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1
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Xing S, Zhang H, Hou Z, Peng F, Liu L, Wang D, Ge N, Liu X. NIR-triggered arsenic-loaded layered double hydroxide-based films for localized thermal synergistic chemotherapy. J Colloid Interface Sci 2024; 675:857-869. [PMID: 39002236 DOI: 10.1016/j.jcis.2024.07.038] [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: 04/16/2024] [Revised: 07/03/2024] [Accepted: 07/05/2024] [Indexed: 07/15/2024]
Abstract
Portal vein tumor thrombus (PVTT) formed by cancer cell invasion is a major cause of high mortality in hepatocellular carcinoma (HCC), and the formation of thrombus will be accelerated by bacterial colonization on the surface of the implant after surgery. In this work, Polypyrrole-coated arsenic-loaded layered double hydroxide films were in situ constructed on the nickel-titanium alloy for the efficient killing of tumour cells by thermo-therapeutic synergistic chemotherapy. The good near-infrared photothermal conversion ability of polypyrrole enables the sample surface temperature to be raised to about 51 °C at a low photothermal power (0.5 w/cm2), while the elevated temperature could further accelerate the release of drug arsenic. In addition, when NIR light is not applied, the polypyrrole coating also cleverly acts as a "barrier layer" to reduce the natural release of arsenic in normal tissues to avoid toxicity issues. In vivo and in vitro experiments have demonstrated that the platform exhibits excellent antitumor and antibacterial abilities. In contrast to the systemic toxicity issues associated with systemic circulation of nanotherapeutic drugs, this in situ functional film is expected to be used in localised interventions for precise drug delivery, and is also more suitable for surgical treatment scenarios in PVTT surgeries.
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Affiliation(s)
- Shun Xing
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Haifeng Zhang
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China; School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou 310024, China
| | - Zhenhao Hou
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Feng Peng
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Lidan Liu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Donghui Wang
- School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin 300130, China
| | - Naijian Ge
- Intervention Center, Eastern Hepatobiliary Surgery Hospital, the Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China.
| | - Xuanyong Liu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China; School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou 310024, China.
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Li Y, Fan N, He X, Zhu J, Zhang J, Lu L. Research Progress in Predicting Hepatocellular Carcinoma with Portal Vein Tumour Thrombus in the Era of Artificial Intelligence. J Hepatocell Carcinoma 2024; 11:1429-1438. [PMID: 39050809 PMCID: PMC11268770 DOI: 10.2147/jhc.s474922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 06/24/2024] [Indexed: 07/27/2024] Open
Abstract
Hepatocellular Carcinoma (HCC) is a condition associated with significant morbidity and mortality. The presence of Portal Vein Tumour Thrombus (PVTT) typically signifies advanced disease stages and poor prognosis. Artificial intelligence (AI), particularly Machine Learning (ML) and Deep Learning (DL), has emerged as a promising tool for extracting quantitative data from medical images. AI is increasingly integrated into the imaging omics workflow and has become integral to various medical disciplines. This paper provides a comprehensive review of the mechanisms underlying the formation and progression of PVTT, as well as its impact on clinical management and prognosis. Additionally, it outlines the advancements in AI for predicting the diagnosis of HCC and the development of PVTT. The limitations of existing studies are critically evaluated, and potential future research directions in the realm of imaging for the diagnostic prediction of HCC and PVTT are discussed, with the ultimate goal of enhancing survival outcomes for PVTT patients.
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Affiliation(s)
- Yaduo Li
- Medical Imaging Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of China
| | - Ningning Fan
- Medical Imaging Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of China
| | - Xu He
- Department of Interventional Medicine, Guangzhou First People’s Hospital, Guangzhou, People’s Republic of China
| | - Jianjun Zhu
- R&D Department, Hanglok-Tech Co., Ltd., Hengqin, People’s Republic of China; Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China
| | - Jie Zhang
- Medical Imaging Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of China
| | - Ligong Lu
- Medical Imaging Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of China
- Department of Interventional Medicine, Guangzhou First People’s Hospital, Guangzhou, People’s Republic of China
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Gavriilidis P, Pawlik TM, Azoulay D. Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus: State of art and future perspectives. Hepatobiliary Pancreat Dis Int 2024; 23:221-227. [PMID: 37903712 DOI: 10.1016/j.hbpd.2023.10.009] [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: 03/15/2023] [Accepted: 10/18/2023] [Indexed: 11/01/2023]
Abstract
BACKGROUND Despite advances in the diagnosis of patients with hepatocellular carcinoma (HCC), 70%-80% of patients are diagnosed with advanced stage disease. Portal vein tumor thrombus (PVTT) is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated. DATA SOURCES A systematic search of MEDLINE (PubMed), Embase, Cochrane Library and Database for Systematic Reviews (CDSR), Google Scholar, and National Institute for Health and Clinical Excellence (NICE) databases until December 2022 was conducted using free text and MeSH terms: hepatocellular carcinoma, portal vein tumor thrombus, portal vein thrombosis, vascular invasion, liver and/or hepatic resection, liver transplantation, and systematic review. RESULTS Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy. Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus, accurate identification of the subgroups of patients who may benefit from resection, as well as meticulous surgical technique. This review addressed five specific areas: (a) formation of PVTT; (b) classifications of PVTT; (c) controversies related to clinical guidelines; (d) surgical treatments versus non-surgical approaches; and (e) characterization of surgical techniques correlated with classifications of PVTT. CONCLUSIONS Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.
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Affiliation(s)
- Paschalis Gavriilidis
- Department of Surgery, Colchester General Hospital, Turner Road, Colchester CO4 5JL, UK.
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA
| | - Daniel Azoulay
- Department of Hepato-Biliary and Liver Transplantation surgery, Paul Brousse University Hospital, Paris-Saclay University, Villejuif 94800, France
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Guo Y, Tian S, Zhan N, Liu C, Li J, Hu J, Qiu M, Huang B, Dong W. Ascitic microbiota alteration is associated with portal vein tumor thrombosis occurrence and prognosis in hepatocellular carcinoma. mBio 2024; 15:e0024524. [PMID: 38564690 PMCID: PMC11077998 DOI: 10.1128/mbio.00245-24] [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: 01/26/2024] [Accepted: 03/05/2024] [Indexed: 04/04/2024] Open
Abstract
Portal vein tumor thrombosis (PVTT) frequently leads to malignant ascites (MA) in individuals with hepatocellular carcinoma (HCC), remaining a bottleneck in the treatment. This study aimed to explore the differences in microbes in paired groups and provide novel insights into PVTT and MA-related treatments. Formalin-fixed paraffin embedding ascite samples were collected from MA secondary to HCC and benign ascites (BA) secondary to liver cirrhosis (LC). Ascitic microbiota profiles were determined in the HCC and LC groups by 16S rRNA sequencing. Prognostic risk factors were screened using survival analysis. The correlation between the significantly different microbial signatures in the groups with PVTT (WVT) and non-PVTT (NVT) and clinical characteristics was explored. The expression of different immune cells was determined by labeling four markers in the MA tissue chips using multiplex immunohistochemistry. A total of 240 patients (196 with HCC with MA and 44 with LC with BA) were included in this study. Microbial profiles differed between the HCC and LC groups. PVTT and Barcelona Clinic Liver Cancer stage were shown to be prognostic risk factors. Significant differences in the alpha and beta diversities were observed between the WVT and NVT groups. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC MA. Differences in microbial signatures between the WVT and NVT groups were correlated with the level of C-reactive protein and apolipoprotein A1. This study revealed the microbial differences in the tumor microenvironment of MA secondary to HCC and BA secondary to LC.IMPORTANCEFirst, we explored the alteration of the ascites ecosystem through the microbiota in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Second, this is the first clinical study to investigate the differences between patients with HCC with and without portal vein tumor thrombosis via 16S rRNA sequencing. These results revealed a decreased microbial diversity and metabolic dysregulation in individuals with HCC and portal vein tumor thrombosis. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC malignant ascitic fluid. Our study provides a new perspective on treating malignant ascites secondary to HCC.
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Affiliation(s)
- Yingyun Guo
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Shan Tian
- Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Na Zhan
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chuan Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jiao Li
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jiaming Hu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Meiqi Qiu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Binglu Huang
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Weiguo Dong
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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Xue T, Yu H, Feng W, Wang Y, Wu S, Wang L, Zhu P, Guan J, Sun Q. Efficacy and Safety of Hepatic Arterial Infusion Therapy with Cinobufacini in Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Retrospective Cohort Study. Cancer Manag Res 2024; 16:163-175. [PMID: 38505102 PMCID: PMC10948332 DOI: 10.2147/cmar.s440017] [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: 10/27/2023] [Accepted: 02/17/2024] [Indexed: 03/21/2024] Open
Abstract
Background The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI. Methods The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups. Results The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, P=0.048), the median OS (14.8 months vs 11.1 months, P=0.010), and the median PFS (10.3 months vs 6.0 months, P=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, P=0.043) and Vp3 (15.0 months vs 11.4 months, P=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, P=0.028) and Vp3 (10.8 months vs 6.6 months, P=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40-0.91; P=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03-2.16; P=0.032) and AFP (>1000; HR, 1.61; 95% CI: 1.08-1.91; P=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, P=0.009). Conclusion Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.
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Affiliation(s)
- Tao Xue
- Clinical Research Center, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China
| | - Hongbin Yu
- Department of Hepatobiliary Surgery, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China
| | - Wenming Feng
- Department of Hepatobiliary Surgery, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China
| | - Yao Wang
- Department of Hepatobiliary Surgery, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China
| | - Shiyong Wu
- Department of Radiology, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China
| | - Lili Wang
- Department of Nursing, Physical Examination Center of Aishan, Huzhou, People’s Republic of China
| | - Peiqin Zhu
- Department of Internal Medicine, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou, People’s Republic of China
| | - Jianming Guan
- Department of Ultrasound, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China
- Department of Ultrasound, Mingzhou Hospital, Huzhou, People’s Republic of China
| | - Quan Sun
- Laboratory of Blood Transfusion Research, Huzhou Center Blood Station, Huzhou, People’s Republic of China
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Lu H, Zheng C, Liang B, Xia X, Fan H. Efficacy and safety analysis of TACE + PEI + lenvatinib compared with TACE + lenvatinib for the treatment of hepatocellular carcinoma with PVTT: a retrospective study. Front Oncol 2024; 14:1280837. [PMID: 38298738 PMCID: PMC10827889 DOI: 10.3389/fonc.2024.1280837] [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: 08/21/2023] [Accepted: 01/03/2024] [Indexed: 02/02/2024] Open
Abstract
Objective The aim of this study was to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection (PEI) and lenvatinib in HCC patients with PVTT (Vp2-3), thus providing a safe and effective treatment strategy for advanced HCC patients. Materials and methods Clinical data of 227 patients with unresectable HCC and PVTT treated at the Union Hospital from January 2018 to December 2021 were retrospectively analyzed. The patients were divided into two groups according to their treatment methods: TACE+PEI+lenvatinib group (N=103) and TACE+lenvatinib group (N=124). Results The proportion of patients with disappearance, shrinkage, or no change of PVTT after treatment was significantly higher in the TACE+PEI+lenvatinib group compared to the TACE+lenvatinib group, with statistical significance (P<0.001). The TACE+PEI+lenvatinib group had higher objective response rate (ORR) (50.5% vs. 25.8%, P<0.001) and disease control rate (DCR) (87.4% vs. 74.2%, P=0.013) than the TACE+lenvatinib group. The median progression-free survival (mPFS) of the TACE+PEI+lenvatinib group was longer than that of the TACE+lenvatinib group (8.1 months vs. 6.5 months, P<0.001). Consistently, the median overall survival (mOS) of the TACE+PEI+lenvatinib group was longer than that of the TACE+lenvatinib group (17.1 months vs. 13.9 months, P<0.001). Conclusion Among HCC patients with PVTT (Vp2-3), TACE+PEI+lenvatinib is more effective comparing to TACE+lenvatinib in prolonging PFS and OS. The control of PVTT in the TACE+PEI+lenvatinib group was significantly more satisfactory than that in the TACE+lenvatinib group. TACE+PEI+lenvatinib is a safe and effective treatment strategy for HCC patients with PVTT (Vp2-3).
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Affiliation(s)
- Haohao Lu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xiangwen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Hongjie Fan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
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Liu B, Liu J, Mei X, Zhang ZQ, Fang J, Zhou LL, Zheng JL, Lin HY, Zhu XL, Li DL. Pretreatment Non-Invasive Biomarkers as Predictors to Estimate Portal Vein Tumor Thrombosis (PVTT) Risk and Long-Term Survival in HBV-Related Hepatocellular Carcinoma Patients Without PVTT. J Hepatocell Carcinoma 2023; 10:2367-2382. [PMID: 38164511 PMCID: PMC10758161 DOI: 10.2147/jhc.s442487] [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: 09/28/2023] [Accepted: 12/19/2023] [Indexed: 01/03/2024] Open
Abstract
Background PVTT is a hallmark of advanced hepatocellular carcinoma (HCC). We aim to explore the influence of non-invasive biomarkers on the occurrence of PVTT and develop and validate models for predicting prognosis in HBV-related HCC patients without PVTT. Methods A total of 1026 HBV-related HCC patients without PVTT were enrolled, with 515 in the training cohort, 216 in the internal validation cohort, and 295 in the external validation cohort. We conducted Cox regression analyses to discern the independent risk factors associated with PVTT events, PFS, and OS, then constructed and validated predictive models. The predictive and discriminatory capabilities of models were assessed using the calibration, time-dependent ROC, and DCA curves. Results In our study, 136 patients (13.3%) experienced PVTT events during the follow-up period. The Cox regression analysis unveiled that male gender, AAPR ≤0.49, APRI >0.48, extrahepatic metastasis, and multiple tumors were independent risk factors for PVTT. In the training cohort, non-invasive biomarkers (AAR and APRI), AFP, ascites, and tumor-related characteristics (extrahepatic metastasis, tumor diameter, tumor number, and PVTT event) were independent risk factors for both OS and PFS, whereas age and ALBI grade independently correlated with OS. The C-indexes of OS and PFS nomogram models were 0.795 and 0.733 in the training cohort, 0.765 and 0.716 in the internal validation cohort, and 0.780 and 0.722 in the external validation cohort, respectively. Our models demonstrated strong predictive and discriminative abilities in all cohorts and yielded a greater net benefit compared to three traditional staging systems. Conclusion Non-invasive biomarkers are expected to be reliable predictors for assessing PVTT risk and predicting prognosis among HBV-related HCC patients without PVTT.
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Affiliation(s)
- Bang Liu
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People’s Republic of China
- Department of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China
| | - Jia Liu
- Department of Hepatobiliary Surgery, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China
| | - Xuan Mei
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People’s Republic of China
| | - Zhi-Qiang Zhang
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People’s Republic of China
- Department of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China
| | - Jian Fang
- Department of Hepatobiliary Medicine, The Third Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, People’s Republic of China
| | - Li-Li Zhou
- Department of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China
| | - Jiao-Long Zheng
- Department of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China
| | - Hai-Yan Lin
- Department of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China
| | - Xiu-Ling Zhu
- Department of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China
| | - Dong-Liang Li
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People’s Republic of China
- Department of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China
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Jiao T, Tang H, Zhang W, Hu B, Wan T, Cao Y, Zhang Z, Wang Y, Cao J, Cui M, Lu S. Long-term survival and portal vein patency with novel PVTT surgery approach in advanced HCC patients with Vp3/4 PVTT following combination therapy of TKIs and PD-1 inhibitors. BMC Surg 2023; 23:384. [PMID: 38114938 PMCID: PMC10731777 DOI: 10.1186/s12893-023-02291-1] [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: 07/15/2023] [Accepted: 12/08/2023] [Indexed: 12/21/2023] Open
Abstract
BACKGROUND It is controversial whether patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) should undergo salvage surgery following the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein 1 (PD-1) inhibitors. This study aimed to elucidate the efficiency and safety of salvage surgery following combination therapy, while also summarizing a novel surgical approach for Vp3/4 PVTT. METHODS Between April 2019 and December 2022, a consecutive series of unresectable HCC patients with PVTT who received salvage surgery following combination therapy were enrolled. Evaluation included perioperative and long-term follow-up outcomes. The complete removal of Vp3/4 PVTT was achieved using a novel surgical approach characterized by "longitudinal incision and transverse suturing" and "angle-to-straight conversion". RESULTS Forty patients including 22 patients with Vp3 and 18 patients with Vp4 were included. Long-term follow-up showed similar rates of portal vein patency (Vp3: 95.5%, Vp4:94.4%, p = 0.900), and 3-year portal vein patency rates were 95.0%. There were no significant differences observed in combination therapy-related adverse events (p = 0.253) and perioperative complications (p = 0.613) between the Vp3 and Vp4 groups. The recurrence patterns were similar between the two groups (p = 0.131). There were no significant differences in overall survival (OS) and recurrence-free (RFS) survival between the Vp3 and Vp4 groups (OS p = 0.457, RFS p = 0.985). Patients who achieved a pathological complete response had significantly better RFS (p = 0.011). CONCLUSION Salvage surgery after combination therapy demonstrated favorable efficacy and safety. The novel surgical approach for PVTT can effectively achieve complete removal of PVTT and ensured long-term portal vein patency.
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Affiliation(s)
- Tianyu Jiao
- Medical School of Chinese PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China, 100853
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepetobiliary Surgery, PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General, Beijing, China
| | - Haowen Tang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China, 100853
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepetobiliary Surgery, PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General, Beijing, China
| | - Wenwen Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China, 100853
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepetobiliary Surgery, PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General, Beijing, China
| | - Bingyang Hu
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepetobiliary Surgery, PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General, Beijing, China
| | - Tao Wan
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepetobiliary Surgery, PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General, Beijing, China
| | - Yinbiao Cao
- Medical School of Chinese PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China, 100853
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepetobiliary Surgery, PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General, Beijing, China
| | - Ze Zhang
- Medical School of Chinese PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China, 100853
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepetobiliary Surgery, PLA, Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General, Beijing, China
| | - Yafei Wang
- Nankai University School of Medicine, Tianjin, China
| | - Junning Cao
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, China
| | - Mengqiu Cui
- Medical School of Chinese PLA, Beijing, China
- Department of Radiology, the, First Medical Centre , Chinese PLA General Hospital, Beijing, China
| | - Shichun Lu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China, 100853.
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China.
- Key Laboratory of Digital Hepetobiliary Surgery, PLA, Beijing, China.
- Nankai University School of Medicine, Tianjin, China.
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General, Beijing, China.
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Yang D, Du J, Nie W, Wang C, Ma Z. Combination treatment of transcatheter arterial chemoembolization, intensity-modulated radiotherapy, and sorafenib for hepatocellular carcinoma with macrovascular invasion. Medicine (Baltimore) 2023; 102:e35713. [PMID: 37960807 PMCID: PMC10637514 DOI: 10.1097/md.0000000000035713] [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: 07/10/2023] [Accepted: 09/28/2023] [Indexed: 11/15/2023] Open
Abstract
This study evaluated the therapeutic effects and toxic reactions of combining transcatheter arterial chemoembolization (TACE) and intensity-modulated radiotherapy (IMRT) with sorafenib for the treatment of advanced hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI). We retrospectively analyzed the clinical data of 82 HCC patients with MVI, among whom 35 were treated with TACE plus IMRT alone, and 47 were treated with the combined therapy of TACE, IMRT, and sorafenib. The progression-free survival (PFS), overall survival (OS), and adverse events were assessed. The baseline characteristics were comparable between the 2 groups (all P > .05). In the TACE plus IMRT plus sorafenib group, the median PFS was 17.2 months (95% confidence interval, 14.1-19.9), significantly longer than the 9.4 months (95% confidence interval, 6.8-11.2) observed in the TACE plus IMRT group (P < .001). Additionally, patients treated with the TACE plus IMRT plus sorafenib showed a longer median OS than those treated with TACE plus IMRT alone (24.1 vs 17.3 months; P < .001). The occurrence rates of grade 1 to 2 hand-foot syndrome, other skin reactions, diarrhea, and hair loss were higher in the TACE plus IMRT plus sorafenib group (all P < .05). There were no grade 4 or higher adverse events in either group. The combination of TACE plus IMRT with sorafenib provided substantial clinical benefits in the treatment of HCC patients with MVI, increasing the tumor response rate and prolonging both PFS and OS. This approach demonstrated a tolerable and manageable safety profile.
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Affiliation(s)
- Dan Yang
- Department of Gastroenterology, 3201 Hospital, Hanzhong, China
| | - Jiaojiao Du
- Department of Gastroenterology, 3201 Hospital, Hanzhong, China
| | - Weijie Nie
- Department of Gastroenterology, 3201 Hospital, Hanzhong, China
| | - Chaozhi Wang
- Department of Gastroenterology, 3201 Hospital, Hanzhong, China
| | - Zhufang Ma
- Department of Gastroenterology, 3201 Hospital, Hanzhong, China
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10
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Ye Y, Wang Y, Xu H, Yi F. Network meta-analysis of adjuvant treatments for patients with hepatocellular carcinoma after curative resection. BMC Gastroenterol 2023; 23:320. [PMID: 37730533 PMCID: PMC10510134 DOI: 10.1186/s12876-023-02955-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 09/10/2023] [Indexed: 09/22/2023] Open
Abstract
PURPOSE The prevention of recurrence for patients with hepatocellular carcinoma after curative resection is still a great challenge in clinical practice. There are numerous studies that trying to search for favorable strategies to decrease the recurrence and prolong life span for these patients, whereas no consensus is reached till now. Herein, we aim to compare the efficacy between different reported treatments by network meta-analysis(NMA). METHODS We searched Pubmed, Web of Science and Cochrane Library for abstracts and full-text articles published from database inception through February 2023. All of the random controlled trials(RCTs) were evaluated and collected as eligible studies. The primary outcome was the prevention of recurrence between different procedures. The second outcomes were one-year survival, three-year survival and five-year survival. RESULTS Thirty-two RCTs including 5783 patients were selected, and 12 treatments were classified. Most of the studies were high quality with low bias. Thirty-one studies including 5629 patients were recruited for recurrence analysis. The network meta-analysis showed benefits from transarterial chemoembolization(TACE) + portal vein chemotherapy(PVC)[OR, 2.84 (1.15,6.99)] and internal radiotherapy(IRT) [OR, 2.63 (1.41,4.91)] compared to non-adjuvant(NA) treatment when considering prevention of recurrence. Seventeen studies including 2047 patients were collected for one-year survival analysis. The network meta-analysis showed benefit from TACE[OR, 0.33 (0.14,0.75)] when considering one-year survival. Twenty-one studies including 2463 patients were collected for three-year survival analysis. The network meta-analysis showed TACE [OR, 0.51 (0.30,0.86)], IRT[OR, 0.41 (0.20,0.83)] and dendritic cell(DC) [OR, 0.09 (0.01,0.98)] were better than NA when considering three-year survival. Sixteen studies including 1915 patients were collected for five-year survival analysis. The network meta-analysis didn't show any benefit from different treatments when considering five-year survival. Other strategies including external radiotherapy(ERT), branched-chain amino acids(BCAA), hepatic artery infusion chemotherapy(HAIC), cytokine-induced killer(CIK), adoptive immunotherapy(AIT), Huaier, interferon(IFN), oral chemotherapy(OCT) and sorafenib(SOR) didn't show significant benefit regardless of prevention of recurrence or short-, long- time survival. CONCLUSION This NMA found that TACE + PVC and IRT were considered as the procedures to decrease HCC recurrence rate. TACE, IRT and DC were preferred when considering the extending of life span for post-operative patients with HCC. Large scale of RCTs are needed to verify it.
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Affiliation(s)
- Yanyan Ye
- Department of Ultrasound, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R. of China
| | - Ying Wang
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R. of China
- JiangXi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, 330006, P.R. of China
| | - Haoqian Xu
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R. of China
- JiangXi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, 330006, P.R. of China
| | - Fengming Yi
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R. of China.
- JiangXi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, 330006, P.R. of China.
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11
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Sun H, Ma B, Sun N, Bai H, Li X, Zhang C. Survival benefit of perioperative locoregional adjuvant treatment for hepatocellular carcinoma with portal vein tumor thrombosis: A systematic review and Bayesian network meta-analysis. Crit Rev Oncol Hematol 2023; 189:104083. [PMID: 37536447 DOI: 10.1016/j.critrevonc.2023.104083] [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: 05/24/2023] [Revised: 07/13/2023] [Accepted: 07/30/2023] [Indexed: 08/05/2023] Open
Abstract
BACKGROUND To identify the optimal strategy for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) by comparing the oncological prognosis of different perioperative locoregional adjuvant treatments. METHODS Electronic database were searched for relevant studies. Overall survival (OS) and recurrence-free survival (RFS) were pooled by pairwise and network meta-analysis. RESULTS Fourteen eligible trials with 1927 patients and covering four adjuvant treatments were included. All adjuvant therapies in combination with surgery were shown to be superior to surgery alone. Adjuvant therapy with radiotherapy had the lowest hazard ratio (HR) for both OS (HR: 0.38, 95% CrI: 0.25-0.57) and RFS (HR: 0.27, 95% CrI: 0.11-0.65) compared with other combination treatments, with estimated surface under the cumulative ranking of 93.2% and 82.7%, respectively. CONCLUSIONS Perioperative locoregional adjuvant therapy provides OS benefits and reduces the risk of recurrence for patients suffering from HCC with PVTT. Radiotherapy is likely to be the most effective adjuvant regimen.
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Affiliation(s)
- Hao Sun
- Department of Clinical Epidemiology and Evidence-Based Medicine, the First Hospital of China Medical University, Shenyang, China
| | - Bing Ma
- Department of Clinical Epidemiology and Evidence-Based Medicine, the First Hospital of China Medical University, Shenyang, China
| | - Ning Sun
- Department of Hepatobiliary Surgery, the First Hospital of China Medical University, Shenyang, China
| | - Han Bai
- Department of Hepatobiliary Surgery, the First Hospital of China Medical University, Shenyang, China
| | - Xuejian Li
- Department of Hepatobiliary Surgery, the First Hospital of China Medical University, Shenyang, China
| | - Chengshuo Zhang
- Department of Hepatobiliary Surgery, the First Hospital of China Medical University, Shenyang, China.
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12
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Sidhu MS, Ramandeep, Sood S, Aggarwal R, Singh K, Sood D. Role of rapid arc-image-guided radiotherapy in hepatocellular carcinoma with portal vein tumor thrombosis: A study from tertiary care center in Punjab, India. J Cancer Res Ther 2023; 19:639-643. [PMID: 37470587 DOI: 10.4103/jcrt.jcrt_365_21] [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: 11/04/2022]
Abstract
Background and Objectives Treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is very challenging with poor outcome. In this situation, radiotherapy has become an alternative treatment modality, more precisely due to advances in radiation techniques. The goal of our study is to do analysis of these patients treated with rapid arc image-guided technology (RA-IGRT) at our institution. Materials and Methods Thirteen patients were included in the study. As per intuition policy, patient set up, contouring, and treatment plans were generated. Radiological response assessment was done 1-month post-radiotherapy. Survival analysis curve along with Chi-square test for prognostic factors assessment was done using SPSS. Results With median dose of 45 Gy in 20 fractions, we were able to achieve 27.3% objective response rate with median survival of 5 months in eligible patients. Conclusions One-year overall survival up to 30% can be achieved in HCC with PVTT, especially in patients with objective response to radiotherapy with Japan Integrated Staging score 2, provided it is precisely hit by RA-IGRT.
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Affiliation(s)
| | - Ramandeep
- Department of Radiology, SPS Hospital, Ludhiana, Punjab, India
| | - Sandhya Sood
- Department of Radiation Oncology, DMCH Cancer Center, Ludhiana, Punjab, India
| | - Ritu Aggarwal
- Department of Radiation Oncology, DMCH Cancer Center, Ludhiana, Punjab, India
| | - Kulbir Singh
- Department of Medical Physics, DMCH Cancer Center, Ludhiana, Punjab, India
| | - Divyanshi Sood
- Department of Radiation Oncology, DMCH Cancer Center, Ludhiana, Punjab, India
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13
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Zhang M, Ding Q, Bian C, Su J, Xin Y, Jiang X. Progress on the molecular mechanism of portal vein tumor thrombosis formation in hepatocellular carcinoma. Exp Cell Res 2023; 426:113563. [PMID: 36944406 DOI: 10.1016/j.yexcr.2023.113563] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 03/01/2023] [Accepted: 03/18/2023] [Indexed: 03/22/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with poor prognosis and high mortality. Early-stage HCC has no obvious clinical symptoms, and most patients are already at an advanced stage when they are diagnosed. Portal vein tumor thrombus (PVTT) is the most common complication and a poor prognostic factor for HCC, which frequently leads to portal vein hypertension, ascites, gastrointestinal bleeding, and tumor metastasis. The formation of PVTT is related to the complex structure and hemodynamic changes of the portal vein and is closely related to changes at the cellular and molecular levels. The differentially-expressed genes (DEGs) between PVTT and primary tumor (PT) suggest that the two tissues may have different clonal origins. Epigenetic and proteomic analyses also suggest complex and diverse mechanisms for the formation of PVTT. In addition, the tumor microenvironment and energy metabolism pathways are interrelated in regulating the invasion and progression of PVTT. Aerobic glycolysis and the tumor immune microenvironment have been the focus of recent studies on PVTT. In this review, we summarize the mechanism of PVTT formation at the cellular and molecular levels to provide information to guide better prevention and treatment of PVTT in the clinic.
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Affiliation(s)
- Min Zhang
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, Changchun, 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, 130021, China.
| | - Qiuhui Ding
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, Changchun, 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, 130021, China.
| | - Chenbin Bian
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, Changchun, 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, 130021, China.
| | - Jing Su
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, Changchun, 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, 130021, China.
| | - Ying Xin
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China.
| | - Xin Jiang
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, Changchun, 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, 130021, China.
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14
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Zhou XH, Li JR, Zheng TH, Chen H, Cai C, Ye SL, Gao B, Xue TC. Portal vein tumor thrombosis in hepatocellular carcinoma: molecular mechanism and therapy. Clin Exp Metastasis 2023; 40:5-32. [PMID: 36318440 DOI: 10.1007/s10585-022-10188-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 10/04/2022] [Indexed: 11/05/2022]
Abstract
Portal vein tumor thrombosis (PVTT), a common complication of advanced hepatocellular carcinoma (HCC), remains the bottleneck of the treatments. Liver cancer cells potentially experienced multi-steps during PVTT process, including cancer cells leave from cancer nest, migrate in extracellular matrix, invade the vascular barrier, and colonize in the portal vein. Accumulated evidences have revealed numerous of molecular mechanisms including genetic and epigenetic regulation, cancer stem cells, immunosuppressive microenvironment, hypoxia, et al. contributed to the PVTT formation. In this review, we discuss state-of-the-art PVTT research on the potential molecular mechanisms and experimental models. In addition, we summarize PVTT-associated clinical trials and current treatments for PVTT and suppose perspectives exploring the molecular mechanisms and improving PVTT-related treatment for the future.
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Affiliation(s)
- Xing-Hao Zhou
- Liver Cancer Institute, Fudan University, Zhongshan Hospital, 136 Yi Xue Yuan Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China.,Department of Hepatic Oncology, Fudan University, Zhongshan Hospital, Shanghai, 200032, China.,National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China
| | - Jing-Ru Li
- Liver Cancer Institute, Fudan University, Zhongshan Hospital, 136 Yi Xue Yuan Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China.,Department of Hepatic Oncology, Fudan University, Zhongshan Hospital, Shanghai, 200032, China.,National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China
| | - Tang-Hui Zheng
- Liver Cancer Institute, Fudan University, Zhongshan Hospital, 136 Yi Xue Yuan Road, Shanghai, 200032, China.,Department of Hepatic Oncology, Xiamen Branch, Fudan University, Zhongshan Hospital, Xiamen, 361015, China
| | - Hong Chen
- Liver Cancer Institute, Fudan University, Zhongshan Hospital, 136 Yi Xue Yuan Road, Shanghai, 200032, China.,Department of Hepatic Oncology, Xiamen Branch, Fudan University, Zhongshan Hospital, Xiamen, 361015, China
| | - Chen Cai
- Liver Cancer Institute, Fudan University, Zhongshan Hospital, 136 Yi Xue Yuan Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China.,Department of Hepatic Oncology, Fudan University, Zhongshan Hospital, Shanghai, 200032, China.,National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China
| | - Sheng-Long Ye
- Liver Cancer Institute, Fudan University, Zhongshan Hospital, 136 Yi Xue Yuan Road, Shanghai, 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China.,Department of Hepatic Oncology, Fudan University, Zhongshan Hospital, Shanghai, 200032, China.,National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China
| | - Bo Gao
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai Medical College, Shanghai, 200032, China.
| | - Tong-Chun Xue
- Liver Cancer Institute, Fudan University, Zhongshan Hospital, 136 Yi Xue Yuan Road, Shanghai, 200032, China. .,Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China. .,Department of Hepatic Oncology, Fudan University, Zhongshan Hospital, Shanghai, 200032, China. .,National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China.
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15
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Deng J, Liao Z, Gao J. Efficacy of Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus: A Systematic Review and Meta-Analysis. Curr Oncol 2023; 30:1243-1254. [PMID: 36661745 PMCID: PMC9858211 DOI: 10.3390/curroncol30010096] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/06/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
Background: Transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) may enhance the efficacy of treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT); however, it remains unclear. We aim to evaluate the efficacy of TACE combined with TKIs. Methods: A thorough literature search was performed on major databases since their inception until October 2022. Based on the eligibility criteria, eight studies (2103 patients) were included. Results: Meta-analysis showed that TACE+sorafenib/apatinib had a better tumor response (objective response rate (ORR): RR = 4.85, 95% CI 2.68−8.75, disease control rate (DCR): RR = 3.23, 95% CI 1.88−5.56), and prolonged OS (HR = 0.50, 95%CI 0.42−0.60, p < 0.00001) than TACE alone. TACE+lenvatinib was stronger than TACE+sorafenib in ORR (60.7% vs. 38.9%) and TTP (HR = 0.61, 95% CI 0.43−0.86), whereas it was similar in DCR (96.4% vs. 96.3%) and OS (HR = 0.70 95% CI 0.46−1.05). Conclusions: TACE plus sorafenib or apatinib was superior to TACE alone for hepatocellular carcinoma with PVTT; no significant advantage was found between TACE+lenvatinib and TACE+sorafenib, although TACE+lenvatinib performed better in terms of ORR and TTP.
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Affiliation(s)
- Jia Deng
- Second Clinical College, Chongqing Medical University, Chongqing 400000, China
| | - Ziyue Liao
- Second Clinical College, Chongqing Medical University, Chongqing 400000, China
| | - Jian Gao
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400000, China
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16
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Lin X, Xiao M, Gu YJ, Zhu HK, Li MX, Zhuang L, Zheng SS, Li QY. The "No-touch" technique improves the survival of patients with advanced hepatocellular carcinomas treated by liver transplantation: A single-center prospective randomized controlled trial. Hepatobiliary Pancreat Dis Int 2022; 22:253-262. [PMID: 35568681 DOI: 10.1016/j.hbpd.2022.05.002] [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: 11/17/2021] [Accepted: 04/07/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver transplantation (LT) is the best treatment for patients with hepatocellular carcinoma (HCC). However, the surgical technique needs to be improved. The present study aimed to evaluate the "no-touch" technique in LT. METHODS From January 2018 to December 2019, we performed a prospective randomized controlled trial on HCC patients who underwent LT. The patients were randomized into two groups: a no-touch technique LT group (NT group, n = 38) and a conventional LT technique group (CT group, n = 46). Operative outcomes and survival in the two groups were analyzed. RESULTS The perioperative parameters were comparable between the two groups (P > 0.05). There was no significant difference between the two groups in disease-free survival (DFS) (P = 0.732) or overall survival (OS) (P = 0.891). Of 36 patients who were beyond the Hangzhou criteria for LT, the DFS of the patients in the NT group was significantly longer than that in the CT group (median 402 vs. 126 days, P = 0.025). In 31 patients who had portal vein tumor thrombosis (PVTT), DFS and OS in the NT group were significantly better than those in the CT group (median DFS 420 vs. 167 days, P = 0.022; 2-year OS rate 93.8% vs. 66.7%, P = 0.043). In 14 patients who had diffuse-type HCCs, DFS and OS were significantly better in the NT group than in the CT group (median DFS 141 vs. 56 days, P = 0.008; 2-year OS rate 75.0% vs. 33.3%, P = 0.034). Multivariate analysis showed that for patients with PVTT and diffuse-type HCCs, the no-touch technique was an independent favorable factor for OS (PVTT: HR = 0.018, 95% CI: 0.001-0.408, P = 0.012; diffuse-type HCCs: HR = 0.034, 95% CI: 0.002-0.634, P = 0.024). CONCLUSIONS The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique. The no-touch technique may provide a new and effective LT technique for advanced HCCs.
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Affiliation(s)
- Xin Lin
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Zhejiang University School of Medicine, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Min Xiao
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Yang-Jun Gu
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Heng-Kai Zhu
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Meng-Xia Li
- Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Li Zhuang
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China
| | - Shu-Sen Zheng
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Zhejiang University School of Medicine, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Qi-Yong Li
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China.
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17
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Tao ZW, Cheng BQ, Zhou T, Gao YJ. Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review. Hepatobiliary Pancreat Dis Int 2022; 21:134-144. [PMID: 34955380 DOI: 10.1016/j.hbpd.2021.12.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/05/2021] [Indexed: 02/09/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.
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Affiliation(s)
- Zi-Wen Tao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Bao-Quan Cheng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Tao Zhou
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yan-Jing Gao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
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18
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Shao Z, Liu X, Peng C, Wang L, Xu D. Combination of transcatheter arterial chemoembolization and portal vein embolization for patients with hepatocellular carcinoma: a review. World J Surg Oncol 2021; 19:293. [PMID: 34598689 PMCID: PMC8487116 DOI: 10.1186/s12957-021-02401-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 09/15/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Transcatheter arterial chemoembolization has been widely used in patients with hepatocellular carcinoma. However, double blood supply and the existence of portal vein tumor thrombus influence the efficacy of transcatheter arterial chemoembolization. MAIN BODY Theoretically, portal vein embolization combined with transcatheter arterial chemoembolization may bring a breakthrough in the therapeutic effect of hepatocellular carcinoma. The feasibility, efficacy, long-term survival benefits, and side effects of the combined treatment have been explored in previous studies. Chemotherapeutic agents may also be added in the portal vein embolization procedure to further improve the treatment response. CONCLUSION In this study, we review the existing data and studies on the combined treatment in patients with hepatocellular carcinoma and provide an overall view of the strategy.
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Affiliation(s)
- Zhiying Shao
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China
| | - Xin Liu
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China
| | - Chanjuan Peng
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China
| | - Liping Wang
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China
| | - Dong Xu
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China.
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Cao Y, Sun T, Guo X, Ouyang T, Kan X, Chen L, Liang B, Wang M, Zheng C. Sorafenib Versus Apatinib Both Combined Transarterial Chemoembolization for Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis: A Comparative Retrospective Study. Front Oncol 2021; 11:673378. [PMID: 34414104 PMCID: PMC8369468 DOI: 10.3389/fonc.2021.673378] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 07/19/2021] [Indexed: 01/26/2023] Open
Abstract
Objective To compare the efficacy and safety of transarterial chemoembolization (TACE) combining with sorafenib or apatinib for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Methods From June 2015 to March 2020, a total of 89 consecutive advanced HCC patients with PVTT who were treated with sorafenib-TACE (S-TACE) or apatinib-TACE (A-TACE) in our center were enrolled. The overall survival (OS), time to progression (TTP), tumor response, and adverse events in the two groups were compared. Results There were 32 and 41 patients included in the S-TACE group and A-TACE group, respectively. The median follow-up was 10.0 months (range, 3.0–36.0 months) in the whole study. The median OS (11.0 vs. 10.0 months, P = 0.419), median TTP (5.0 vs. 6.0 months, P = 0.073), and tumor response (P = 0.529) between the S-TACE group and the A-TACE group were not significantly different. The adverse events related to sorafenib or apatinib were tolerable. Conclusion S-TACE and A-TACE exhibited comparable prognosis for HCC patients with PVTT, which provide another effective and safe method of A-TACE for these patients except for conventional S-TACE.
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Affiliation(s)
- Yanyan Cao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xiaopeng Guo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Tao Ouyang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xuefeng Kan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Mingfu Wang
- Department of Radiology, The Third People's Hospital of Hubei Province, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
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20
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Hepatocellular carcinoma: metastatic pathways and extra-hepatic findings. Abdom Radiol (NY) 2021; 46:3698-3707. [PMID: 34091729 DOI: 10.1007/s00261-021-03151-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 01/10/2023]
Abstract
Although a small portion of patients with hepatocellular carcinoma (HCC) have radiologically evident extrahepatic disease at the initial presentation, a larger number of them develop metastatic disease later during the course of treatment or after definitive treatment. Furthermore, early metastatic disease could be overlooked by imaging due to small size and non-specificity of findings. Extrahepatic spread of HCC occurs via different pathways and is directly fueled by tumor biology and its molecular characteristics. Early and accurate detection of extrahepatic disease in patients with HCC has significant impact on management and selection of treatment options. Additionally, precise staging of disease will allow for better prediction of survival and outcome. Different pathways of regional and systemic spread of HCC with their proposed mechanisms and relevant underlying molecular derangement will be discussed in this article. Potential roles in management of patients with HCC will be discussed and reviewed in this article.
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21
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Li X, Ye Z, Lin S, Pang H. Predictive factors for survival following stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumour thrombosis and construction of a nomogram. BMC Cancer 2021; 21:701. [PMID: 34126955 PMCID: PMC8204556 DOI: 10.1186/s12885-021-08469-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 06/08/2021] [Indexed: 02/06/2023] Open
Abstract
Background We evaluated the treatment response and predictive factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT), who underwent stereotactic body radiotherapy (SBRT). Additionally, we developed and validated a personalised prediction model for patient survival. Methods Clinical information was retrospectively collected for 80 patients with HCC and PVTT, who were treated with SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) between December 2015 and June 2019. A multivariate Cox proportional hazard regression model was used to identify the independent predictive factors for survival. Clinical factors were subsequently presented in a nomogram. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the accuracy of the model and the net clinical benefit. Results All patients completed the planned radiotherapy treatment, and the median follow-up duration was 10 months (range, 1–35.3 months). The median survival duration was 11.5 months, with 3-, 6-, and 12-month survival rates of 92.5, 74.5, and 47.5%, respectively. The multivariable Cox regression model indicated that the following were significant independent predictors of OS: clinical T stage (p = 0.001, hazard ratio [HR] = 3.085, 95% confidence interval [CI]: 1.514–6.286), cirrhosis (p = 0.014, HR = 2.988, 95% CI: 1.246–7.168), age (p = 0.005, HR = 1.043, 95% CI: 1.013–1.075), alpha-fetoprotein level (p = 0.022, HR = 1.000, 95% CI: 1.000–1.000), and haemoglobin level (p = 0.008, HR = 0.979, 95% CI: 0.963–0.994). A nomogram based on five independent risk factors and DCA demonstrated a favourable predictive accuracy of patient survival (AUC = 0.74, 95% CI: 0.63–0.85) and the clinical usefulness of the model. Conclusions SBRT is an effective treatment for patients with HCC with PVTT. Notably, clinical T stage, presence of cirrhosis, age, alpha-fetoprotein levels, and haemoglobin levels are independent prognostic factors for survival. The presented nomogram can be used to predict the survival of patients with HCC and PVTT, who underwent SBRT.
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Affiliation(s)
- Xiaojie Li
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Zhimin Ye
- Department of Radiation Oncology, Cancer Hospital of The University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, China
| | - Sheng Lin
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
| | - Haowen Pang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
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22
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Chen KL, Gao J. Factors influencing the short-term and long-term survival of hepatocellular carcinoma patients with portal vein tumor thrombosis who underwent chemoembolization. World J Gastroenterol 2021; 27:1330-1340. [PMID: 33833486 PMCID: PMC8015298 DOI: 10.3748/wjg.v27.i13.1330] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 02/19/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The factors affecting the short-term and long-term prognosis of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) receiving transarterial chemoembolization (TACE) are still unclear.
AIM To clarify the predictors correlated with the short-term and long-term survival of HCC patients with PVTT who underwent TACE.
METHODS The medical records of 181 HCC patients with PVTT who underwent TACE at the Second Affiliated Hospital of Chongqing Medical University from January 2015 to July 2019 were retrospectively analyzed. We explored the short-term and long-term prognostic factors by comparing the preoperative indicators of patients who died and survived within 3 mo and 12 mo after TACE. Multivariate analyses were conducted using logistic regression. The area under the receiver operating characteristic curve (area under curve) was used to evaluate the predictive ability of the factors related to the short-term and long-term prognosis.
RESULTS The median survival time was 4.8 mo (range: 2.5-8.85 mo). The 3 mo, 6 mo, and 12 mo survival rates were 68.5%, 38.7%, and 15.5%, respectively. In multivariable analysis, total bilirubin, sex, and aspartate aminotransferase (AST) were closely linked to short-term survival. When AST ≥ 87 U/L and total bilirubin ≥ 16.15 µmol/L, the 3-mo survival rate after TACE was reduced significantly (P < 0.05). AST had the best predictive ability, followed by total bilirubin, while sex had the worst predictive ability for short-term survival area under curve: 0.763 (AST) vs 0.707 (total bilirubin) vs 0.554 (sex)]. The long-term survival outcome was significantly better in patients with a single lesion than in those with ≥ three lesions (P = 0.009). Patients with massive block HCC had a worse long-term survival than patients with nodular and diffuse HCC (P = 0.001).
CONCLUSION AST, total bilirubin, and sex are independent factors associated with short-term survival. The number of tumors and the gross pathological type of tumor are related to the long-term outcome.
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Affiliation(s)
- Ke-Li Chen
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Jian Gao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
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23
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Yuan G, Cheng X, Li Q, Zang M, Huang W, Fan W, Wu T, Ruan J, Dai W, Yu W, Chen M, Guo Y, Hu X, Chen J. Safety and Efficacy of Camrelizumab Combined with Apatinib for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Multicenter Retrospective Study. Onco Targets Ther 2020; 13:12683-12693. [PMID: 33328740 PMCID: PMC7734076 DOI: 10.2147/ott.s286169] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 11/19/2020] [Indexed: 12/24/2022] Open
Abstract
Introduction Previous trials demonstrated that anti-angiogenesis or anti-programmed death protein 1 (PD-1) monotherapy showed unsatisfied effect in advanced hepatocellular carcinoma (HCC). No study existed that focus on the effects of camrelizumab and apatinib ("C+A") combination therapy for HCC patients with the location and extent of portal vein tumor thrombus (PVTT) as the main variable being assessed. This study was to compare the efficacy and tolerability of "C+A" for HCC patients with PVTT. Methods We retrospectively analyzed patients with advanced HCC and PVTT who underwent "C+A" therapy in a multicenter retrospective cohort from Jan 2019 to July 2020. Outcomes of patients who underwent "C+A" were analyzed by using the Kaplan-Meier method according to types of PVTT: PVTT in the main portal vein (type A), PVTT in the first-order portal vein branch (type B), and PVTT in second- or lower-order portal vein branches (type C). Results Sixty-three patients were finally included and the mean duration of follow-up was 12.6 ± 4.5 months. The objective response rate (ORR) and disease control rate (DCR) for the whole cohort were 44.0% and 75.0%, respectively. The median overall survival (OS), progression-free survival (PFS) and time to progression (TTP) were 14.8 months, 11.8 months and not yet reached (NR), respectively. Patients with type B (OS, 15.9 months; PFS, 14.0 months; TTP, NR) or type C (OS, 16.0 months; PFS, 14.9 months; NR) PVTT appear to have better survival benefits compared with type A (OS, 5.8 months; PFS, 5.0 months; TTP, 7.0 months). Along with AFP, the absence of main PVTT was an independent predictive factor for survival at uni- and multivariate analysis. Conclusion Camrelizumab and apatinib yielded a promising outcome in patients with advanced HCC who developed a tumor thrombus in the first lower-order portal vein branches and was generally safe and had manageable side effects.
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Affiliation(s)
- Guosheng Yuan
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Xiao Cheng
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Qi Li
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.,Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Mengya Zang
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Wei Huang
- Department of Oncology, ShunDe Hospital, Southern Medical University, Foshan, People's Republic of China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Tao Wu
- Department of Infectious Disease, Hainan General Hospital, Haikou, People's Republic of China
| | - Jian Ruan
- Department of Medical Oncology, The First Affiliated Hospital, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Wencong Dai
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Wenxuan Yu
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Mian Chen
- Transplant Immunology Laboratory, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Headington, Oxford, UK
| | - Yabing Guo
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Xiaoyun Hu
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Jinzhang Chen
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.,Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
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24
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Ding X, Sun W, Chen J, Li W, Shen Y, Guo X, Teng Y, Liu X, Sun S, Wei J, Li W, Chen H, Liu B. Percutaneous Radiofrequency Ablation Combined With Transarterial Chemoembolization Plus Sorafenib for Large Hepatocellular Carcinoma Invading the Portal Venous System: A Prospective Randomized Study. Front Oncol 2020; 10:578633. [PMID: 33194699 PMCID: PMC7644860 DOI: 10.3389/fonc.2020.578633] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 09/28/2020] [Indexed: 01/27/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) portends a worse prognosis. The objective of this study was to compare the efficacy of percutaneous radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) plus sorafenib to that of the most commonly utilized regimen of TACE plus sorafenib in large HCCs with type I/II PVTT. Methods An open-label, single-center, prospective, randomized trial of participants with tumors ≥5 cm and type I/II PVTT was performed. Participants with previously untreated HCCs were divided into two groups: RFA + cTACE + sorafenib (study group, n = 40) and cTACE + sorafenib (control group, n = 40). The primary endpoint was the objective response rate (ORR), the secondary endpoints included the overall survival (OS); time to progression (TTP); and toxicity. Prognostic factors were analyzed using cox-regression analysis. Results 80 patients were enrolled into this study with integrated clinical data. Under a median follow-up of 506 days, the median age was 57.5 years (range: 28–80 years). The ORR of study group was higher than control group (70% vs 22.5%, p<0.001). Furthermore, the median OS of study group was superior to that of control group (468 days vs 219 days, HR: 0.44 [95% CI: 0.25–0.78], P = 0.005). Adverse events occurred with 100% probability in both groups (p>0.99), but no treatment-related deaths were recorded. Tumor encapsulation and attaining treatment response predict favorable OS in a multivariate Cox model. The rates of adverse events in both groups were 100% (p>0.99). There were no treatment-related deaths. Conclusions RFA combined with TACE plus sorafenib is a safe, well-tolerated three-modality treatment for large HCCs with types I/II PVTT, and it demonstrated better efficacy than TACE plus sorafenib alone.
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Affiliation(s)
- Xiaoyan Ding
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Sun
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jinglong Chen
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Li
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjun Shen
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaodi Guo
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ying Teng
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaomin Liu
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shasha Sun
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jianying Wei
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wendong Li
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hui Chen
- School of Biomedical Engineering, Capital Medical University, Beijing, China
| | - Bozhi Liu
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Hu J, Bao Q, Cao G, Zhu X, Yang R, Ji X, Xu L, Zheng K, Li W, Xing B, Wang X. Hepatic Arterial Infusion Chemotherapy Using Oxaliplatin Plus 5-Fluorouracil Versus Transarterial Chemoembolization/Embolization for the Treatment of Advanced Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis. Cardiovasc Intervent Radiol 2020; 43:996-1005. [PMID: 31974744 DOI: 10.1007/s00270-019-02406-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 12/31/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) to transarterial chemoembolization/embolization (TACE/TAE) for the treatment of advanced hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS Forty-six patients with advanced HCC with major PVTT who underwent HAIC or TACE/TAE between April 2013 and April 2017 were included. In the HAIC group (n = 22), oxaliplatin (35-40 mg/m2 for 2 h) and 5-fluorouracil (600-800 mg/m2 for 22 h) on days 1-3 every 4 weeks were administered for a maximum of six serial courses. In the TACE/TAE group (n = 24), an emulsion of epirubicin (40-60 mg) and lipiodol was administered followed by particles (cTACE), or particles alone embolization (TAE). Overall survival (OS), tumor response according to mRECIST, progression-free survival (PFS), and adverse events were investigated. RESULTS Median OS was 20.8 months in the HAIC group versus 4.0 months in the TACE/TAE group (P < 0.001; hazard ratio [HR], 0.17). The HAIC group showed higher tumor response rates than the TACE/TAE group (59.1% [13/22] vs. 22.7% [5/22]; P = 0.014) and a longer median PFS (9.6 vs. 1.5 months; P < 0.001; HR, 0.09). The Child-Pugh class (P = 0.007) and treatment method (P = 0.002) were independent risk factors of survival. The most frequent grade 3 or worse treatment-related adverse events were liver dysfunction (2 [9.1%] vs. 5 [20.8%]), hematological abnormalities (1 [4.5%] vs. 2 [8.3%]), and fever (1 [4.5%] vs. 4 [16.7%]). One treatment-related death due to acute liver failure occurred 3 days after TACE treatment. CONCLUSION HAIC may significantly improve OS and provide better tumor control with mild side effects and preserved liver function in patients with advanced HCC with major PVTT compared to TACE/TAE treatment.
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Affiliation(s)
- Jungang Hu
- Department of Interventional Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Quan Bao
- Department of Hepatic, Biliary and Pancreatic Surgery, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 100142, China
| | - Guang Cao
- Department of Interventional Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xu Zhu
- Department of Interventional Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Renjie Yang
- Department of Interventional Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xinqiang Ji
- Department of Medical Statistics, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, 100142, China
| | - Liang Xu
- Department of Interventional Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Kanglian Zheng
- Department of Interventional Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Weiliang Li
- Department of Interventional Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Baocai Xing
- Department of Hepatic, Biliary and Pancreatic Surgery, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 100142, China
| | - Xiaodong Wang
- Department of Interventional Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, 100142, China.
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26
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Yang Z, Luo FZ, Wang S, Lerut J, Zhuang L, Li QY, Xu X, Zheng SS. Alpha-fetoprotein and 18F-FDG standard uptake value predict tumor recurrence after liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis: Preliminary experience. Hepatobiliary Pancreat Dis Int 2020; 19:229-234. [PMID: 32303439 DOI: 10.1016/j.hbpd.2020.03.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 03/23/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Portal vein tumor thrombosis (PVTT) is regarded as a contraindication for liver transplantation (LT) in hepatocellular carcinoma (HCC). However, some of these patients may have a favorable prognosis after LT. In this study, we evaluated the biological behavior of HCC with PVTT using tumor biomarker (alpha-fetoprotein, AFP) and 18F-FDG positron emission tomography (tumor standard uptake value) to identify a subset of patients who may be suitable for LT. METHODS Seventy-five HCC-PVTT liver recipients transplanted during February 2016 and June 2018 were analyzed. Different pre-transplant prognostic factors were identified by univariate and multivariate analyses. PVTT status was identified following Vp classification (Vp1-Vp4). RESULTS Three-year recurrence-free survival and overall survival rates were 40% and 65.4% in Vp2-Vp3 PVTT patients, 21.4% and 30.6% in Vp4 PVTT patients (P < 0.05). Total tumor diameter >8 cm, pre-transplant AFP level >1000 ng/mL and intrahepatic tumor maximal standard uptake value (SUVmax-tumor >5) were independent risk factors for HCC recurrence and overall survival after LT in Vp2-3 PVTT patients. Low risk patients were defined as total tumor diameter ≤8 cm; or if total tumor diameter more than 8 cm, with both pre-transplant AFP level less than 1000 ng/mL and intrahepatic tumor SUVmax less than 5, simultaneously. Twenty-two Vp2-3 PVTT HCC patients (46.8%) were identified as low risk patients, and their 3-year recurrence-free and overall survival rates were 67.6% and 95.2%, respectively. CONCLUSIONS Patients with segmental or lobar PVTT and biologically favorable tumors defined by AFP and 18F-FDG SUVmax might be suitable for LT.
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Affiliation(s)
- Zhe Yang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China; Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; National Clinical Research Center of Infectious Diseases, Hangzhou, China
| | - Fang-Zhou Luo
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shuo Wang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Jan Lerut
- Starzl Unit of Abdominal Transplantation, University Hospitals Saint Luc, Université catholique Louvain, Brussels, Belgium
| | - Li Zhuang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Qi-Yong Li
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Xiao Xu
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; National Clinical Research Center of Infectious Diseases, Hangzhou, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China; Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; National Clinical Research Center of Infectious Diseases, Hangzhou, China.
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27
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Li S, Li L, Li B, Wang W. Safety and efficacy of endovascular implantation of a portal vein stent combined with iodine-125 seed-strips followed by transcatheter arterial chemoembolization with sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombosis. Br J Radiol 2020; 93:20190279. [PMID: 32464068 DOI: 10.1259/bjr.20190279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To assess the safety and efficacy of endovascular implantation of a portal vein stent combined with iodine-125 seed-strips followed by transcatheter arterial chemoembolization with sorafenib (PVS-125I-TACE-S) for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS Between January 2015 and July 2017, 18 patients with PVTT caused by HCC that were treated with PVS-125I-TACE-S were reviewed. The technical success, complications, changes in liver function from baseline values due to subsequent endovascular implantation of a portal vein stent combined with iodine-125 seed-strips (PVS-125I), time-to-tumor progression (TTP) and overall survival (OS) were observed. RESULTS The technical success rate was 100%. Adverse events (AEs) were managed successfully, with no occurrence of procedure-related deaths. Liver function test values after PVS-125I were not significantly different than baseline values (P＞0.05). The median TTP was 7.0 months (range: 4.2-9.9 months). In Vp3 PVTT, the TTP was 9.7 months (range: 8.8-10.5 months), and in Vp4 PVTT, the TTP was 4.2 months (range: 2.8-5.6 months). The median OS was 10.0 months (range: 7.0-13.1 months). In Vp3 PVTT, OS was 11.9 months (range: 9.2-14.5 months), and in Vp4 PVTT, OS was 7.2 months (range: 3.8-10.7 months). CONCLUSIONS PVS-125I-TACE-S is safe for patients with HCC with PVTT and may extend the TTP and survival of patients with Vp4 PVTT. ADVANCES IN KNOWLEDGE PVS implantation promptly restored flow in the obstructed portal vein, which can reduce the risk of hepatic failure and upper gastrointestinal bleeding. Implantation of iodine-125 seed-strips may directly expose the portal tumor thrombus to radiation and kill cancer cells. Their combined use with TACE-S has a strong scientific rationale.
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Affiliation(s)
- Shuangxi Li
- Interventional Department, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Lei Li
- Interventional Department, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Baohua Li
- Interventional Department, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Wenhui Wang
- Interventional Department, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
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Zhao S, Zhang X, Wang M, Tan K, Dou W, Fan Q, Li H, Du X, Liu L. Identifying optimal candidates for liver resection or transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:586. [PMID: 32566613 PMCID: PMC7290527 DOI: 10.21037/atm.2020.02.83] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Background Recommended as the first-line treatment for advanced unresectable hepatocellular carcinoma (HCC), sorafenib has been shown to prolong median overall survival (OS) for patients. However, advanced HCC sees high heterogeneity across patient groups. Recently, a growing number of studies have indicated surgical resection and transarterial chemoembolisation (TACE) to perform well in patients with portal vein tumor thrombosis (PVTT). The aim of this study was to compare the outcomes of liver resection and TACE and to identify prognostic factors related to OS for BCLC stage C patients with performance status (PS) 1 who have a single tumor but no vascular invasion or extrahepatic spread. Methods A total of 323 consecutive patients in BCLC stage C with PS 1 who had only one tumor and no vascular invasion or extrahepatic spread were enrolled in this retrospective study, regardless of tumor size. Survival analyses were performed using the Kaplan-Meier analysis, and statistical differences between the TACE and sorafenib groups were examined by the log-rank test. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS. Results Based on the Kaplan-Meier curves, patients treated with surgical resection showed a better OS than those who underwent TACE, with OS at 1, 3, and 5 years (85.7%, 48.8%, and 33.3% vs. 66.6%, 21.8%, and 13.4%, respectively; log-rank P<0.001). Univariate and multivariate analyses demonstrated that tumor size, albumin, bilirubin, Child-Pugh score, and treatment method were significant prognostic factors for OS. According to the subgroup analyses based on tumor size, there were significant differences in OS among overall subsets between patients who underwent hepatectomy and those who underwent TACE therapy. Conclusions Liver resection had a better prognostic performance than TACE and should be put forward as an alternative treatment modality to TACE for BCLC stage C patients with PS 1 who have a single tumor and no vascular invasion or extrahepatic spread.
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Affiliation(s)
- Shoujie Zhao
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Xiangnan Zhang
- Division of Scientific Research, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Mengmeng Wang
- Department of Drug and Equipment, Aeromedicine Identification and Training Centre of Air Force, Xi'an 710069, China
| | - Kai Tan
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Weijia Dou
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Qingling Fan
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Huichen Li
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China
| | - Xilin Du
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Lei Liu
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
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A case of complete remission of advanced hepatocellular carcinoma with type III portal vein tumor thrombosis treated using transarterial chemoembolization with microspheres and radiation therapy. Clin J Gastroenterol 2020; 13:847-854. [PMID: 32350739 DOI: 10.1007/s12328-020-01124-5] [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: 10/03/2019] [Accepted: 04/11/2020] [Indexed: 10/24/2022]
Abstract
Portal vein tumor thrombosis (PVTT) is an extremely locally advanced form of hepatocellular carcinoma. The natural median survival time of patients with hepatocellular carcinoma with PVTT is 2.7 to 4.0 months. A 63-year-old woman visited our clinic complaining of abdominal distention and appetite loss, which she had had for 3 weeks prior to admission. A contrast-enhanced computed tomography scan showed double hepatocellular carcinomas with Type III PVTT and massive ascites caused by arterio-portal shunts within the PVTT. The ascites could not be treated by concentrated ascites reinfusion therapy or diuretics. Transarterial embolization using microspheres followed by radiation therapy against PVTT and five courses of transarterial chemoembolization using microspheres and cisplatin led to the maintaining of complete remission of both ascites and tumors for over 12 months after treatment. Fluoroglucose accumulation of PVTT showed 11.2 as a maximum standard uptake value on positron emission tomography before treatment. No fluoroglucose accumulation within PVTT was observed for over 12 months following treatment. Transarterial chemoembolization using microspheres followed by radiation therapy against Type III PVTT may result in drastic anti-cancer effects and improvement of both serum albumin and intractable ascites after treatment of arterio-portal shunts within the PVTT causing portal hypertension.
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30
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Kumar A, Acharya SK, Singh SP, Arora A, Dhiman RK, Aggarwal R, Anand AC, Bhangui P, Chawla YK, Datta Gupta S, Dixit VK, Duseja A, Kalra N, Kar P, Kulkarni SS, Kumar R, Kumar M, Madhavan R, Mohan Prasad V, Mukund A, Nagral A, Panda D, Paul SB, Rao PN, Rela M, Sahu MK, Saraswat VA, Shah SR, Shalimar, Sharma P, Taneja S, Wadhawan M. 2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations. J Clin Exp Hepatol 2020; 10:43-80. [PMID: 32025166 PMCID: PMC6995891 DOI: 10.1016/j.jceh.2019.09.007] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/15/2019] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.
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Key Words
- AFP, alpha-fetoprotein
- AIH, autoimmune hepatitis
- ALT, alanine aminotransferase
- DAA, direct-acting antiviral
- DALY, disability-adjusted life-year
- DNA, deoxyribonucleic acid
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- Gd-BOPTA, gadolinium benzyloxypropionictetraacetate
- Gd-EOB-DTPA, gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid
- HBV, hepatitis B virus
- HBeAg, hepatitis B envelope antigen
- HCC, hepatocellular carcinoma
- HIV, human immunodeficiency virus
- IARC, International Agency for Research on Cancer
- IFN, interferon
- INASL, Indian National Association for Study of the Liver
- MiRNA, micro-RNA
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- PIVKA, protein induced by vitamin K absence
- RFA
- RNA, ribonucleic acid
- SVR, sustained virological response
- TACE
- TACE, trans-arterial chemoembolization
- TARE, transarterial radioembolization
- TNF, tumor necrosis factor
- WHO, World Health Organization
- liver cancer
- targeted therapy
- transplant
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Affiliation(s)
- Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
| | - Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Anil C. Anand
- Department of Gastroenterology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110 076, India
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Yogesh K. Chawla
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| | - Siddhartha Datta Gupta
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221 005, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Naveen Kalra
- Department of Radio Diagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Premashish Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
| | - Suyash S. Kulkarni
- Division of Interventional Radiology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, Maharashtra, 400 012, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver & Biliary Sciences, Sector D-1, Vasant Kunj, New Delhi, 110 070, India
| | - Ram Madhavan
- Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita University, Peeliyadu Road, Ponekkara, Edappally, Kochi, Kerala, 682 041, India
| | - V.G. Mohan Prasad
- Department of Gastroenterology, VGM Gastro Centre, 2100, Trichy Road, Rajalakshmi Mills Stop, Singanallur, Coimbatore, Tamil Nadu, 641 005, India
| | - Amar Mukund
- Department of Radiology, Institute of Liver & Biliary Sciences, Sector D-1, Vasant Kunj, New Delhi, 110 070, India
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Dipanjan Panda
- Department of Oncology, Institutes of Cancer, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110 076, India
| | - Shashi B. Paul
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Padaki N. Rao
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, No. 6-3-661, Punjagutta Road, Somajiguda, Hyderabad, Telangana, 500 082, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600 100, India
| | - Manoj K. Sahu
- Department of Medical Gastroenterology, IMS & SUM Hospital, K8 Kalinga Nagar, Shampur, Bhubaneswar, Odisha 751 003, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Samir R. Shah
- Department of Gastroenterology, Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Manav Wadhawan
- Liver & Digestive Diseases Institute, Institute of Liver & Digestive Diseases, BLK Super Specialty Hospital, Delhi, 110 005, India
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Apatinib Combined With Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombus: A Multicenter Retrospective Study. Clin Ther 2019; 41:1463-1476. [PMID: 31303279 DOI: 10.1016/j.clinthera.2019.04.036] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 04/21/2019] [Accepted: 04/24/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Studies focusing on the effects of combined transcatheter arterial chemoembolization (TACE) + the tyrosine kinase inhibitor apatinib in the treatment of patients with hepatocellular carcinoma (HCC), with the location and extent of portal vein tumor thrombus (PVTT) assessed as the main variable, are rare. This multicenter, retrospective, controlled study was performed to compare the efficacy and tolerability of TACE + apatinib and TACE alone in patients with HCC and PVTT. METHODS We retrospectively analyzed data from patients with nonresectable HCC and PVTT who underwent treatment with TACE + apatinib or TACE alone between January 2015 and January 2016. Outcomes in patients who underwent TACE + apatinib were compared with the outcomes of patients who underwent TACE alone, by using the Kaplan-Meier method, according to PVTT type: PVTT in the main portal vein (type A), PVTT in the first-order portal vein branch (type B), and PVTT in second- or lower-order portal vein branches (type C). FINDINGS One hundred eighty-eight patients were included in the analysis; 85 underwent treatment with TACE + apatinib and 103 underwent treatment with TACE. TACE + apatinib was associated with a significantly greater median survival compared with TACE alone in patients with PVTT type B (12.2 vs 7.5 months; P < 0.001) or type C (13.7 vs 7.2 months; P = 0.006). Along with treatment strategies and α-fetoprotein, the absence of main PVTT was an independent factor predictive of survival on uni- and multivariate analysis. Apatinib-related grade 3 adverse events occurred in 27 patients (31.8%). IMPLICATIONS TACE + apatinib can be of potential benefit to patients with advanced HCC with tumor thrombus in the first- and lower-order portal vein branches. Adverse events with apatinib need to be monitored during application, despite the manageable appearance.
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