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Kim SJ, Cummins KC, Tsung A. Immunotherapy as a Complement to Surgical Management of Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:1852. [PMID: 38791931 PMCID: PMC11120323 DOI: 10.3390/cancers16101852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 03/29/2024] [Accepted: 05/10/2024] [Indexed: 05/26/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver tumor in adults, and the fourth leading cause of cancer-related deaths worldwide. While surgical and ablative therapies remain the standard of care in early localized disease, late presentation with advanced stages of disease, impaired hepatic function, or local recurrence following surgical resection preclude operative management as the sole treatment modality in a subgroup of patients. As such, systemic therapies, namely immunotherapy, have become an integral part of the HCC treatment algorithm over the past decade. While agents, such as atezolizumab/bevacizumab, have well-established roles as first-line systemic therapy in intermediate- and advanced-stage HCC, the role of immunotherapy in disease amenable to surgical management continues to evolve. In this review, we will discuss the current evidence and aggregate impact of immunotherapy in the context of HCC amenable to surgical management, including its application in the neoadjuvant and adjuvant settings.
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Affiliation(s)
| | | | - Allan Tsung
- Department of Surgery, University of Virginia, Charlottesville, VA 22908, USA
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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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Wu Z, Cui L, Qian J, Luo L, Tu S, Cheng F, Yuan L, Zhang W, Lin W, Tang H, Li X, Li H, Zhang Y, Zhu J, Li Y, Xiong Y, Hu Z, Peng P, He Y, Liu L, He K, Shen W. Efficacy of adjuvant TACE on the prognosis of patients with HCC after hepatectomy: a multicenter propensity score matching from China. BMC Cancer 2023; 23:325. [PMID: 37029339 PMCID: PMC10080834 DOI: 10.1186/s12885-023-10802-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 04/01/2023] [Indexed: 04/09/2023] Open
Abstract
BACKGROUND The survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with hepatectomy for hepatocellular carcinoma (HCC) after hepatectomy remains controversial. We aimed to investigate the survival efficacy of adjuvant TACE after hepatectomy for HCC. METHODS 1491 patients with HCC who underwent hepatectomy between January 2018 and September 2021 at four medical centers in China were retrospectively analyzed, including 782 patients who received adjuvant TACE and 709 patients who did not receive adjuvant TACE. Propensity score matching (PSM) (1:1) was performed to minimize selection bias, which balanced the clinical characteristics of the two groups. RESULTS A total of 1254 patients were enrolled after PSM, including 627 patients who received adjuvant TACE and 627 patients who did not receive adjuvant TACE. Patients who received adjuvant TACE had higher disease-free survival (DFS, 1- ,2-, and 3-year: 78%-68%-62% vs. 69%-57%-50%, p < 0.001) and overall survival (OS, 1- ,2-, and 3-year: 96%-88%-80% vs. 90%-77%-66%, p < 0.001) than those who did not receive adjuvant TACE (Median DFS was 39 months). Among the different levels of risk factors affecting prognosis [AFP, Lymphocyte-to-monocyte ratio, Maximum tumor diameter, Number of tumors, Child-Pugh classification, Liver cirrhosis, Vascular invasion (imaging), Microvascular invasion, Satellite nodules, Differentiation, Chinese liver cancer stage II-IIIa], the majority of patients who received adjuvant TACE had higher DFS or OS than those who did not receive adjuvant TACE. More patients who received adjuvant TACE accepted subsequent antitumor therapy such as liver transplantation, re-hepatectomy and local ablation after tumor recurrence, while more patients who did not receive adjuvant TACE accepted subsequent antitumor therapy with TACE after tumor recurrence (All p < 0.05). CONCLUSIONS Adjuvant TACE may be a potential way to monitor early tumor recurrence and improve postoperative survival in patients with HCC.
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Affiliation(s)
- Zhao Wu
- Department of General Surgery, The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - Lifeng Cui
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The Second Clinical Medical College, The First Affiliated Hospital, Shenzhen People's Hospital, Jinan University, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen City, 518020, Guangdong Province, China
- Maoming People's Hospital, Mao Ming Shiy, China
| | - Junlin Qian
- Department of Hepatobiliary Surgery, Zhongshan People's Hospital (Zhongshan Hospital Affiliated to Sun Yat-sen University), No. 2, Sunwen East Road, Shiqi District, Zhongshan City, 528400, Guangdong Province, China
| | - Laihui Luo
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The First Clinical Medical College of Nanchang University, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - Shuju Tu
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The First Clinical Medical College of Nanchang University, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - Fei Cheng
- Department of General Surgery, The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - Lebin Yuan
- Department of General Surgery, The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - WenJian Zhang
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The Second Clinical Medical College, The First Affiliated Hospital, Shenzhen People's Hospital, Jinan University, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen City, 518020, Guangdong Province, China
| | - Wei Lin
- Department of Hepatobiliary Surgery, Zhongshan People's Hospital (Zhongshan Hospital Affiliated to Sun Yat-sen University), No. 2, Sunwen East Road, Shiqi District, Zhongshan City, 528400, Guangdong Province, China
| | - Hongtao Tang
- Department of Hepatobiliary Surgery, Zhongshan People's Hospital (Zhongshan Hospital Affiliated to Sun Yat-sen University), No. 2, Sunwen East Road, Shiqi District, Zhongshan City, 528400, Guangdong Province, China
| | - Xiaodong Li
- Department of General Surgery, The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - Hui Li
- School of Public Health, Nanchang University, Nanchang, China
| | - Yang Zhang
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The First Clinical Medical College of Nanchang University, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - Jisheng Zhu
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The First Clinical Medical College of Nanchang University, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - Yong Li
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The First Clinical Medical College of Nanchang University, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - Yuanpeng Xiong
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The First Clinical Medical College of Nanchang University, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang City, 330006, Jiangxi Province, China
| | - Zemin Hu
- Department of Hepatobiliary Surgery, Zhongshan People's Hospital (Zhongshan Hospital Affiliated to Sun Yat-sen University), No. 2, Sunwen East Road, Shiqi District, Zhongshan City, 528400, Guangdong Province, China
| | - Peng Peng
- Department of Hepatobiliary Surgery, Zhongshan People's Hospital (Zhongshan Hospital Affiliated to Sun Yat-sen University), No. 2, Sunwen East Road, Shiqi District, Zhongshan City, 528400, Guangdong Province, China
| | - Yongzhu He
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The First Clinical Medical College of Nanchang University, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang City, 330006, Jiangxi Province, China.
| | - Liping Liu
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, The Second Clinical Medical College, The First Affiliated Hospital, Shenzhen People's Hospital, Jinan University, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen City, 518020, Guangdong Province, China.
| | - Kun He
- Department of Hepatobiliary Surgery, Zhongshan People's Hospital (Zhongshan Hospital Affiliated to Sun Yat-sen University), No. 2, Sunwen East Road, Shiqi District, Zhongshan City, 528400, Guangdong Province, China.
| | - Wei Shen
- Department of General Surgery, The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang City, 330006, Jiangxi Province, China.
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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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Guo B, Chen Q, Liu Z, Chen X, Zhu P. Adjuvant therapy following curative treatments for hepatocellular carcinoma: current dilemmas and prospects. Front Oncol 2023; 13:1098958. [PMID: 37139151 PMCID: PMC10149944 DOI: 10.3389/fonc.2023.1098958] [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: 11/15/2022] [Accepted: 04/04/2023] [Indexed: 05/05/2023] Open
Abstract
Curative surgical treatments, mainly liver resection, are still one of the optimal options for patients with early-, mid-, and even progression-stage hepatocellular carcinoma (HCC). However, the recurrence rate within 5 years after surgery is as high as 70%, especially in patients with high risk factors for recurrence, most of whom experience early recurrence within 2 years. Effective adjuvant therapy may improve prognosis, previous studies found that adjuvant transarterial chemoembolization, antiviral, and traditional Chinese medicine et al. were helpful in preventing HCC recurrence. Nevertheless, due to controversial results or lack of high-level evidence, there is no standardized postoperative management protocol worldwide at present. Continued exploration of effective postoperative adjuvant treatments to improve surgical prognosis is necessary.
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Affiliation(s)
- Bin Guo
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qian Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hepatobiliary Surgery Department, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China
| | - Zhicheng Liu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Peng Zhu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- *Correspondence: Peng Zhu,
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Zeng ZM, Mo N, Zeng J, Ma FC, Jiang YF, Huang HS, Liao XW, Zhu GZ, Ma J, Peng T. Advances in postoperative adjuvant therapy for primary liver cancer. World J Gastrointest Oncol 2022; 14:1604-1621. [PMID: 36187393 PMCID: PMC9516643 DOI: 10.4251/wjgo.v14.i9.1604] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 05/13/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous, invasive, and conventional chemotherapy-insensitive tumor with unique biological characteristics. The main methods for the radical treatment of HCC are surgical resection or liver transplantation. However, recurrence rates are as high as 50% and 70% at 3 and 5 years after liver resection, respectively, and even in Milan-eligible recipients, the recurrence rate is approximately 20% at 5 years after liver transplantation. Therefore, reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer. This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization), adjuvant systemic therapy (e.g., molecular targeted agents and immunotherapy), and other adjuvant therapies (e.g., antiviral and herbal therapy). Finally, potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.
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Affiliation(s)
- Zhi-Ming Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ning Mo
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Fu-Chao Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yan-Feng Jiang
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hua-Sheng Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guang-Zhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Wang L, Qiu L, Ke Q, Ji H, Wu J. Systematic review of adjuvant external beam radiotherapy for hepatocellular carcinoma following radical hepatectomy. Radiother Oncol 2022; 175:101-111. [PMID: 35998838 DOI: 10.1016/j.radonc.2022.08.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 08/11/2022] [Accepted: 08/16/2022] [Indexed: 10/15/2022]
Abstract
BACKGROUND AND AIM Recurrence remains the main bottleneck hindering outcomes of hepatectomy for hepatocellular carcinoma (HCC). Owing to technological advances, external beam radiotherapy (EBRT) is being increasingly used in the management of HCC; however, there is no consensus on the role of adjuvant EBRT following hepatectomy. METHODS A systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. PubMed, MedLine, Embase, the Cochrane Library, Web of Knowledge were used to screen eligible studies (published as of May 1st, 2022) that evaluated the clinical safety and efficacy of EBRT for HCC receiving hepatectomy. The endpoints were disease-free survival (DFS), overall survival (OS), and adverse events (AEs). RESULTS A total of ten studies were eligible (three randomized controlled trials, one phase II trial, and six retrospective comparative studies). The pooled hazard ratio (HR) for median DFS and OS were both in favor of adjuvant EBRT compared with surgery alone (all P<0.05), and the advantage of adjuvant EBRT was also confirmed in subgroups stratified by different populations (narrow margin, P<0.05; microvascular invasion, P<0.05; portal vein tumor thrombus, P<0.05) and study designs (prospective studies, P<0.05; retrospective studies, P<0.05). Adjuvant EBRT was also found to be superior to adjuvant TACE (P<0.05). Pooled rates of overall AEs and severe AEs were 65.3% and 12.2%, but no fatal AEs were reported. CONCLUSION Adjuvant EBRT can be considered for HCC patients, especially those with a high risk of recurrence. Further studies are required for validation of these findings.
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Affiliation(s)
- Lei Wang
- College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, Fujian, China; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Lu Qiu
- Department of Radiation Oncology, Zhangzhou Affiliated Hospital of Fujian medical University, Fuzhou, Zhangzhou, China
| | - Qiao Ke
- College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, Fujian, China; Department of Hepatopancreatobiliary Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Hongbing Ji
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China.
| | - Junxin Wu
- College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, Fujian, China; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China.
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8
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Brown ZJ, Hewitt DB, Pawlik TM. Combination therapies plus transarterial chemoembolization in hepatocellular carcinoma: a snapshot of clinical trial progress. Expert Opin Investig Drugs 2021; 31:379-391. [PMID: 34788184 DOI: 10.1080/13543784.2022.2008355] [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] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Unfortunately, some hepatocellular carcinoma (HCC) patients do not qualify for curative-intent treatments such as surgical resection or transplantation. Hence, locoregional treatments such as transarterial chemoembolization (TACE) remain instrumental in the treatment of HCC. Systemic therapy has improved over the past decade with the introduction of combination atezolizumab and bevacizumab as the new standard of care for advanced disease. These new therapies are currently under investigation in combination with TACE. AREA COVERED Combination therapies with TACE including systemic therapies, locoregional therapies, and immunotherapies are reviewed. EXPERT OPINION There has been limited progress in the management of advanced and intermediate HCC. Recent advances in the management of advanced disease with systemic therapy could be beneficial in combination with TACE for the treatment of intermediate stage disease. Immune based therapies are potentially beneficial in combination with TACE because TACE may produce increased antigen release and immune recognition.
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Affiliation(s)
- Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - D Brock Hewitt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Esagian SM, Kakos CD, Giorgakis E, Burdine L, Barreto JC, Mavros MN. Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cancers (Basel) 2021; 13:2984. [PMID: 34203692 PMCID: PMC8232114 DOI: 10.3390/cancers13122984] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/07/2021] [Accepted: 06/09/2021] [Indexed: 02/07/2023] Open
Abstract
The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.
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Affiliation(s)
- Stepan M. Esagian
- Oncology Working Group, Society of Junior Doctors, 15123 Athens, Greece;
| | - Christos D. Kakos
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece;
| | - Emmanouil Giorgakis
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
| | - Lyle Burdine
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
| | - J. Camilo Barreto
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
| | - Michail N. Mavros
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece;
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
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10
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Zhang W, Zhang B, Chen XP. Adjuvant treatment strategy after curative resection for hepatocellular carcinoma. Front Med 2021; 15:155-169. [PMID: 33754281 DOI: 10.1007/s11684-021-0848-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 02/20/2021] [Indexed: 01/27/2023]
Abstract
Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.
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Affiliation(s)
- Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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11
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Wang W, Guo Y, Zhong J, Wang Q, Wang X, Wei H, Li J, Xiu P. The clinical significance of microvascular invasion in the surgical planning and postoperative sequential treatment in hepatocellular carcinoma. Sci Rep 2021; 11:2415. [PMID: 33510294 PMCID: PMC7843639 DOI: 10.1038/s41598-021-82058-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 01/12/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and most lethal malignant tumors in the world. Microvascular invasion (MVI) is a major risk factor for survival outcomes and intrahepatic metastasis after resection in patients with HCC. Relevant English literatures retrieved using PubMed on the research progress of MVI in patients with HCC were reviewed. For HCC patients, especially those with MVI, it is very important to develop a comprehensive and sequential treatment plan to support the long-term survival of patients. This manuscript reviewed and analyzed the risk factors for MVI; the preoperative prediction of MVI, which informs the selection of surgical strategies; and the current situation and future direction of comprehensive postoperative treatment strategies; to provide a basis for the comprehensive treatment of HCC patients with MVI. For HCC patients with MVI, the preoperative prediction of MVI may play a certain guiding role in planning procedures, and the comprehensive sequential postoperative pathological detection of HCC MVI may provide a basis for treatment decisions.
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Affiliation(s)
- Wentao Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Yaxun Guo
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jingtao Zhong
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Qi Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
| | - Xin Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Honglong Wei
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jie Li
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Peng Xiu
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China.
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China.
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12
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Liang L, Li C, Diao YK, Jia HD, Xing H, Pawlik TM, Lau WY, Shen F, Huang DS, Zhang CW, Yang T. Survival benefits from adjuvant transcatheter arterial chemoembolization in patients undergoing liver resection for hepatocellular carcinoma: a systematic review and meta-analysis. Therap Adv Gastroenterol 2020; 13:1756284820977693. [PMID: 33329759 PMCID: PMC7720303 DOI: 10.1177/1756284820977693] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 11/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although adjuvant transcatheter arterial chemoembolization (TACE) has been used to prevent recurrence after surgery in patients with hepatocellular carcinoma (HCC), the survival benefits from adjuvant TACE remain controversial. We sought to systematically evaluate the data on the effectiveness of adjuvant TACE for HCC, as well as identify patient populations that might benefit from adjuvant TACE. METHODS The PubMed, Embase, Medline and Cochrane library were systematically searched for studies published before July 2019 that compared adjuvant TACE versus surgery alone for HCC. The study endpoints were overall survival (OS) and disease-free survival (DFS). Patients with large HCC (⩾5 cm), multinodular HCC, microvascular invasion (MVI), or portal vein tumor thrombosis (PVTT) were analyzed in subgroup analyses. RESULTS Twenty-four studies with 6977 patients were included in the analytic cohort. The pooled analysis demonstrated that adjuvant TACE was associated with a better OS and DFS [hazard ratio (HR): 0.67 and 0.67, both p < 0.01]. In subgroup analyses, pooled results revealed that adjuvant TACE was associated with an improved OS and DFS in patients with multinodular HCC (HR: 0.79 and 0.31, both p < 0.01), MVI (HR: 0.62 and 0.67, both p < 0.01), or PVTT (HR: 0.49 and 0.58, both p < 0.01), but not among patients with large HCC (⩾5 cm). CONCLUSION Postoperative adjuvant TACE may be effective to improve OS and DFS in patients with multinodular HCC, or HCC with MVI or PVTT. Future randomized controlled trials are needed to better define the benefit of adjuvant TACE in subset patients with HCC.
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Affiliation(s)
- Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Yong-Kang Diao
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Hang-Dong Jia
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Timothy M. Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China Faculty of Medicine, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Dong-Sheng Huang
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Cheng-Wu Zhang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, Zhejiang, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
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13
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Hirokawa F, Komeda K, Taniguchi K, Asakuma M, Shimizu T, Inoue Y, Kagota S, Tomioka A, Yamamoto K, Uchiyama K. Is Postoperative Adjuvant Transcatheter Arterial Infusion Therapy Effective for Patients with Hepatocellular Carcinoma who Underwent Hepatectomy? A Prospective Randomized Controlled Trial. Ann Surg Oncol 2020; 27:4143-4152. [PMID: 32500344 DOI: 10.1245/s10434-020-08699-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND The effectiveness of adjuvant transcatheter arterial chemo- or/and chemoembolization therapy after curative hepatectomy of initial hepatocellular carcinoma (HCC) is controversial. This study aimed to evaluate whether hepatectomy combined with adjuvant transcatheter arterial infusion therapy (TAI) for initial HCC has better long-term survival outcomes than hepatectomy alone. METHODS From January 2012 to December 2014, a prospective randomized controlled trial of patients with initial HCC was conducted. Then, 114 initial HCC patients were recruited to undergo hepatectomy with adjuvant TAI (TAI group, n = 55) or hepatectomy alone (control group, n = 59) at our institution. The TAI therapy was performed twice, at 3 and 6 months after curative hepatectomy (UMIN 000011900). RESULTS The patients treated with TAI had no serious side effects, and operative outcomes did not differ between the two groups. No significant differences were found in the pattern of intrahepatic recurrence or time until recurrence between the two groups. Moreover, no significant differences were found in the relapse-free survival or overall survival. Low cholinesterase level (< 200) had been identified as a risk factor affecting relapse-free survival. Furthermore, compared with surgery alone, adjuvant TAI with hepatectomy improved the overall survival for lower-cholinesterase patients. CONCLUSIONS Adjuvant TAI is safe and feasible, but it cannot reduce the incidence of postoperative recurrence or prolong survival for patients who underwent curative hepatectomy for initial HCC.
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Affiliation(s)
- Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan.
| | - Koji Komeda
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Kohei Taniguchi
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan.,Translational Research Program, Osaka Medical College, Osaka, Japan
| | - Mitsuhiro Asakuma
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Tetsunosuke Shimizu
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Yoshihiro Inoue
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Shuji Kagota
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Atsushi Tomioka
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | | | - Kazuhisa Uchiyama
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
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14
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Chen W, Ma T, Zhang J, Zhang X, Chen W, Shen Y, Bai X, Liang T. A systematic review and meta-analysis of adjuvant transarterial chemoembolization after curative resection for patients with hepatocellular carcinoma. HPB (Oxford) 2020; 22:795-808. [PMID: 31980307 DOI: 10.1016/j.hpb.2019.12.013] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/15/2019] [Accepted: 12/20/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this study was to systematically evaluate and determine those patients with hepatocellular carcinoma (HCC) that would benefit from the administration of postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) and observational studies up to July 30, 2019. The outcome of Overall survival (OS) and disease-free survival (DFS) were extracted and converted to hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS A total of 40 studies (10 RCTs and 30 non-RCTs) involving 11,165 patients were included. Overall, PA-TACE was associated with an increased OS [HR, 0.71 (95% CI, 0.65-0.77); P < 0.001] and DFS [HR, 0.73 (95% CI, 0.66-0.80); P < 0.001]. Subgroup analysis in patients with microvascular invasion (MVI), tumor diameter >5 cm or multinodular tumors demonstrated that PA-TACE improved OS and DFS. In patients without MVI, PA-TACE showed no improvement in OS [HR, 1.14 (95% CI, 0.85-1.53); P = 0.370], and resulted in worse DFS than curative resection alone [HR, 1.20 (95% CI, 1.03-1.39); P = 0.002]. CONCLUSION This meta-analysis indicated that PA-TACE was beneficial in patients with HCC who were at high risk of postoperative recurrence including tumor diameter >5 cm, multinodular tumors and MVI-positive. In patients with tumor diameter ≤5 cm, single tumor or MVI-negative. PA-TACE does not appear to improve outcomes and may potentially promote postoperative recurrence in certain patients.
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Affiliation(s)
- Wen Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Tao Ma
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Jian Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Xiaozhen Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Yinan Shen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China.
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15
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Resection Plus Post-operative Adjuvant Transcatheter Arterial Chemoembolization (TACE) Compared with Resection Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Cardiovasc Intervent Radiol 2020; 43:572-586. [PMID: 31897617 DOI: 10.1007/s00270-019-02392-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 12/03/2019] [Indexed: 02/08/2023]
Abstract
PURPOSE Multiple studies have demonstrated adjuvant transcatheter arterial chemoembolization (aTACE) after resection improved outcomes compared to resection alone for patients with hepatocellular carcinoma (HCC). Unlike pre-operative TACE which targets a lesion, aTACE is administered in the proximal hepatic artery to destroy cancer cells within the remaining liver. This systematic review and meta-analysis aims to quantify this survival and disease-free survival (DFS) benefit. METHODS A search of five databases was performed from inception to 20 August 2019. RESULTS A total of 26 studies (six randomized controlled trials) involving 7817 patients were included. Patients treated with resection plus aTACE had significantly better 1-year survival (OR, 2.53 [95% CI, 1.70-3.76, p < 0.001) and 1-year DFS (OR, 1.91 [95% CI, 1.60-2.28, p < 0.001) compared to resection alone. The survival benefit remained significant for 2- to 5-year survival (OR 2.39, 1.83, 2.12, 1.87, respectively) and 2- to 4-year DFS (OR 1.85, 1.24, 1.67, respectively). Subgroup analysis showed significant survival benefit with aTACE in microvascular invasion (MVI)-positive HCC, portal venous tumour thrombus (PVTT) that does not involve the main trunk, PVTT-negative, satellite nodules, with and without resection margin < 1 cm. No mortalities were reported with aTACE. CONCLUSION Post-operative aTACE is safe and improves overall and disease-free survival, with the greatest benefit in MVI-positive patients. The current evidence weakly supports the use of adjuvant TACE for patients without PVTT, with PVTT that does not involve the main trunk, with and without a resection margin < 1 cm, and patients with satellite nodules. LEVEL OF EVIDENCE Level 1.
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16
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Lu SD, Li L, Liang XM, Chen W, Chen FL, Fan LL, Ahir BK, Zhang WG, Zhong JH. Updates and advancements in the management of hepatocellular carcinoma patients after hepatectomy. Expert Rev Gastroenterol Hepatol 2019; 13:1077-1088. [PMID: 31648568 DOI: 10.1080/17474124.2019.1684898] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023]
Abstract
Introduction: The 5-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection or local ablation is up to 70%. Adjuvant therapies to prevent HCC recurrence have been reported but are not currently recommended by EASL or AASLD guidelines. This review examined evidence from randomized controlled trials, meta-analyses and systematic reviews on the safety and efficacy of adjuvant therapies and chemotherapies in HCC patients after resection or local ablation.Areas covered: PubMed was searched through 15 June 2019. Available evidence was assessed based on the GRADE system.Expert commentary: Transarterial chemoembolization is the best adjuvant therapy for HCC patients at high risk of recurrence, antiviral therapy with nucleoside analogs is effective for preventing recurrence of HBV-related HCC, and interferon-α is effective for preventing recurrence of HCV-related HCC. Further studies are needed to clarify the efficacy of adjuvant immune checkpoint inhibitors. Adjuvant sorafenib appears to offer negligible clinical benefit and high risk of adverse effects.
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Affiliation(s)
- Shi-Dong Lu
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lin Li
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xin-Min Liang
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Wu Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Fu-Li Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Lang-Lin Fan
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Bhavesh K Ahir
- Section of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Wan-Guang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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17
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Chen ZH, Zhang XP, Zhou TF, Wang K, Wang H, Chai ZT, Shi J, Guo WX, Cheng SQ. Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis. Eur J Surg Oncol 2019; 45:2188-2196. [PMID: 31256949 DOI: 10.1016/j.ejso.2019.06.031] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 04/28/2019] [Accepted: 06/24/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The benefits of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remain controversial. We compared the efficacy and safety of adjuvant TACE and hepatic resection (HR) alone for HCC patients with MVI. METHODS The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare adjuvant TACE and HR alone for the treatment of HCC with MVI from inception to January 1, 2019. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors. RESULTS 12 trials involving 2190 patients were evaluated. A meta-analysis of 11 studies suggested that the 1-, 3-, and 5-year overall survival (OS) rates (OR = 0.33, P < 0.001; OR = 0.49, P < 0.001; and OR = 0.59, P < 0.01; respectively), favored adjuvant TACE over HR alone. 11 studies were included in the meta-analysis of DFS, and adjuvant TACE showed better 1-, 3-, and 5-DFS (OR = 0.45, P < 0.001; OR = 0.50, P < 0.001; and OR = 0.58, P < 0.001; respectively) compared to HR alone. Subgroup analysis demonstrated that adjuvant TACE could benefit HCC patients with MVI with tumor diameter >5 cm or multinodular tumors. CONCLUSION Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI. However, these results need to be validated through further high-quality clinical studies. LAY SUMMARY The benefits of adjuvant TACE in HCC patients with microvascular invasion remain controversial. Twelve studies involving 2190 patients were include in our meta-analysis. Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI.
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Affiliation(s)
- Zhen-Hua Chen
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | | | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Hang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zong-Tao Chai
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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18
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Zhang YF, Shang H, Zeng XL, Ji H, Li YM, Lu HW. Postoperative adjuvant chemo (embolization) therapy for hepatocellular carcinoma with portal vein tumor thrombosis. Onco Targets Ther 2018; 11:5407-5417. [PMID: 30214246 PMCID: PMC6128276 DOI: 10.2147/ott.s171612] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Background The present meta-analysis was aimed to evaluate the effects of postoperative adjuvant chemotherapy/transarterial chemoembolization (TACE) on the survival/disease-free survival (DFS) rate in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Methods The relevant trials were collected using a database search of MEDLINE, Embase, Cochrane Library, Web of Science, ScienceDirect, the China Journal Full-text Database, and the National Institute of Health Clinical Trials Database. The 1-, 3-, and 5-year survival/DFS rates were considered to be the primary end points. A sensitivity analysis was conducted by reanalyzing the data using different statistical approaches. Results Eight studies met the inclusion criteria. When compared with surgery alone, the pooled OR showed that the postoperative adjuvant therapy significantly increased the 1-, 3-, and 5-year survival rates for HCC patients with PVTT (the pooled OR and 95% CI of the 1-, 3-, and 5-year survival rates, respectively, were as follows: 2.72, 1.98-3.74; 1.62, 1.13-2.33; 1.99, 1.20-3.29). In addition, when compared with surgery alone, subgroup analysis showed that the postoperative chemotherapy improved the 1-, 3-, and 5-year survival rates of HCC patients with PVTT. Conclusion Compared with surgery alone, postoperative adjuvant chemotherapy can improve the 1-, 3- and 5-year survival rates of HCC patients with PVTT. However, postoperative TACE can only increase the 1-year survival rate. However, due to the limitations of this meta-analysis, additional relevant trials are required to confirm these findings.
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Affiliation(s)
- Ya-Fei Zhang
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Hao Shang
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Xian-Ling Zeng
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Hong Ji
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Yi-Ming Li
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Hong-Wei Lu
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
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Efficacy of Transarterial Chemoembolisation with or without Antiviral Therapy for Patients with Hepatocellular Carcinoma after Radical Hepatectomy. Gastroenterol Res Pract 2018; 2018:6414759. [PMID: 29805444 PMCID: PMC5902052 DOI: 10.1155/2018/6414759] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 01/04/2018] [Accepted: 01/09/2018] [Indexed: 02/06/2023] Open
Abstract
Objective This study aimed at assessing the effects of transcatheter arterial chemoembolisation (TACE) and antiviral therapy on improving the prognosis of patients with hepatocellular carcinoma (HCC) after radical hepatectomy. Methods This study reviewed the data of 120 patients with HCC who received either radical hepatectomy alone (control group), radical hepatectomy with postoperative TACE (TACE group) or radical hepatectomy with combined postoperative TACE, and antiviral therapy (combined group) from January 2000 to May 2015. To reduce the impact of the possible biases on the conclusion of this study to the minimum, the cases with similar demographic and clinicopathological characteristics were collected and 40 cases were assigned into each group. Recurrence, disease-free survival (DFS), and overall survival (OS) rates were compared. Results Median follow-up period was 54.26 ± 22.65 months with a range of 17–110 months. Recurrence after radical surgery was observed for 39 (97.5%) patients in the TACE group, 32 (80%) in the combined group, and 40 (100%) in the control group with median recurrence duration of 33, 43, and 16.5 months, respectively. Postoperative TACE with or without antiviral therapy significantly prolonged the DFS rate compared with radical hepatectomy alone (P = 0.000). TACE combined with antiviral therapy significantly extended the DFS rate compared with TACE alone (P = 0.008). Postoperative TACE with or without antiviral therapy also significantly prolonged the OS rate compared with radical hepatectomy alone (P = 0.000). In addition, antiviral therapy combined with TACE significantly extended the 5-year OS rate of patients compared with individual TACE and radical hepatectomy (67.5% versus 55% and 2.5%; P = 0.032). Conclusion TACE is an appropriate therapy for HCC patients after radical hepatectomy. When combined with antiviral therapy, this treatment may further prolong the recurrence time and thus lead to high DFS and OS rates.
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Adjuvant I-131 Lipiodol After Resection or Radiofrequency Ablation for Hepatocellular Carcinoma. World J Surg 2017; 40:1941-50. [PMID: 27098539 DOI: 10.1007/s00268-016-3502-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND OBJECTIVES High rates of recurrence have been observed after curative treatment for hepatocellular carcinoma (HCC). The main aim of this study was to establish the influence of adjuvant transarterial radioembolization-based I-131 lipiodol on survival and recurrence. METHODS Between 2004 and 2010, 38 patients were treated with adjuvant I-131 lipiodol therapy, at a dosage of 2220 MBq, within 4 months after surgery. This treated cohort was compared to a control cohort consisting of 42 consecutive patients operated prior to the time the I-131 lipiodol treatment became available. RESULTS Recurrence-free survival in the control and in the I-131 lipiodol cohort was 12.6 and 18.7 months, respectively (HR = 1.871, p = 0.025). At 2 and 5 years, the cumulative incidence of a first recurrence or death was, respectively, 50 % and 61 % in the treated cohort versus 69 % and 74 % in the control cohort. Median overall survival was 55 and 29 months, respectively (p = 0.051). Among patients with a recurrence at 2 years, more patients had already experienced such recurrence at 1 year in the control cohort (70 % vs 33 %, p = 0.014). CONCLUSIONS Adjuvant I-131 lipiodol improves disease-free survival in patients with HCC.
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Liao M, Zhu Z, Wang H, Huang J. Adjuvant transarterial chemoembolization for patients after curative resection of hepatocellular carcinoma: a meta-analysis. Scand J Gastroenterol 2017; 52:624-634. [PMID: 28276833 DOI: 10.1080/00365521.2017.1292365] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To evaluate the efficacy and safety of adjuvant transarterial chemoembolization (TACE) after curative hepatectomy in improving the survival of patients with primary hepatocellular carcinoma (HCC). METHODS MEDLINE, Embase and the Cochrane Library were searched for randomized or nonrandomized studies comparing postoperative adjuvant TACE with curative resection alone. Meta-analysis was performed after converting time-event data into a hazard ratio (HR), using an inverse diversity model. RESULTS Eight randomized controlled trials (RCTs) and 12 retrospective studies matched the selection criteria, thereby including 3191 patients (779 in RCT, 2412 in observational studies) for the meta-analysis. The meta-analysis showed that receiving adjuvant TACE was associated with improved overall survival (OS, ln[HR] = 0.70, 95%CI: 0.63-0.78, p < .001) and recurrence-free survival (RFS, ln[HR] = 0.69, 95%CI: 0.63-0.76, p < .001) after curative hepatectomies. The results of observational studies were consistent with those of RCTs. Furthermore, meta-regression was utilized to detect study-level factors associated with treatment outcome. It revealed that overall survival was similar among patients treated with various combinations of chemotherapeutic drugs. Subgroup analyses demonstrated that repeated TACE interventions do not provide a higher survival benefit compared with a single course, and patients with a single tumor or tumor size ≥5cm might stand to benefit the most from adjuvant TACE therapy. CONCLUSIONS This meta-analysis demonstrated that postoperative adjuvant TACE could achieve higher OS and RFS than surgical resection alone. However, these results need to be validated through further high-quality clinical studies.
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Affiliation(s)
- Mingheng Liao
- a Department of Liver Surgery , Liver Transplantation Division, West China Hospital, Sichuan University , Chengdu , China
| | - Zexin Zhu
- a Department of Liver Surgery , Liver Transplantation Division, West China Hospital, Sichuan University , Chengdu , China
| | - Haichuan Wang
- a Department of Liver Surgery , Liver Transplantation Division, West China Hospital, Sichuan University , Chengdu , China
| | - Jiwei Huang
- a Department of Liver Surgery , Liver Transplantation Division, West China Hospital, Sichuan University , Chengdu , China
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Jiang J, Hu H, Liu R, Wang JH, Long XR, Fan J, Yan ZP. Nomogram for individualized prediction of recurrence after postoperative adjuvant TACE for hepatitis B virus-related hepatocellular carcinoma. Medicine (Baltimore) 2017; 96:e7390. [PMID: 28796032 PMCID: PMC5556198 DOI: 10.1097/md.0000000000007390] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
This study sought to develop an effective and reliable nomogram for predictions of recurrence for postoperative adjuvant transarterial chemoembolization (PA-TACE) in patients with hepatitis B virus-related (HBV) hepatocellular carcinoma (HCC).The nomogram was established based on data obtained from a retrospective study on 235 consecutive patients with HBV HCC who received PA-TACE as an initial therapy from 2006 to 2010 in our center. Eighty-four patients who were collected at another institution between 01/2008 and 12/2010 served as an external validation set. Recurrence-free survival (RFS) was collected. The nomogram for tumor recurrence was developed based on the data obtained before the PA-TACE procedure. Predictive accuracy and discriminative ability of the nomogram were assessed by concordance index (C-index), calibration curves, and validation set.The 1, 2, 3-year RFS rates were 55.5%, 27.0%, and 14.1%, respectively, in the patients from the derivation set and 60.7%, 33.2%, and 23.8% in those from the validation set. Four risk factors (HBV-DNA level, vascular invasion, change of Child-Pugh score, and tumor diameter) in the multivariate analysis were significantly associated with RFS. The statistical nomogram incorporated these 4 factors achieved good calibration and discriminatory abilities with the c-index of 0.74 (95% CI 0.66-0.82). The findings were supported by the independent external validation set (c-index, 0.70; 95% CI 0.58-0.83). The area under the receiver operating characteristic curve in our model was greater than those of conventional staging systems in the validation patients (corresponding c-indices, 0.56-0.64).The novel nomogram may achieve an optimal prediction for recurrence outcome in HBV-related HCC with PA-TACE.
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Affiliation(s)
- Jiang Jiang
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
| | - Hao Hu
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
| | - Rong Liu
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
| | - Jian Hua Wang
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
| | | | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhi Ping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
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Sun JJ, Wang K, Zhang CZ, Guo WX, Shi J, Cong WM, Wu MC, Lau WY, Cheng SQ. Postoperative Adjuvant Transcatheter Arterial Chemoembolization After R0 Hepatectomy Improves Outcomes of Patients Who have Hepatocellular Carcinoma with Microvascular Invasion. Ann Surg Oncol 2015; 23:1344-51. [PMID: 26714945 DOI: 10.1245/s10434-015-5008-z] [Citation(s) in RCA: 127] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Microvascular invasion (MiVI) is a major risk factor of survival outcomes after curative resection for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the impact of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) on HCC patients with MiVI. METHODS From January 2004 to June 2013, HCC patients with histologically confirmed MiVI and well-tolerated liver function who underwent PA-TACE after R0 hepatectomy (RH) or RH alone were studied retrospectively. In the PA-TACE group, PA-TACE was given 4 weeks after RH. Uni- and multivariate analyses were used to identify the prognostic significance of PA-TACE. RESULTS Of the 322 HCC patients with MiVI included in the analysis, 185 entered into the RH group and 137 entered into the PA-TACE group. The baseline characteristics of the two groups were similar except for alanine aminotransferase (ALT) level (p = 0.037). The 1-, 2-, 3-, and 5-year recurrence-free survival (RFS) rates were respectively 69.3, 55.5, 46.7, and 35.0 % for the PA-TACE group and 47.0, 36.2, 34.1, and 30.3 % for the RH group (log-rank, χ(2) = 6.309; p = 0.012). The 1-, 2-, 3-, and 5-year overall survival (OS) rates were respectively 94.2, 78.8, 71.5, and 54.0 % for the PA-TACE group and 78.9, 62.2, 54.1, and 43.2 % for the RH group (log-rank, χ(2) = 7.537; p = 0.006). Multivariate Cox proportional hazards regression analysis showed PA-TACE to be an independent risk factor of postoperative RFS and OS. CONCLUSIONS This study showed that PA-TACE may be beneficial for HCC patients with MiVI.
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Affiliation(s)
- Jing Jian Sun
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Kang Wang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Cun Zhen Zhang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Wei Xing Guo
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Jie Shi
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Wen Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Meng Chao Wu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Wan Yee Lau
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.,Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Shu Qun Cheng
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.
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Qi X, Liu L, Wang D, Li H, Su C, Guo X. Hepatic resection alone versus in combination with pre- and post-operative transarterial chemoembolization for the treatment of hepatocellular carcinoma: A systematic review and meta-analysis. Oncotarget 2015; 6:36838-36859. [PMID: 26451613 PMCID: PMC4742214 DOI: 10.18632/oncotarget.5426] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Accepted: 09/22/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIMS The prognosis of hepatocellular carcinoma (HCC) treated with hepatic resection may be improved by the adjunctive use of transarterial chemoembolization (TACE). This study aimed to systematically compare the outcomes between hepatic resection with and without TACE groups. METHODS All relevant randomized controlled trials (RCTs) and non-RCTs were searched by the PubMed, EMBASE, and Cochrane Library databases. Overall survival (OS) and disease-free survival (DFS) were two major outcomes. Meta-analyses were performed according to the timing of TACE (pre- or post-operative TACE). Subgroup analyses were also performed. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated. RESULTS Overall, 55 papers were included (14 RCTs and 41 non-RCTs). Overall meta-analyses demonstrated that OS and DFS were statistically similar between hepatic resection with and without pre-operative TACE groups (HR = 1.01, 95%CI = 0.87-1.19, P = 0.87; HR = 0.91, 95%CI = 0.82-1.01, P = 0.07). Subgroup analyses of RCTs or non-RCTs showed that OS and DFS remained statistically similar between hepatic resection with and without pre-operative TACE groups. Subgroup analysis of incomplete or no tumor necrosis showed that OS was worse in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group. By contrast, subgroup analysis of complete tumor necrosis showed that DFS was better in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group.Overall meta-analyses demonstrated that OS and DFS were better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group (HR = 0.85, 95%CI = 0.72-1.00, P = 0.06; HR = 0.83, 95%CI = 0.73-0.94, P = 0.004). Subgroup analyses of RCTs, vascular invasion, or large HCC showed that OS and DFS remained better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group. By contrast, subgroup analyses of non-RCTs, no vascular invasion, or small HCC showed that OS and DFS were statistically similar between the two groups. CONCLUSIONS Post-operative TACE, rather than pre-operative TACE, may be considered as an adjunctive treatment option for HCC treated with hepatic resection.
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Affiliation(s)
- Xingshun Qi
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
| | - Lei Liu
- Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Diya Wang
- Department of Occupational and Environmental Health Sciences and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
| | - Chunping Su
- Library of Fourth Military Medical University, Xi'an, China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
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RETRACTED ARTICLE: Clinical value of circulating tumor cells for the prognosis of postoperative transarterial chemoembolization therapy. Med Oncol 2014; 31:175. [DOI: 10.1007/s12032-014-0175-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 08/09/2014] [Indexed: 12/12/2022]
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Cheng X, Sun P, Hu QG, Song ZF, Xiong J, Zheng QC. Transarterial (chemo)embolization for curative resection of hepatocellular carcinoma: a systematic review and meta-analyses. J Cancer Res Clin Oncol 2014; 140:1159-70. [PMID: 24752339 DOI: 10.1007/s00432-014-1677-4] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Accepted: 04/09/2014] [Indexed: 02/06/2023]
Abstract
PURPOSE To assess the beneficial and harmful effects of transarterial embolization (TAE) or transarterial chemoembolization (TACE) for curative resection of hepatocellular carcinoma (HCC). METHODS The authors conducted an extensive search of studies on this strategy. All randomized controlled trials comparing TACE or TAE plus operation versus operation only were considered for inclusion, regardless of blinding, language, or publication status. Results were performed with disease-free survival (DFS) and overall survival (OS) as the primary endpoint. Tumor response and adverse events were secondary endpoints. RESULTS A total of 10 studies involving 909 HCC participants finally fulfilled the predefined inclusion criteria. Four trials assessed preoperative TACE versus control and six trials assessed postoperative TACE versus control. There were significant improvements for DFS [HR 0.62 (95 % CI 0.49-0.79)] and OS [HR 0.60 (0.46-0.79)] in the postoperative TACE compared with the control when the mean tumor size was bigger than 5 cm. However, preoperative TACE did not improve DFS [HR 0.92 (0.71-1.20)] and OS [HR 1.07 (0.78-1.46)] for curative resection of HCC. Substantial differences in criteria for assessing tumor response did not allow quantitative analyses. Fever (26.7-85.9 %), abdominal pain (19.3-71.2 %), and nausea/vomiting (27.4-66.3 %) were common adverse events. Relatively rare but more serious complications were also reported. CONCLUSIONS Postoperative TACE offers potential benefits for curative resection of HCC when the mean tumor size is bigger than 5 cm.
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Affiliation(s)
- Xiang Cheng
- Hepatobiliary Surgery Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
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Abstract
Hepatocellular carcinoma (HCC) is associated with poor prognosis and often recurs even after curative hepatic resection (HR) or radiofrequency ablation (RFA). In fact, recurrence is the most frequent cause of postoperative death in patients with HCC; it can arise through intrahepatic metastasis by the primary tumor or through the emergence of de novo tumors. Even though studies have examined numerous adjuvant therapies and chemotherapies for their ability to prevent recurrence, no consensus recommendations exist about their clinical application. To gain a comprehensive picture of clinical options, we identified 39 randomized controlled trials, involving 4113 participants, which explore the efficacy of adjuvant or chemotherapies to prevent HCC recurrence after potentially curative HR or RFA. The available evidence suggests a significant improvement in recurrence-free survival and overall survival when transarterial chemoembolization is used for patients who are at high risk for recurrence, lamivudine for patients with hepatitis B virus (HBV)-related HCC (>500 copies of HBV DNA/ml), and interferon-α for patients with hepatitis C virus (HCV)-infected HCC. In contrast, available evidence does not definitively establish clinical benefits of interferon-β for patients with HCV-related HCC, interferon-α for patients with HBV-related HCC, or any of the following therapies for patients with HCC: iodine-125 brachytherapy, autologous tumor vaccination, adoptive immunotherapy, or therapy involving acyclic retinoid, vitamin K2 analog, iodine-131-labeled lipiodol, sorafenib, heparanase inhibitor PI-88, or capecitabine. Though the findings of our review should be interpreted with caution because of clinical heterogeneity and small sample size in the included trials, they highlight gaps in the evidence base, and therefore, may guide future research.
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Affiliation(s)
- Jian-Hong Zhong
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University , Nanning 530021 , PR China
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Zhang Q, Bai XL, Chen W, Ma T, Liu H, Zhang Y, Hu XJ, Liang TB. Postoperative adjuvant transarterial (chemo)embolisation after liver resection for hepatocellular carcinoma. Cochrane Database Syst Rev 2013. [DOI: 10.1002/14651858.cd010897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/09/2025]
Affiliation(s)
- Qi Zhang
- the Second Affiliated Hospital, School of Medicine, Zhejiang University; Department of Hepatobiliary and Pancreatic Surgery; 88 Jiefang Road Hangzhou Zhejiang Province China 310009
| | - Xue Li Bai
- the Second Affiliated Hospital, School of Medicine, Zhejiang University; Department of Hepatobiliary and Pancreatic Surgery; 88 Jiefang Road Hangzhou Zhejiang Province China 310009
| | - Wei Chen
- the Second Affiliated Hospital, School of Medicine, Zhejiang University; Department of Hepatobiliary and Pancreatic Surgery; 88 Jiefang Road Hangzhou Zhejiang Province China 310009
| | - Tao Ma
- the Second Affiliated Hospital, School of Medicine, Zhejiang University; Department of Hepatobiliary and Pancreatic Surgery; 88 Jiefang Road Hangzhou Zhejiang Province China 310009
| | - Hao Liu
- the Second Affiliated Hospital, School of Medicine, Zhejiang University; Department of Hepatobiliary and Pancreatic Surgery; 88 Jiefang Road Hangzhou Zhejiang Province China 310009
| | - Yun Zhang
- the Second Affiliated Hospital, School of Medicine, Zhejiang University; Department of Hepatobiliary and Pancreatic Surgery; 88 Jiefang Road Hangzhou Zhejiang Province China 310009
| | - Xiao Jun Hu
- Zhejiang University; Center for Medical Information; 388 Yuhangtang Road Hangzhou China
| | - Ting Bo Liang
- the Second Affiliated Hospital, School of Medicine, Zhejiang University; Department of Hepatobiliary and Pancreatic Surgery; 88 Jiefang Road Hangzhou Zhejiang Province China 310009
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Chen X, Zhang B, Yin X, Ren Z, Qiu S, Zhou J. Lipiodolized transarterial chemoembolization in hepatocellular carcinoma patients after curative resection. J Cancer Res Clin Oncol 2013; 139:773-81. [PMID: 23377952 DOI: 10.1007/s00432-012-1343-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2012] [Accepted: 10/22/2012] [Indexed: 12/28/2022]
Abstract
PURPOSE To explore the effect of lipiodolized transarterial chemoembolization (lip-TACE) in hepatocellular carcinoma (HCC) patients at different risk of recurrence after curative resection. METHODS One thousand nine hundred and twenty-four consecutive HCC patients who underwent curative resection were retrospectively analyzed. Patients who underwent resection only were classified into control group, while those received adjuvant lip-TACE were classified into intervention group. Patients were further stratified into 4 groups, that is, tumor ≤5 cm with low or high risk factors, as well as tumor >5 cm with low or high risk factors for recurrence. Tumor number and microscopic tumor thrombus were defined as risk factors for recurrence. The effect of adjuvant lip-TACE on early (<2 year) or late (≥2 year) recurrence was evaluated. RESULTS There was no significant difference in recurrence curve between intervention group and control group in each stratum. Adjuvant lip-TACE showed an overall survival benefit in patients with tumor >5 cm and presenting high risk factors, mainly for those with time to recurrence (TTR) <2 years after operation. For them, the median survival was 17 months in the intervention group and 11 months in the control group (P = 0.010). For patients who were confirmed to be recurrence-free at 2 years after operation, it had the negative effect for survival (HR = 1.75, P = 0.004). CONCLUSION Adjuvant lip-TACE had no preventive effect on recurrence, but may be of benefit to detect early recurrence.
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Zhong JH, Li H, Li LQ, You XM, Zhang Y, Zhao YN, Liu JY, Xiang BD, Wu GB. Adjuvant therapy options following curative treatment of hepatocellular carcinoma: a systematic review of randomized trials. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2012; 38:286-295. [PMID: 22281155 DOI: 10.1016/j.ejso.2012.01.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2011] [Revised: 12/28/2011] [Accepted: 01/05/2012] [Indexed: 01/27/2023]
Abstract
AIMS Numerous postoperative therapies for preventing recurrence of hepatocellular carcinoma (HCC) have been reported, but their efficacy remains controversial and knowledge about adverse effects is limited. A systematic review of randomized controlled trials (RCTs) was performed to gain a comprehensive picture of the efficacy and risks of these therapies. METHODS MEDLINE, EMBASE and the Cochrane Library were systematically searched through July 2011. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS A total of 2989 patients from 28 RCTs involving 10 postoperative therapies were included. For interferon therapy, the estimated RR for the 2-year recurrence rate was 0.84 (95% CI 0.73-0.97, P = 0.02) and the overall survival (OS) was 1.15 (95% CI 1.07-1.22, P < 0.001). Postoperative therapy with the vitamin K2 analog did not lead to a significant reduction in the 1-year recurrence rate, with a pooled RR of 0.60 (95% CI 0.28-1.27, P = 0.18). However, it did slightly improve the 1-year OS, with a pooled RR of 1.03 (95% CI 1.00-1.05, P = 0.03). Transarterial chemotherapy with or without embolization, adoptive immunotherapy and heparanase inhibitor PI-88 therapy may delay tumor recurrence. The effects of acyclic retinoid, lipiodol-iodine-131 and tumor vaccine treatment were promising but require further study. All postoperative therapies except interferon administered intramuscularly were well tolerated by the majority of patients. CONCLUSIONS Use of adjuvant interferon is definitely associated with an increase in OS. Postoperative therapies involving acyclic retinoid, lipidol-iodine-131, or tumor vaccine may improve the OS of patients with HCC after curative treatment.
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Affiliation(s)
- J-H Zhong
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, He Di Rd. #71, Nanning 530021, PR China
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Palesty JA, Al-Kasspooles M, Gibbs JF. Patient selection for surgical management of primary and metastatic liver cancers: current perspectives. Semin Intervent Radiol 2011; 23:13-20. [PMID: 21326716 DOI: 10.1055/s-2006-939837] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The surgical management of liver malignancies remains a mainstay in the treatment of such patients, and has benefited from dramatic advancements over the last two decades. Improvements in surgical technique, better understanding of hepatic anatomy, and improvement in anesthesiological supportive care has resulted in a decline in perioperative morbidity and operative mortality. Proper patient selection for surgical and nonsurgical treatment currently employs a multidisciplinary approach in our institution. This review will focus on the surgical treatment options for both primary and secondary liver cancers.
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Affiliation(s)
- J Alexander Palesty
- Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, New York
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Ueno M, Uchiyama K, Ozawa S, Hayami S, Shigekawa Y, Tani M, Yamaue H. Adjuvant chemolipiodolization reduces early recurrence derived from intrahepatic metastasis of hepatocellular carcinoma after hepatectomy. Ann Surg Oncol 2011; 18:3624-31. [PMID: 21614626 DOI: 10.1245/s10434-011-1800-6] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2011] [Indexed: 12/26/2022]
Abstract
BACKGROUND The recurrence of hepatocellular carcinoma is still high even after surgery. Two general recurrence patterns occur: intrahepatic metastasis (IM) and multicentric carcinogenesis (MC). The aim of this study was to investigate the effectiveness of adjuvant chemolipiodolization for reducing IM or MC recurrences after surgery. METHODS A retrospective case-control study was carried out. From April 2005, adjuvant chemolipiodolization was performed in 63 initial hepatocellular carcinoma patients 3 months after surgery. Sixty-four patients who underwent surgery between April 2001 and March 2005 were analyzed as the control group. Recurrence-free and overall survival as well as prognostic factors were analyzed univariately and multivariately. RESULTS The 2-year recurrence-free survival was 57% in the chemolipiodolization group and 37% in the control group (P = 0.02). However, there was no significant difference at 5 years after surgery (P = 0.09). The 5-year overall survival rates in the chemolipiodolization and the control groups were 82.4 and 55.7%, respectively (P = 0.04). Cox proportional multivariate analysis revealed that adjuvant chemolipiodolization was an independent favorable prognostic factor for 2-year recurrence-free survival, and the odds ratio [95% confidential interval] was 0.55 [0.34-0.90] (P = 0.02). However, adjuvant chemolipiodolization was not an independent favorable prognostic factor for 5-year overall survival. CONCLUSIONS Adjuvant chemolipiodolization can reduce the risk of early recurrences, which would be mainly IM derived. However, chemolipiodolization did not reduce late phase recurrences after surgery, which would be mainly MC derived. To prevent late phase recurrences, another novel strategy would be needed.
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Affiliation(s)
- Masaki Ueno
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama City, Japan
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Chen XH, Zhang BH, Xin Y, Ren ZG, Fan J, Qiu SJ, Zhou J. Risk factors for residual tumor after resection of hepatocellular carcinoma. World J Gastroenterol 2011; 17:1889-94. [PMID: 21528064 PMCID: PMC3080725 DOI: 10.3748/wjg.v17.i14.1889] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2010] [Revised: 09/25/2010] [Accepted: 10/02/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify the clinicopathological risk factors correlated with residual tumor in hepatocellular carcinoma (HCC) patients after resection.
METHODS: From January 2001 to April 2007, 766 HCC patients who had undergone resection were included in this research. Lipiodol angiography was performed within 2 mo after surgery and followed by post-Lipiodol computed tomography (CT) 4 wk later for all 766 patients to monitor tumor in the remnant liver. Tumor detected within the first 3-mo postoperative period was defined as residual tumor. Patients were divided into 2 groups: disease or disease-free within the first 3 mo after surgery. Risk factors for residual tumor were investigated among various clinicopathological variables.
RESULTS: A total of 63 (8.22%) patients were found to have residual tumor after surgery. Three independent factors associated with residual tumor were identified by multivariate analysis: preoperative serum α -fetoprotein (AFP) level [odds ratio (OR) = 1.68 (95% confidence interval (CI): 1.20-2.36)], tumor size [OR = 1.73 (95% CI: 1.29-2.31)] and microvascular invasion [OR = 1.91 (95% CI: 1.12-3.24)].
CONCLUSION: Residual tumor is related to AFP level, tumor size and microvascular invasion. Patients at high risk should undergo closer follow-up and could be candidates for multimodality therapy.
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Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011:CD004787. [PMID: 21412886 DOI: 10.1002/14651858.cd004787.pub2] [Citation(s) in RCA: 148] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC. OBJECTIVES To assess the beneficial and harmful effects of TACE or TAE. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Cancer Network register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The Latin American Caribbean Health Sciences Literature (LILACS) from dates of inceptions up to September 2010. SELECTION CRITERIA We considered for inclusion all randomised trials that compared TACE or TAE versus placebo, sham, or no intervention. Co-interventions were allowed if comparable between intervention groups. Trials with inadequate randomisation were excluded. DATA COLLECTION AND ANALYSIS For all-cause mortality, we calculated the log hazard ratio (HR) with standard error as point estimate and pooled them for meta-analysis using the inverse variance method. Sub-group analyses were performed regarding intervention regimen, trial truncation, or co-interventions. We validated the results with trial sequential analyses. We used random-effects model in all meta-analyses in anticipation of statistical heterogeneity among the trials. MAIN RESULTS We included nine trials with 645 participants. Six trials assessed TACE versus control and three trials assessed TAE versus control. Seven trials had low risk of selection bias based on adequate generation of allocation sequence and concealment - but all these trials had other risks of bias. Three trials were stopped early due to interim inspections and one due to slow accrual. For all-cause mortality, statistical heterogeneity between trials was low to moderate (I(2)= 30%). Meta-analysis of trials with low risk of selection bias showed that TACE or TAE versus control does not significantly increase survival (HR 0.88; 95% CI 0.71 to 1.10). Two trials with low risk of selection bias, no early stopping, and no co-intervention did not establish any significant effect of TACE or TAE on overall survival (hazard ratio 1.22, 95% confidence interval 0.82 to 1.83; P = 0.33). Trial sequential analysis confirmed the absence of evidence for a beneficial effect of TACE or TAE on survival indicating the need for future randomisation of up to 383 additional participants. Substantial differences in criteria for assessing tumour response did not allow quantitative analyses. One trial investigated quality of life but did not detect any significant differences between the intervention groups. A range of adverse events including post-embolisation syndrome and serious complications were reported. AUTHORS' CONCLUSIONS There is no firm evidence to support or refute TACE or TAE for patients with unresectable HCC. More adequately powered and bias-protected trials are needed.
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MESH Headings
- Antineoplastic Agents/administration & dosage
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/mortality
- Chemoembolization, Therapeutic/adverse effects
- Chemoembolization, Therapeutic/methods
- Chemoembolization, Therapeutic/mortality
- Embolization, Therapeutic/adverse effects
- Embolization, Therapeutic/methods
- Embolization, Therapeutic/mortality
- Humans
- Infusions, Intra-Arterial/adverse effects
- Infusions, Intra-Arterial/methods
- Liver Neoplasms/drug therapy
- Liver Neoplasms/mortality
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Affiliation(s)
- Roberto S Oliveri
- Department of Oncology, The Finsen Centre, section 5073, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100
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Masuda T, Beppu T, Horino K, Komori H, Hayashi H, Okabe H, Otao R, Horlad H, Ishiko T, Takamori H, Kikuchi K, Baba H. Preoperative tumor marker doubling time is a useful predictor of recurrence and prognosis after hepatic resection of hepatocellular carcinoma. J Surg Oncol 2010; 102:490-6. [PMID: 19937994 DOI: 10.1002/jso.21451] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND OBJECTIVES It is important to identify prognostic factors in patients with hepatocellular carcinoma (HCC) before hepatectomy. No previous studies have addressed the predictive efficacy of the preoperative doubling times of alpha-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKA-II). METHODS A total of 210 HCC patients who underwent a hepatic resection between 1998 and 2006 were prospectively evaluated. Serum AFP and PIVKA-II levels were measured at least twice before surgery to calculate the doubling times. Nineteen clinical factors that can be examined preoperatively, including the doubling times of AFP and PIVKA-II were investigated to identify prognostic factors for disease-free and overall survival after hepatectomy. RESULTS There was no relationship between preoperative levels and doubling times of AFP and PIVKA-II. In a multivariate analysis, patients with a doubling time of AFP ≤30 days and PIVKA-II ≤16 days showed a significantly worse disease-free (P = 0.02, P = 0.03, respectively) and overall survival (P < 0.0001, P = 0.03, respectively). CONCLUSIONS In HCC patients, the doubling times of preoperative serum AFP or PIVKA-II levels are useful tools to predict early postoperative recurrence and a poor prognosis.
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Affiliation(s)
- Toshiro Masuda
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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Zhong JH, Li LQ. Postoperative adjuvant transarterial chemoembolization for participants with hepatocellular carcinoma: A meta-analysis. Hepatol Res 2010; 40:943-953. [PMID: 20887328 DOI: 10.1111/j.1872-034x.2010.00710.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
AIM The efficacy of transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC) is positive, but for postoperative HCC, many studies have reported controversial results. The present study aimed to evaluate the efficacy of postoperative adjuvant TACE for participants with HCC. METHODS Electronic and manual searches were conducted to identify randomized controlled trials (RCT) evaluating postoperative adjuvant TACE for participants with HCC. RESULTS Six RCT totaling 659 participants, of whom almost all were of stage IIIA HCC, were included. For the 1-year tumor recurrence rate, hepatectomy plus TACE showed statistically significant less incidence of recurrence, with a pooled risk ratio (RR) of 0.68 (95% confidence interval [CI] = 0.55-0.84, P = 0.0003). For 1-year mortality, the trials were favorable for TACE with a pooled risk ratio of 0.48 (95% CI = 0.35-0.65, P < 0.00001). For 3-year mortality, the trials also revealed statistically significant less incidence, with a pooled risk ratio of 0.76 (95% CI = 0.64-0.90, P = 0.002). However, for 5-year mortality, TACE did not demonstrate statistically significant less incidence (RR = 0.94, 95% CI = 0.81-1.08, P = 0.36). Transient fever and nausea/vomiting were reported as side-effects of TACE but were well tolerated by most participants. CONCLUSION Postoperative adjuvant TACE seems promising for participants with HCC with risk factors (multiple nodules of >5 cm or vascular invasion) but requires further trial.
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Affiliation(s)
- Jian-Hong Zhong
- Hepatobiliary Surgery Department, Tumor Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
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Zhong C, Guo RP, Li JQ, Shi M, Wei W, Chen MS, Zhang YQ. A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma. J Cancer Res Clin Oncol 2009; 135:1437-45. [PMID: 19408012 DOI: 10.1007/s00432-009-0588-2] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2008] [Accepted: 04/08/2009] [Indexed: 12/15/2022]
Abstract
PURPOSE Hepatectomy is considered as the potentially curative treatment for hepatocellular carcinoma (HCC) and used in some selected Stage IIIA HCC, which include multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s) (UICC TNM staging system, sixth edition). Transcatheter arterial chemoembolization (TACE) was used in retrospective studies to improve the survival outcome of resected HCC. However, its beneficial effect on the survival outcomes of the Stage IIIA patients has not been evaluated. The present study is to evaluate if hepatectomy combining with adjuvant TACE for Stage IIIA HCC result in better long-term survival outcome when compared with hepatectomy alone. METHODS From January 2001 to March 2004, we conducted a prospective randomized trial in patients with Stage IIIA HCC (NCT00652587), recruiting 115 Stage IIIA HCC patients to undergo hepatectomy with adjuvant TACE (HT arm) or to undergo hepatectomy alone (HA arm) in our cancer center. Survival outcomes of the two arms were analyzed. RESULTS The demographic data were well matched between the two arms. There were no significant differences in the morbidity and in-hospital mortality between the two arms of patients. The most significant toxicities associated with adjuvant TACE were nausea/vomiting (54.4%) and transient hepatic toxicity (elevation of aminotransferase, 52.6%). Although there was no significant difference in the rate of recurrence between the two arms (50/57 vs. 56/58, P = 0.094), HT arm seemed to have more proportion of single lesion of recurrent HCC (chi (2) = 3.719, P = 0.054) and more proportion of potential curative therapy for recurrence (chi (2) = 4.456, P = 0.035). Until the time of censor, 92 patients had died. The 1-, 3-, and 5-year overall survival rates and median overall survival for HT arm were 80.7, 33.3, 22.8% and 23.0 months, respectively. The corresponding overall survival rates and median overall survival for HA arm were 56.5, 19.4, 17.5% and 14.0 months, respectively. The difference was significant (stratified log-rank test, P = 0.048). The 1-, 3-, and 5-year disease-free survival rates and median disease-free survival for HT arm were 29.7, 9.3, 9.3% and 6.0 months, respectively; correspondingly, for HA arm were 14.0, 3.5, 1.7% and 4.0 months, respectively (stratified log-rank test, P = 0.004). CONCLUSIONS For Stage IIIA HCC, hepatectomy with adjuvant TACE efficaciously and safely improved survival outcomes when compared with hepatectomy alone.
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Affiliation(s)
- Chong Zhong
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
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Multimodal approaches to the treatment of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2009; 6:159-69. [DOI: 10.1038/ncpgasthep1357] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2008] [Accepted: 12/17/2008] [Indexed: 02/16/2023]
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Marelli L, Stigliano R, Triantos C, Senzolo M, Cholongitas E, Davies N, Yu D, Meyer T, Patch DW, Burroughs AK. Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. Cancer Treat Rev 2006; 32:594-606. [PMID: 17045407 DOI: 10.1016/j.ctrv.2006.08.002] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2006] [Accepted: 08/20/2006] [Indexed: 12/30/2022]
Abstract
BACKGROUND Although transarterial chemoembolization (TACE) improves survival in patients with hepatocellular carcinoma (HCC), it is not known if TACE combined with other treatments is beneficial. AIM To evaluate the evidence for improved outcomes in HCC with a multimodal treatment approach involving TACE. METHOD PubMed search for all cohort and randomized trials (n=84) evaluating TACE combined with other therapies; meta-analysis performed where appropriate. RESULTS A meta-analysis involving 4 RCTs showed a significant decrease in mortality favouring combination treatment (TACE plus percutaneous ablation) compared to monotherapy in patients with either small (<3cm) or large HCC nodules (>3cm) (OR, 0.534; 95% CI, 0.288-0.990; p=0.046). TACE combined with local radiotherapy improved survival in patients with tumour thrombosis of the portal vein in 7 non-randomized studies. Two RCTs and 13 non-randomized studies showed that TACE prior to hepatic resection does not improve survival nor tumour recurrence. Conversely, 2 RCTs and 5 comparative studies showed that transarterial injection of chemotherapeutic drugs mixed with lipiodol (TOCE) following hepatectomy confers survival benefit and less tumour recurrence. TACE before liver transplantation is safe and reduces drop-out rate from the waiting list, but there is no current evidence of improvement in subsequent survival or recurrence rate. CONCLUSIONS A combined approach involving TACE and percutaneous ablation improves survival. Adjuvant TOCE improves outcome after hepatectomy. TACE is useful to control tumours burden while on the waiting list for OLT. Multimodal treatment seems to be the best way to optimize TACE outcomes in HCC.
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Affiliation(s)
- Laura Marelli
- Liver Transplantation and Hepatobiliary Medicine Unit, Royal Free Hospital, Pond Street, NW3 2QG London, UK.
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Abstract
Over the past twenty-five years, hepatic resection has evolved from a high risk, resource-intensive procedure with limited application to a safe and commonly performed operation with broad indications. This period has seen dramatic improvements in perioperative outcome, including reductions in mortality, blood loss, transfusion rates, and hospital stay. These improved perioperative results are largely responsible for the emergence of hepatic resection as a viable and effective treatment option for selected patients with 1 degree and 2 degrees hepatobiliary malignancy. Continued advances in imaging technology, along with a heightened awareness of the clinical and tumor-related variables that dictate outcome, have allowed better preoperative assessment of disease extent and improved patient selection. Advances in other areas, such as minimally invasive and ablative techniques, have increased the treatment options and have had some impact on the approach to patients with malignant hepatobiliary disease; however, resection remains the most effective therapy. Although the long term results after resection are better than with other modalities, recurrence rates remain high, and further improvements in survival will require more effective systemic agents. As better adjuvant and neo-adjuvant therapies emerge, the results of resection are likely to improve and the indications for its application perhaps will extend to patients currently considered to have unresectable disease.
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Affiliation(s)
- David A Kooby
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA
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Shi M, Zhang CQ, Zhang YQ, Liang XM, Li JQ. Micrometastases of solitary hepatocellular carcinoma and appropriate resection margin. World J Surg 2004; 28:376-81. [PMID: 15022021 DOI: 10.1007/s00268-003-7308-x] [Citation(s) in RCA: 137] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
We studied the pattern of intrahepatic micrometastases using large pathologic sections on liver resection specimens with ample resection margins from 113 patients with a solitary hepatocellular carcinoma (HCC). The liver tissues around the HCC were divided into proximal and distal areas according to the direction of the portal vein flow. These areas were further divided into zones based on fixed criteria. Altogether, 273 micrometastases were identified, including 254 (93.0%) intravascular micrometastases and 19 (7.0%) tumor satellite micronodules. The distance of spread of these micrometastases ranged from 0.05 to 6.10 cm. The number of micrometastases was less in the proximal area than in the distal area. In addition, the farther the distance away from the primary tumor, the fewer micrometastases there were. Micrometastases extended beyond the 2 cm margin in only nine (8.0%) patients. In conclusion, micrometastases could spread via invasion of portal vein branches at an early stage even when the tumor was solitary and small. Anatomic segment resection is preferred for patients with a solitary HCC. Nonanatomic resection may be used as an alternative in patients with impaired liver function, but adequate resection margins should be achieved. For HCCs < or = 3 cm, a proximal resection margin and a distal margin of 1.0 cm are recommended. For HCCs > 3 cm, a 1.0 proximal resection margin and a 2.0 cm distal margin are recommended.
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Affiliation(s)
- Ming Shi
- Department of Hepatobiliary Disorders, Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, 510060 Guangzhou, Peoples Republic of China.
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Mathurin P, Raynard B, Dharancy S, Kirzin S, Fallik D, Pruvot FR, Roumilhac D, Canva V, Paris JC, Chaput JC, Naveau S. Meta-analysis: evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma. Aliment Pharmacol Ther 2003; 17:1247-61. [PMID: 12755838 DOI: 10.1046/j.1365-2036.2003.01580.x] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
AIM To evaluate adjuvant modalities after curative resection for hepatocellular carcinoma using a meta-analysis of randomized and non-randomized controlled trials. METHODS In a first step, a meta-analysis of randomized controlled trials was carried out. Sensitivity analyses after inclusion of non-randomized controlled trials were performed. Four therapeutic modalities were evaluated: pre-operative transarterial chemotherapy, post-operative transarterial chemotherapy, systemic chemotherapy and a combination of systemic and transarterial chemotherapy. RESULTS Only post-operative transarterial chemotherapy improved survival significantly at 2 years [difference, 22.8%; confidence interval (CI), 8.6-36.9%; P = 0.002] and 3 years (difference, 27.6%; CI, 8.2-47.1%; P = 0.005), and decreased the probability of no recurrence at 1 year (difference, 28.8%; CI, 16.7-40.8%; P < 0.001), 2 years (difference, 27.6%; CI, 8.2-47.1%; P = 0.005) and 3 years (difference, 28%; CI, 8.2-47.9%; P = 0.006). In a sensitivity analysis after inclusion of non-randomized controlled trials, post-operative transarterial chemotherapy still improved survival at 1 year (difference, 9.6%; CI, 0.8-18.3%; P = 0.03), 2 years (difference, 13.5%; CI, 0.9-26%, P = 0.04) and 3 years (difference, 18%; CI, 7-28.9%; P < 0.001), and decreased the probability of no recurrence at 1 year (difference, 20.3%; CI, 7.7-33%; P = 0.002), 2 years (difference, 35%; CI, 21.4-46.3%; P < 0.001) and 3 years (difference, 34.5%; CI, 18.7-50.3%; P < 0.001). CONCLUSION Post-operative transarterial chemotherapy improved survival and decreased the cumulative probability of no recurrence. New randomized controlled trials evaluating this modality are required.
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Affiliation(s)
- P Mathurin
- Service d'Hépatogastroentérologie, Hôpital Claude Hurriez, CHRU Lille, France.
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Abstract
Minimally invasive therapies are gaining increasing attention as an alternative to standard surgical therapies in the treatment of primary hepatocellular carcinoma. These include therapies administered transcatheterally (arterial embolization, intraarterial chemoinfusion, and combination chemoembolization) and percutaneously (chemical ablation with ethanol or acetic acid, and thermal ablation with radiofrequency, microwave, or laser energies). Benefits over surgical resection include the anticipated reduction in morbidity and mortality, low cost, suitability for real time image guidance, the ability to perform ablative procedures on outpatients, and the potential application in a wider spectrum of patients, including nonsurgical candidates. This review examines reported clinical success, potential complications, current limitations, and future directions of development of chemoembolization, ethanol and acetic acid instillation, and radiofrequency, microwave, and laser thermal ablation.
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Affiliation(s)
- S Nahum Goldberg
- Minimally Invasive Tumor Therapy Laboratory, Department of Radiology, Beth Israel Deaconess medical Center, Harvard Medical School, Boston Massachusetts 02215, USA.
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Martin RCG, Jarnagin WR. Randomized clinical trials in hepatocellular carcinoma and biliary cancer. Surg Oncol Clin N Am 2002; 11:193-205, x. [PMID: 11930874 DOI: 10.1016/s1055-3207(03)00081-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Primary hepatocellular carcinoma (HCC) remains among the most common malignancies in the world. Many of the advances in the treatment of this disease have come from combinations of early detection in endemic areas, improved radiologic evaluation in defining extent of disease, an increased use of nonsurgical treatment and improvements in surgical technique.
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Affiliation(s)
- Robert C G Martin
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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Results of hepatectomy for 600 cases with primary liver cancer. Chin J Cancer Res 1996. [DOI: 10.1007/bf02674969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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