomal tumor necrosis factor-α from hepatocellular cancer cells (Huh-7) promote osteoclast differentiation. J Cell Biochem 2021; 122:1749-1760. [PMID: 34383347 DOI: 10.1002/jcb.30127] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 07/26/2021] [Accepted: 07/29/2021] [Indexed: 12/28/2022]
Abstract
Bone is the common extra-hepatic site for cancer metastasis. Hepatic cancer is associated with a higher incidence of pathological fracture. However, this important regulatory mechanism remains unexplored. Thus, exosome-mediated cell-cell communication between hepatocellular cancer and bone might be key to osteolytic bone destruction. Huh-7 exosomes were characterized for size and exosome marker expressions (CD63, Alix). Exosome mediated osteoclast differentiation in the RAW 264.7 cells was monitored from day 1 to 6 and multinucleated osteoclast formation and bone resorption activity were analyzed. The osteoclastogenic factor expressions in the exosomes and osteoclast differentiation markers such as tumor necrosis factor receptor 6 (TRAF6), nuclear factor κB (NF-κB), nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and cathepsin K (CTSK) were analyzed using western blot. Exosomes released by liver cancer cells (Huh-7) promoted osteoclast differentiation in RAW 264.7 cells. Analysis of osteoclastogenic factors in the exosomes showed that exosomes were specifically enriched with tumor necrosis factor α (TNF-α). Huh-7 exosomes promoted osteoclast differentiation by significantly increasing the number of TRAP-positive multi nucleated osteoclasts and resorption pits. Importantly, exosomes upregulated osteoclast markers TRAF6, NF-κB, and CTSK expressions. Further, neutralizing exosomal TNF-α reverted exosome-mediated osteoclast differentiation in RAW 264.7 cells. Collectively, our findings show that cellular communication of exosomal TNF-α from hepatocellular cancer cells (Huh-7) regulates osteoclast differentiation through NF-κB/CTSK/TRAP expressions. Thus, exosomal TNF-α might act as an important therapeutic target to prevent hepatocellular cancer mediated pathological bone disease.
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Affiliation(s)
- Ching-Hao Li
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Kalaiselvi Palanisamy
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Xin Li
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Shao-Hua Yu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan
| | - I-Kuan Wang
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,Division of Nephrology, China Medical University Hospital, Taichung, Taiwan.,Department of Internal Medicine, China Medical University, Taichung, Taiwan
| | - Chi-Yuan Li
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan
| | - Kuo-Ting Sun
- Department of Pediatric Dentistry, China Medical University Hospital, Taichung, Taiwan.,School of Dentistry, China Medical University, Taichung, Taiwan
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Lin CW, Chen YS, Lo GH, Wu TC, Yeh JH, Yeh ML, Dai CY, Huang JF, Chuang WL, Roberts L, Jun DW, Toyoda H, Yasuda S, Nguyen MH, Yu ML. Resubclassification and clinical management for Barcelona Clinic Liver Cancer Stage C hepatocellular carcinoma. Hepatol Int 2021; 15:946-956. [PMID: 34008091 DOI: 10.1007/s12072-021-10169-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 02/23/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma (HCC) can be markedly heterogeneous with varying prognosis. This study aims to establish a new subclassification system for BCLC-C HCC to better predict overall survival (OS) and to tailor therapy. METHODS We retrospectively studied 1856 BCLC-C HCC patients between 2006 and 2017 from E-Da Hospital, Taiwan (n = 622, training cohort), Kaohsiung Medical University Hospital, Taiwan (n = 774, Taiwan validation cohort), and Stanford University Medical Center and Mayo Clinic (United States), Hanyang University Hospital (South Korea), and Ogaki Municipal Hospital (Japan) to make up the international validation cohort (n = 460). RESULTS In the training cohort, significant factors associated with OS were largest tumor size ≥ 10 cm, extrahepatic spread, macrovascular invasion, and Child-Pugh class, which provided the basis, together with aged ≥ 75 years, for the substaging, through C0 to C4, of BCLC-C HCC patients. The median OS for substages C0, C1, C2, C3, and C4 were 43.8 months (95% confidence interval [CI] 32.2-53.7), 20.6 months (CI 14.1-25.9), 11.5 months (CI 8.02-14.1), 5.7 months (CI 4.02-5.98), and 3.2 months (CI 2.41-3.59), respectively, (p < 0.05). OS remained distinct among the proposed substages in the Taiwan validation cohort as well as the international validation cohort. The distinction between the substages persisted in subgroup analysis by substage combined with treatment modality. In substage C0-C3, patients receiving HCC curative therapy had a significantly better median OS than those receiving sorafenib or palliative therapy. CONCLUSION Our new substaging system provides more precise prognosis to better tailor therapy for BCLC-C HCC patients.
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Affiliation(s)
- Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- School of Chinese Medicine, College of Chinese Medicine, and Research Center for Traditional Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Yaw-Sen Chen
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Tsung-Chin Wu
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Jen-Hao Yeh
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Lewis Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Dae Won Jun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Chuang K, Wang S, Hsu S, Wang L. Impact of bromodomain-containing protein 4 (BRD4) and intestine-specific homeobox (ISX) expression on the prognosis of patients with hepatocellular carcinoma' for better clarity. Cancer Med 2021; 10:5545-5556. [PMID: 34173348 PMCID: PMC8366091 DOI: 10.1002/cam4.4094] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 05/26/2021] [Accepted: 06/05/2021] [Indexed: 12/18/2022] Open
Abstract
Epigenetic regulation is important for cancer tumor metastasis and progression, including lung and liver cancer. However, the mechanism of epigenetic regulation in liver cancer leaves much to be discussed. According to a previous study, p300/CBP-associated factor (PCAF) mediated epithelial-mesenchymal transition (EMT) and promotes cancer metastasis by recruiting intestine-specific homeobox (ISX) and bromodomain-containing protein 4 (BRD4) in lung cancer. To figure out whether the three genes are also expressed in patients with hepatocellular carcinoma (HCC) or not, and their correlation with patients' outcome, BRD4, PCAF, and ISX messenger RNA (mRNA) expression levels in 377 patients with HCC were investigated using quantitative polymerase chain reaction and confocal fluorescence imaging. The correlation of the gene expression (PCAF, ISX, and BRD4) in liver cancer is also being investigated. Here, we show that the mRNA expression of PCAF, BRD4, and ISX in 377 paired specimens from patients with HCC, and the adjacent normal tissues exhibited a tumor-specific expression pattern, highly correlated with disease pathogenesis, patient survival time, progression stage, and poor prognosis. The results show that ISX and BRD4 can potentially be a target for improving the survival rate.
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Affiliation(s)
- Kai‐Ting Chuang
- Graduate Institute of MedicineCollege of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
- School of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
| | - Shen‐Nien Wang
- Graduate Institute of MedicineCollege of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
- Division of General and Digestive SurgeryDepartment of SurgeryKaohsiung Medical University HospitalKaohsiungTaiwan
- Department of SurgeryCollege of MedicineKaohsiung Medical University HospitalKaohsiungTaiwan
- School of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
| | - Shih‐Hsien Hsu
- Graduate Institute of MedicineCollege of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
- Department of Medical ResearchKaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
| | - Li‐Ting Wang
- Department of Life ScienceNational Taiwan Normal UniversityTaipeiTaiwan
- Center of Applied GenomicsKaohsiung Medical UniversityKaohsiungTaiwan
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Hepatic Arterial Infusion Chemotherapy Followed by Lipiodol Infusion for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Single-Center Experience. ACTA ACUST UNITED AC 2021; 57:medicina57080779. [PMID: 34440985 PMCID: PMC8399970 DOI: 10.3390/medicina57080779] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 07/27/2021] [Accepted: 07/28/2021] [Indexed: 12/21/2022]
Abstract
Background and Objectives: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) followed by lipiodol infusion in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Materials and Methods: Thirty-two patients with advanced HCC and PVTT who received HAIC with regimens of cisplatin, mitomycin-C, and 5-fluorouracil followed by lipiodol infusion were enrolled. The primary efficacy endpoint was tumor response rate. The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was used for assessment of treatment response. The secondary endpoints were overall survival (OS) and progression free survival (PFS). Prognostic factors for survival also were evaluated. Results: The median OS and PFS were 11.9 and 9.5 months, respectively. Seventeen patients (53.1%) achieved objective response, and 23 patients (71.9%) achieved disease control. The length of survival in the responder and disease control groups was longer than in the non-responder and progressive disease groups after two cycles of HAIC (responder vs. non-responder: 16.5 vs. 7.9 months, p = 0.001; disease control vs. progressive disease: 12.3 vs. 5.6 months, p < 0.001) and after completing HAIC (responder vs. non-responder: 15.7 vs. 6.9 months, p = 0.001; disease control vs. progressive disease: 13.6 vs. 6.9 months, p < 0.001). Better survival was associated with Child-Pugh A liver function (p = 0.013), with early response to two HAIC cycles (p = 0.009), and with response (p = 0.02) and disease control (p = 0.001) after completing HAIC treatment. Conclusion: HAIC followed by lipiodol infusion is a safe and feasible treatment for advanced HCC with PVTT. Patients with early response could continue HAIC treatment with expected prolonged survival.
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Romano F, Chiarelli M, Garancini M, Scotti M, Zago M, Cioffi G, De Simone M, Cioffi U. Rethinking the Barcelona clinic liver cancer guidelines: Intermediate stage and Child-Pugh B patients are suitable for surgery? World J Gastroenterol 2021; 27:2784-2794. [PMID: 34135554 PMCID: PMC8173387 DOI: 10.3748/wjg.v27.i21.2784] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 02/24/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023] Open
Abstract
According to Barcelona Clinic Liver Cancer recommendations, intermediate stage hepatocellular carcinomas (stage B) are excluded from liver resection and are referred to palliative treatment. Moreover, Child-Pugh B patients are not usually candidates for liver resection. However, many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection, maintaining that hepatic resection is not contraindicated in selected patients with non-early-stage hepatocellular carcinoma and without normal liver function. Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification, and this treatment gives good results in the setting of multinodular, large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis. In this review we explore this controversial topic, and we show through the literature analysis how liver resection may improve the short- and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients. However, other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.
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Affiliation(s)
- Fabrizio Romano
- Department of Surgery, School of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Marco Chiarelli
- Emergency and Robotic Surgery, A. Manzoni Hospital, ASST Lecco, Lecco 23900, Italy
| | - Mattia Garancini
- Department of General Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Mauro Scotti
- Department of General Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Mauro Zago
- Emergency and Robotic Surgery, A. Manzoni Hospital, ASST Lecco, Lecco 23900, Italy
| | - Gerardo Cioffi
- Department of Sciences and Technologies, Università degli Studi del Sannio di Benevento, Benevento 82100, Italy
| | | | - Ugo Cioffi
- Department of Surgery, University of Milan, Milano 20122, Italy
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Tsai MC, Lin CC, Chen DW, Liu YW, Wu YJ, Yen YH, Huang PY, Yao CC, Chuang CH, Hsiao CC. The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy. ACTA ACUST UNITED AC 2021; 57:medicina57060574. [PMID: 34199695 PMCID: PMC8229727 DOI: 10.3390/medicina57060574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/26/2021] [Accepted: 06/02/2021] [Indexed: 01/27/2023]
Abstract
Background and Objectives: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. Materials and Methods: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. Results: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, p = 0.006), α-fetoprotein (AFP) (HR, 1.696, p = 0.003), liver cirrhosis (HR, 1.735, p = 0.002), and advanced TNM stage (HR, 2.061, p < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, p < 0.001) and histological grade (HR, 2.675, p = 0.002) and high PAR2 expression (HR, 1.832, p = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. Conclusion: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.
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Affiliation(s)
- Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (M.-C.T.); (Y.-H.Y.); (P.-Y.H.); (C.-C.Y.)
- Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (C.-C.L.); (Y.-W.L.); (Y.-J.W.)
| | - Ding-Wei Chen
- Center for Translational Research in Biomedical Sciences, Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;
| | - Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (C.-C.L.); (Y.-W.L.); (Y.-J.W.)
| | - Yi-Ju Wu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (C.-C.L.); (Y.-W.L.); (Y.-J.W.)
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (M.-C.T.); (Y.-H.Y.); (P.-Y.H.); (C.-C.Y.)
| | - Pao-Yuan Huang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (M.-C.T.); (Y.-H.Y.); (P.-Y.H.); (C.-C.Y.)
| | - Chih-Chien Yao
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (M.-C.T.); (Y.-H.Y.); (P.-Y.H.); (C.-C.Y.)
| | - Ching-Hui Chuang
- Department of Nursing, Meiho University, Pingtung 91202, Taiwan;
| | - Chang-Chun Hsiao
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
- Correspondence: ; Tel.: +886-7-7317123 (ext. 8979) or +886-955906053; Fax: +886-7-7311696
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Real-time virtual sonography-assisted radiofrequency ablation in liver tumors with conspicuous or inconspicuous images or peritumoral landmarks under ultrasonography. Abdom Radiol (NY) 2021; 46:2814-2822. [PMID: 33388803 PMCID: PMC8205891 DOI: 10.1007/s00261-020-02875-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 11/08/2020] [Accepted: 11/18/2020] [Indexed: 02/08/2023]
Abstract
Objectives The objectives of this study were to determine the primary technique effectiveness (PTE), to compare the complete response and local recurrence rates between conspicuous and inconspicuous tumors using single and switching electrodes of real-time virtual sonography (RVS)-assisted radiofrequency ablation (RFA) in conspicuous and inconspicuous hepatic tumors under conventional ultrasonography (US). Subjects and method We compared the complete ablation of inconspicuous tumors with and without anatomical landmark (N = 54) with conspicuous liver tumors (N = 272). Conventional US imaging was done initially, and then these images were fused with CT or MRI arterial-venous-wash-out cross-sectional studies and synchronized with real-time US images. Results RVS-assisted RFA was technically feasible in all patients. The PTE rate after the first ablation was 94% (245/261) for conspicuous tumors, 88% (7/8) in inconspicuous tumors with landmark, and 78% (36/46) in inconspicuous tumors without landmark. The complete response (p = 0.1912 vs. p = 0.4776) and local recurrence rate (p = 0.1557 vs. p = 0.7982) were comparable in conspicuous tumors of both HCC and liver metastasis group when single or multiple switching was used. The cumulative local recurrence in the conspicuous and inconspicuous tumors of the HCC group (p = 0.9999) was almost parallel after 12 (10% vs. 4%) and 24 (13% vs. 4%) months of follow-up. In the liver metastasis group, the cumulative local recurrence for conspicuous tumors (p = 0.9564) was nearly equal after 12 and 24 months of monitoring (24% vs. 27%) while no recurrence was incurred for the inconspicuous tumors. Conclusion RVS-assisted RFA is an effective tool for the treatment of conspicuous and inconspicuous HCC and hepatic metastasis.
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Kuo SC, Lin CN, Lin YJ, Chen WY, Hwang JS, Wang JD. Optimal Intervals of Ultrasonography Screening for Early Diagnosis of Hepatocellular Carcinoma in Taiwan. JAMA Netw Open 2021; 4:e2114680. [PMID: 34165580 PMCID: PMC8226422 DOI: 10.1001/jamanetworkopen.2021.14680] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
IMPORTANCE There are different clinical practices regarding ultrasonography screening intervals for hepatocellular carcinoma (HCC) despite recommendations from international guidelines. OBJECTIVE To evaluate whether ultrasonography screening using intervals suggested by international guidelines is associated with cancer stage shifting, reductions in mortality, and improved quality of life (QoL) for patients with HCC. DESIGN, SETTING, AND PARTICIPANTS This nationwide comparative effectiveness research study estimated lifetime survival functions using interlinkages of 3 databases from Taiwan-the Taiwan National Health Insurance, Taiwan National Cancer Registry, and National Mortality Registry-combined with QoL measurements obtained from National Cheng Kung University Hospital. In total, 114 022 patients listed as having newly diagnosed HCC from 2002 through 2015 in the Taiwan National Cancer Registry were followed up until 2017. The QoL values of 1059 patients with HCC who visited National Cheng Kung University Hospital were prospectively measured with the European QoL-5 dimensions questionnaire from 2011 through 2019. Patients were categorized based on the time between their last ultrasonography screening and the index date (90 days prior to HCC diagnosis) as 1 of 5 subcohorts: 6 months (0-6 months), 12 months (7-12 months), 24 months (13-24 months), 36 months (25-36 months), and longer than 36 months (no screening in the previous 3 years). Data were analyzed from April 2020 to April 2021. MAIN OUTCOMES AND MEASURES Life expectancy, quality-adjusted life expectancy, and loss of life expectancy or loss of quality-adjusted life expectancy compared with age-, sex-, and calendar year-matched cohorts. RESULTS There were 59 194 patients with Barcelona Clinic Liver Cancer staging information, including 42 081 men (mean [SD] age, 62.2 [12.6] years) and 17 113 women (mean [SD] age, 69.0 [11.2] years). There was a consistent trend showing that the longer the interval between ultrasonography examinations, the higher the loss of life expectancy and loss of quality-adjusted life expectancy for both sexes. Loss of quality-adjusted life expectancy values for male subcohorts were 10.0 (95% CI, 9.1-10.9) quality-adjusted life-years (QALYs) for ultrasonography screening intervals of 6 months, 11.1 (95% CI, 10.4-11.8) QALYs for 12 months, 12.1 (95% CI, 11.5-12.7) QALYs for 24 months, 13.1 (95% CI, 12.6-13.6) QALYs for 36 months, and 14.6 (95% CI, 14.2-15.0) QALYs for longer than 36 months. Loss of quality-adjusted life expectancy values for female subcohorts were 9.0 (95% CI, 8.3-9.6) QALYs for 6 months, 9.7 (95% CI, 9.2-10.2) QALYs for 12 months, 10.3 (95% CI, 9.8-10.7) QALYs for 24 months, 10.7 (95% CI, 10.2-11.1) QALYs for 36 months, and 11.4 (95% CI, 11.0-11.8) QALYs for longer than 36 months. Patients with underlying hepatitis B virus infection or cirrhosis had the greatest improvement in life expectancy with shorter screening intervals. CONCLUSIONS AND RELEVANCE Regular ultrasonography screening with intervals less than 6 to 12 months may be associated with early detection of HCC, save lives, and improve the quality of life for patients with HCC from a lifetime perspective.
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Affiliation(s)
- Shih-Chiang Kuo
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Ni Lin
- Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wei-Ying Chen
- Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | | | - Jung-Der Wang
- Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Chen LC, Lin HY, Hung SK, Chiou WY, Lee MS. Role of modern radiotherapy in managing patients with hepatocellular carcinoma. World J Gastroenterol 2021; 27:2434-2457. [PMID: 34092968 PMCID: PMC8160620 DOI: 10.3748/wjg.v27.i20.2434] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/16/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Several treatment options are available for managing HCC patients, classified roughly as local, local-regional, and systemic therapies. The high post-monotherapy recurrence rate of HCC urges the need for the use of combined modalities to increase tumor control and patient survival. Different international guidelines offer treatment recommendations based on different points of view and classification systems. Radiotherapy (RT) is a well-known local-regional treatment modality for managing many types of cancers, including HCC. However, only some of these treatment guidelines include RT, and the role of combined modalities is rarely mentioned. Hence, the present study reviewed clinical evidence for the use of different combined modalities in managing HCC, focusing on modern RT's role. Modern RT has an increased utility in managing HCC patients, mainly due to two driving forces. First, technological advancement (e.g., stereotactic body radiotherapy and advanced proton-beam therapy) enables precise delivery of radiation to increase tumor control and reduce side effects in the surrounding normal tissue. Second, the boom in developing target therapies and checkpoint-blockade immunotherapy prolongs overall survival in HCC patients, re-emphasizing the importance of local tumor control. Remarkably, RT combines with systemic therapies to generate the systemic therapy augmented by radiotherapy effect, a benefit now being actively investigated.
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Affiliation(s)
- Liang-Cheng Chen
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
| | - Hon-Yi Lin
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
- Institute of Molecular Biology, National Chung Cheng University, Min-Hsiung, Chia-Yi 62102, Taiwan
| | - Shih-Kai Hung
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
| | - Wen-Yen Chiou
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
| | - Moon-Sing Lee
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
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Lee CW, Yu MC, Wang CC, Lee WC, Tsai HI, Kuan FC, Chen CW, Hsieh YC, Chen HY. Liver resection for hepatocellular carcinoma larger than 10 cm: A multi-institution long-term observational study. World J Gastrointest Surg 2021; 13:476-492. [PMID: 34122737 PMCID: PMC8167847 DOI: 10.4240/wjgs.v13.i5.476] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/13/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The treatment of hepatocellular carcinoma (HCC) ≥ 10 cm remains a challenge. AIM To consolidate the role of surgical resection for HCC larger than 10 cm. METHODS Eligible HCC patients were identified from the Chang Gung Research Database, the largest multi-institution database, which collected medical records of all patients from Chang Gung Memorial Foundation. The surgical outcome of HCC ≥ 10 cm (L-HCC) was compared to that of HCC < 10 cm (S-HCC) (model 1). The survival of L-HCC after either liver resection or transarterial chemoembolization (TACE) was also analyzed (model 2). The long-term risks of all-cause mortality and recurrence were assessed to consolidate the role of surgery for L-HCC. RESULTS From January 2004 to July 2015, a total of 32403 HCC patients were identified from the Chang Gung Research Database. Among 3985 patients who received liver resection, 3559 (89.3%) had S-HCC, and 426 had L-HCC. The L-HCC patients had a worse disease-free survival (0.27 for L-HCC vs 0.40 for S-HCC) and overall survival (0.18 for L-HCC vs 0.45 for S-HCC) than the S-HCC after liver resection (both P < 0.001). However, the surgical and long-term outcome of resected L-HCC had improved dramatically in the recent decades. After adjusting for covariates, surgery could provide a better outcome for L-HCC than TACE (adjusted hazard ratio of all-cause mortality: 0.46, 95% confidence interval: 0.38-0.56 for surgery). Subgroup analysis stratified by different stages showed similar trend of survival benefit among L-HCC patients receiving surgery. CONCLUSION Our study demonstrated an improving surgical outcome for HCC larger than 10 cm. Under selected conditions, surgery is better than TACE in terms of disease control and survival and should be performed. Due to inferior survival, a subclassification within T1 stage should be considered. Future studies are mandatory to confirm our findings.
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Affiliation(s)
- Chao-Wei Lee
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Guishan 333, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Guishan 333, Taoyuan, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan 333, Taoyuan, Taiwan
| | - Ming-Chin Yu
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Guishan 333, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Guishan 333, Taoyuan, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan 333, Taoyuan, Taiwan
- Department of Surgery, New Taipei Municipal Tu-Cheng Hospital (Built and Operated by Chang Gung Medical Foundation), Tu-Cheng 236017, New Taipei City, Taiwan
| | - Chih-Chi Wang
- Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- Division of General Surgery, Department of Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Wei-Chen Lee
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Guishan 333, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Guishan 333, Taoyuan, Taiwan
| | - Hsin-I Tsai
- College of Medicine, Chang Gung University, Guishan 333, Taoyuan, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan 333, Taoyuan, Taiwan
- Department of Anesthesiology, Linkou Chang Gung Memorial Hospital, Guishan 333, Taoyuan, Taiwan
| | - Feng-Che Kuan
- Department of Hematology and Oncology, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Chun-Wei Chen
- College of Medicine, Chang Gung University, Guishan 333, Taoyuan, Taiwan
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Guishan 333, Taoyuan, Taiwan
| | - Yi-Chung Hsieh
- College of Medicine, Chang Gung University, Guishan 333, Taoyuan, Taiwan
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Guishan 333, Taoyuan, Taiwan
| | - Hsing-Yu Chen
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan 333, Taoyuan, Taiwan
- Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Taoyuan Chang Gung Memorial Hospital, Guishan 33378, Taoyuan, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Guishan 333, Taoyuan, Taiwan
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