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1
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Gundavda KK, Patkar S, Varty GP, Shah N, Velmurugan K, Goel M. Liver Resection for Hepatocellular Carcinoma: Recent Advances. J Clin Exp Hepatol 2025; 15:102401. [PMID: 39286759 PMCID: PMC11402310 DOI: 10.1016/j.jceh.2024.102401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 08/06/2024] [Indexed: 09/19/2024] Open
Abstract
Hepatocellular carcinoma (HCC) represents a significant global health burden. Surgery remains a cornerstone in the curative treatment of HCC, and recent years have witnessed notable advancements aimed at refining surgical techniques and improving patient outcomes. This review presents a detailed examination of the recent innovations in HCC surgery, highlighting key developments in both surgical approaches and adjunctive therapies. Advanced imaging technologies have revolutionized preoperative assessment, enabling precise tumour localization and delineation of vascular anatomy. The use of three-dimensional rendering has significantly augmented surgical planning, facilitating more accurate and margin-free resections. The advent of laparoscopic and robotic-assisted surgical techniques has ushered in an era of minimal access surgery, offering patients the benefits of shorter hospital stays and faster recovery times, while enabling equivalent oncological outcomes. Intraoperative innovations such as intraoperative ultrasound (IOUS) and fluorescence-guided surgery have emerged as valuable adjuncts, allowing real-time assessment of tumour extent and aiding in parenchyma preservation. The integration of multimodal therapies, including neoadjuvant and adjuvant strategies, has allowed for 'bio-selection' and shown the potential to optimize patient outcomes. With the advent of augmented reality and artificial intelligence (AI), the future holds immense potential and may represent significant strides towards optimizing patient outcomes and refining the standard of care.
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Affiliation(s)
- Kaival K Gundavda
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Gurudutt P Varty
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Niket Shah
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Karthik Velmurugan
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Mahesh Goel
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
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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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Hu L, Zheng Y, Lin J, Shi X, Wang A. Does adjuvant hepatic artery infusion chemotherapy improve patient outcomes for hepatocellular carcinoma following liver resection? A meta-analysis. World J Surg Oncol 2023; 21:121. [PMID: 37013589 PMCID: PMC10069128 DOI: 10.1186/s12957-023-03000-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 03/22/2023] [Indexed: 04/05/2023] Open
Abstract
BACKGROUND Adjuvant hepatic artery infusion chemotherapy (HAIC) has been shown to be beneficial to the patient outcomes in hepatocellular carcinoma (HCC). METHODS Randomized controlled trials (RCTs) and non-RCTs were identified from six databases up to January 26, 2023. Patient outcomes were assessed using overall survival (OS) and disease-free survival (DFS). Data were presented as hazard ratios (HR, 95% confidence intervals, or CIs). RESULTS The present systematic review included 2 RCTs and 9 non-RCTs with a total of 1290 cases. Adjuvant HAIC improved OS (HR of 0.69; 95% CI of 0.56-0.84; p < 0.01) and DFS (HR of 0.64; 95% CI of 0.49-0.83; p < 0.01). Subgroup analysis showed that HCC patients with portal vein invasion (PVI) or microvascular invasion (MVI) benefit from adjuvant HAIC in terms of OS ((HR of 0.43; 95% CI of 0.19-0.95; p < 0.01) and (HR of 0.43; 95% CI of 0.19-0.95; p = 0.0373), respectively) and DFS ((HR of 0.38; 95% CI of 0.21-0.69; p < 0.01) and (HR of 0.73; 95% CI of 0.60-0.88; p = 0.0125), respectively). Adjuvant HAIC with the oxaliplatin-based approach significantly improved OS (HR of 0.60; 95% CI of 0.36-0.84; p = 0.02) and (HR of 0.59; 95% CI of 0.43-0.75; p < 0.01), respectively). CONCLUSION This meta-analysis demonstrated that postoperative adjuvant HAIC was beneficial in HCC patients with PVI and MVI. It remains unclear whether HAIC can improve the survival outcome in all HCC patients after hepatic resection.
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Affiliation(s)
- Lingbo Hu
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China
- Department of Hepatopancreatobiliary Surgery, Taizhou Enze Medical Center (Group), Enze Hospital, Zhejiang, China
| | - Yu Zheng
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
| | - Jiangyin Lin
- Department of Blood Purification, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China
| | - Xingpeng Shi
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China
- Department of Hepatopancreatobiliary Surgery, Taizhou Enze Medical Center (Group), Enze Hospital, Zhejiang, China
| | - Aidong Wang
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China.
- Department of Hepatopancreatobiliary Surgery, Taizhou Enze Medical Center (Group), Enze Hospital, Zhejiang, 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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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: 15] [Impact Index Per Article: 3.8] [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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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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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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Nakada S, Allard MA, Lewin M, Awad S, Dahbi N, Nitta H, Cunha AS, Castaing D, Vibert E, Cherqui D, Miyazaki M, Ohtsuka M, Adam R. Ischemic Cholangiopathy Following Transcatheter Arterial Chemoembolization for Recurrent Hepatocellular Carcinoma After Hepatectomy: an Underestimated and Devastating Complication. J Gastrointest Surg 2020; 24:2517-2525. [PMID: 31754989 DOI: 10.1007/s11605-019-04409-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 09/10/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Ischemic cholangiopathy (IC) has a known poor prognosis. However, the risks and outcomes of this complication after transcatheter arterial chemoembolization (TACE) in hepatectomized patients are poorly documented. This study aimed to evaluate the incidence of and to identify the predictive factors for IC following TACE for recurrent hepatocellular carcinoma (HCC) after hepatectomy. METHOD From a cohort with a total of 486 patients who underwent resection for HCC, we included all consecutive patients who were treated with TACE for recurrent HCC after hepatectomy between 2000 and 2017. IC was defined by the coexistence of biological cholestasis and morphological lesions. RESULTS A total of 156 patients underwent TACE for the treatment of HCC recurrence after hepatectomy. Of them, eight (5.1%) developed IC. Their prognosis was poor compared with patients without IC (3-year survival 23.4% vs 76.2%; P = 0.008). Two factors, namely, time between hepatectomy and TACE (4.8 months vs. 16.0 months, P = 0.001) and TACE for a remnant liver mobilized during hepatectomy (P = 0.001), were associated with IC. Receiver operating characteristic (ROC) curve analysis showed that 7 months was the more discriminant cutoff for the time period. IC occurred in 33.3% of the patients with the two factors, in 5.0% of those with one factor, and 0% in the absence of any factors. CONCLUSION TACE for treating HCC recurrence carries a high risk of IC when performed early after hepatectomy in a previously mobilized liver. Our results might aid in identifying candidates for TACE for recurrent HCC, considering the major effect on patient outcomes.
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Affiliation(s)
- Shinichiro Nakada
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France.,Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Marc-Antoine Allard
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - Maite Lewin
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - Sameh Awad
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - Nour Dahbi
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - Hidetoshi Nitta
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France.,Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Antonio Sa Cunha
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - Denis Castaing
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - Eric Vibert
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - Daniel Cherqui
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - Masaru Miyazaki
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.,Department of Gastroenterological Surgery, Mita Hospital International University of Health & Welfare, Tokyo, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - René Adam
- AP-HP Hôpital Paul-Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France. .,Centre Hépato-Biliaire, 9 Avenue Paul Vaillant Couturier, 94804, Villejuif, France.
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12
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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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13
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Li L, Li B, Zhang M. Postoperative adjuvant transarterial chemoembolization improves the prognosis of hepatocellular carcinoma patients with microvascular invasion: a systematic review and meta-analysis. Acta Radiol 2020; 61:723-731. [PMID: 31594382 DOI: 10.1177/0284185119878357] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Microvascular invasion has been widely accepted as a major risk factor of hepatocellular carcinoma prognoses after surgery. It is still controversial whether postoperative adjuvant transarterial chemoembolization could improve the survival of hepatocellular carcinoma patients with microvascular invasion. PURPOSE To evaluate the effect of postoperative adjuvant transarterial chemoembolization for postoperative hepatocellular carcinoma patients with microvascular invasion. MATERIAL AND METHODS PubMed, Web of Science, and Embase databases were searched for eligible studies, and the one-, three-, and five-year recurrence rates and overall survival rates were extracted for meta-analysis. RESULTS A total of eight studies were included in this study. The results showed that the one-, three-, and five-year recurrence rate of the postoperative adjuvant transarterial chemoembolization group were better than those of the hepatectomy alone group, with a pooled risk ratio (RR) of 0.66 (95% confidence interval [CI] 0.58-0.75, P < 0.00001), 0.82 (95% CI 0.76-0.88, P < 0.00001), and 0.89 (95% CI 0.82-0.97, P = 0.007), respectively. The overall survival rates with one-, three-, and five-year pooled RR were 0.34 (95% CI 0.25-0.47, P < 0.00001), 0.69 (95% CI 0.60-0.79, P < 0.00001), and 0.78 (95% CI 0.69-0.89, P = 0.0001), respectively. No serious side effects have been reported, indicating that postoperative intervention is safe. CONCLUSION For hepatocellular carcinoma patients with microvascular invasion confirmed by postoperative pathology, postoperative adjuvant transarterial chemoembolization is a safe treatment, which could reduce the tumor recurrence rate and improve the patient's overall survival.
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Affiliation(s)
- Lian Li
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Bo Li
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Ming Zhang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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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: 18] [Impact Index Per Article: 3.6] [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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Liu S, Li H, Guo L, Zhang B, Zhou B, Zhang W, Zhou J, Fan J, Ye Q. Tumor Size Affects Efficacy of Adjuvant Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma and Microvascular Invasion. Oncologist 2018; 24:513-520. [PMID: 30552155 DOI: 10.1634/theoncologist.2018-0305] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 10/16/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) and microvascular invasion (mVI) have shown dismal postoperative prognosis; however, whether adjuvant transarterial chemoembolization (TACE) can improve their outcomes remains unclear. MATERIALS AND METHODS We retrospectively identified 549 eligible patients to form the crude cohort and adopted propensity score matching method to assemble another cohort of 444 patients with similar baseline characteristics. We assessed the effects of adjuvant TACE by stratified analyses and multivariate Cox analyses in two cohorts. RESULTS There was significant interaction between tumor size and adjuvant TACE with respect to overall survival (OS; p = .006 for interaction). In the matched cohort, patients who received adjuvant TACE showed higher rates of 5-year OS (72.4% vs. 50.9%, p = .005) and 5-year recurrence-free survival (50.5% vs. 36.4%, p = .003) in the tumor ≤5 cm subgroup, but not in the tumor >5 cm subgroup (32.3% vs. 24.9%, p = .350 and 18.8% vs. 19.7%, p = .180). The independent protective role of adjuvant TACE on OS was observed in patients with tumor ≤5 cm (adjusted odds ratio [OR] = 0.59, 95% confidence interval [CI] 0.36-0.97) but not in patients with tumor >5 cm (adjusted OR = 1.17, 95% CI 0.84-1.62). The effects of adjuvant TACE did not change materially while the analysis was performed in the crude cohort. CONCLUSION For patients with HCC and mVI, adjuvant TACE was associated with improved outcomes, but not for those with tumor >5 cm, according to the current protocol. IMPLICATIONS FOR PRACTICE The outcomes of patients with hepatocellular carcinoma and microvascular invasion who received adjuvant transarterial chemoembolization were inconsistent in this study. According to the current protocol, adjuvant transarterial chemoembolization was associated with improved prognosis in patients with microvascular invasion, except for those with tumor >5 cm. Multivariate Cox models confirmed adjuvant transarterial chemoembolization was an independent protective factor in the tumor ≤5 cm subgroup but not in the tumor >5 cm subgroup.
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Affiliation(s)
- Shuang Liu
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Hui Li
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Lei Guo
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Bo Zhang
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Binghai Zhou
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Wentao Zhang
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Jian Zhou
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Jia Fan
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Qinghai Ye
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
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18
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Liu S, Guo L, Li H, Zhang B, Sun J, Zhou C, Zhou J, Fan J, Ye Q. Postoperative Adjuvant Trans-Arterial Chemoembolization for Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus. Ann Surg Oncol 2018; 25:2098-2104. [DOI: 10.1245/s10434-018-6438-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Indexed: 12/23/2022]
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19
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Wang Z, Ren Z, Chen Y, Hu J, Yang G, Yu L, Yang X, Huang A, Zhang X, Zhou S, Sun H, Wang Y, Ge N, Xu X, Tang Z, Lau W, Fan J, Wang J, Zhou J. Adjuvant Transarterial Chemoembolization for HBV-Related Hepatocellular Carcinoma After Resection: A Randomized Controlled Study. Clin Cancer Res 2018; 24:2074-2081. [PMID: 29420221 DOI: 10.1158/1078-0432.ccr-17-2899] [Citation(s) in RCA: 201] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 12/14/2017] [Accepted: 01/30/2018] [Indexed: 02/06/2023]
Abstract
Purpose: The survival of patients with hepatocellular carcinoma (HCC) recurrence after curative resection is usually poor. We sought to evaluate the safety and efficacy of adjuvant transarterial chemoembolization (TACE) in HBV-related HCC patients with an intermediate (a single tumor larger than 5 cm without microvascular invasion) or high risk (a single tumor with microvascular invasion, or two or three tumors) of recurrence.Experimental Design: In this randomized phase 3 trial, 280 eligible patients were assigned to adjuvant TACE (n = 140) or no adjuvant treatment (control; n = 140) groups. The primary endpoint was recurrence-free survival (RFS); secondary endpoints included overall survival (OS) and safety. Multivariable Cox-proportional hazards model was used to determine the independent impact of TACE on patients' outcomes.Results: Patients who received adjuvant TACE had a significantly longer RFS than those in the control group [56.0% vs. 42.1%, P = 0.01; HR, 0.68; 95% confidence interval (CI), 0.49-0.93]. Patients in the adjuvant TACE group had 7.8% higher 3-year OS rate than the control group (85.2% vs. 77.4%; P = 0.04; HR, 0.59; 95% CI, 0.36-0.97). The impact of adjuvant TACE on RFS and OS remained significant after controlling for other known prognostic factors (HR, 0.67; P = 0.01 for RFS; and HR, 0.59; P = 0.04 for OS). There was no grade 3 or 4 toxicity after adjuvant TACE.Conclusions: For patients with HBV-related HCC who had an intermediate or high risk of recurrence after curative hepatectomy, our study showed adjuvant TACE significantly reduced tumor recurrence, improved RFS and OS, and the procedure was well tolerated. Clin Cancer Res; 24(9); 2074-81. ©2018 AACR.
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Affiliation(s)
- Zheng Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Zhenggang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Yi Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Jie Hu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Guohuan Yang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Lei Yu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Xinrong Yang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Ao Huang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Xin Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Shaolai Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Huichuan Sun
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Yanhong Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Ningling Ge
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Xiaoyu Xu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Zhaoyou Tang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Wanyee Lau
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
- Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, HKSAR, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
- Institute of Biomedical Sciences, Fudan University, Shanghai, China
- State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
| | - Jiping Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China.
- Division of Surgical Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China.
- Institute of Biomedical Sciences, Fudan University, Shanghai, China
- State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
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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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21
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Gao Z, Du G, Pang Y, Fu Z, Liu C, Liu Y, Zhou B, Kong D, Shi B, Jiang Z, Jin B. Adjuvant transarterial chemoembolization after radical resection contributed to the outcomes of hepatocellular carcinoma patients with high-risk factors. Medicine (Baltimore) 2017; 96:e7426. [PMID: 28816936 PMCID: PMC5571673 DOI: 10.1097/md.0000000000007426] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
We aim to investigate the effects of postoperative adjuvant transarterial chemoembolization (TACE) on survival and recurrence in hepatocellular carcinoma (HCC) patients after radical resection. A total of 320 HCC patients underwent radical resection between January 2010 and January 2014 in Qilu Hospital, Shandong University were divided into 4 groups according to the frequency of postoperative adjuvant TACE. Patients were further stratified into subgroups (tumor diameter ≤5 or >5 cm) with low or high risk factors for recurrence or death. A low risk factor for recurrence or death was defined as Edmondson grade I/II without microvascular invasion (MiVI), while a high risk factor was defined as Edmondson grade III/IV or with MiVI. Survival data and recurrence rates were compared using the Kaplan-Meier method. Uni- and multivariate analyses were based on the Cox proportional analysis. Compared to those received no TACE, patients underwent 2 (log-rank, χ = 9.054, P = .003) or 3 (log-rank, χ = 4.228, P = .04) TACE showed delayed recurrence. Patients received 2 or 3 TACE showed extended overall survival (OS) compared with the other patients. No statistical differences were found between all the disease-free survival (DFS) and OS in low-risk subgroups. In the patients of the high-risk subgroup with a tumor diameter of ≤5, those received 2 TACE showed delayed recurrence compared with those received no TACE, and TACE (twice or thrice) can improve OS. For those of the high-risk subgroup with a tumor diameter of >5, TACE (twice or thrice) can delay recurrence and improve OS. Adjuvant TACE (twice or thrice) after radical resection is beneficial for HCC patients with poor differentiation and MiVI, especially for those with a tumor diameter of >5 cm.
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Affiliation(s)
- Zhendong Gao
- Department of General Surgery, Qilu Hospital of Shandong University
- School of Medicine, Shandong University, Jinan
| | - Gang Du
- Department of General Surgery, Qilu Hospital of Shandong University
| | - Yuguang Pang
- Department of General Surgery, Renmin Hospital of Lingcheng, Dezhou, China
| | - Zhihao Fu
- Department of General Surgery, Qilu Hospital of Shandong University
- School of Medicine, Shandong University, Jinan
| | - Chongzhong Liu
- Department of General Surgery, Qilu Hospital of Shandong University
| | - Yi Liu
- Department of General Surgery, Qilu Hospital of Shandong University
| | - Binghai Zhou
- Department of General Surgery, Qilu Hospital of Shandong University
- School of Medicine, Shandong University, Jinan
| | - Du Kong
- Department of General Surgery, Qilu Hospital of Shandong University
- School of Medicine, Shandong University, Jinan
| | - Binyao Shi
- Department of General Surgery, Qilu Hospital of Shandong University
- School of Medicine, Shandong University, Jinan
| | - Zhengcheng Jiang
- Department of General Surgery, Qilu Hospital of Shandong University
- School of Medicine, Shandong University, Jinan
| | - Bin Jin
- Department of General Surgery, Qilu Hospital of Shandong University
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Kobayashi T, Aikata H, Kobayashi T, Ohdan H, Arihiro K, Chayama K. Patients with early recurrence of hepatocellular carcinoma have poor prognosis. Hepatobiliary Pancreat Dis Int 2017; 16:279-288. [PMID: 28603096 DOI: 10.1016/s1499-3872(16)60181-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Early recurrence (ER) after hepatic resection (HR) is a poor prognostic factor for patients with hepatocellular carcinoma (HCC). This study aimed to identify the clinicopathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern. METHODS We retrospectively examined 130 patients who underwent HR for small HCC (≤30 mm). Recurrence was classified into ER (<2 years) and late recurrence (LR) (≥2 years). The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis. RESULTS ER was observed in 39 patients (30.0%). The survival rate of the ER group was significantly lower than that of the LR group (P<0.005), and ER was an independent prognostic factor for poor survival (P=0.0001). The ER group had a significantly higher frequency (P=0.0039) and shorter interval (P=0.027) of development to carcinoma beyond the Milan criteria (DBMC) compared with the LR group, and ER was an independent risk factor for DBMC (P<0.0001). Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER (P=0.012, 0.010, and 0.019, respectively). CONCLUSIONS ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.
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Affiliation(s)
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan.
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Liao Y, Zheng Y, He W, Li Q, Shen J, Hong J, Zou R, Qiu J, Li B, Yuan Y. Sorafenib therapy following resection prolongs disease-free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence. Oncol Lett 2017; 13:984-992. [PMID: 28356989 PMCID: PMC5351299 DOI: 10.3892/ol.2016.5525] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Accepted: 05/13/2016] [Indexed: 01/27/2023] Open
Abstract
Sorafenib is the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC); however, its therapeutic value in patients with HCC following resection remains controversial. The current retrospective study was undertaken to assess the effects of sorafenib treatment following surgical resection in patients with advanced HCC disease who were at a high risk for recurrence. Between July 2010 and July 2013, a consecutive cohort of 42 patients with advanced HCC and at a high risk of recurrence (i.e., those with portal vein tumor thrombosis, adjacent organ involvement or tumor rupture) who underwent resection were analyzed. The patients were categorized into the sorafenib group (n=14) or the best supportive care (BSC) group (n=28). Although the histological grade, Barcelona Clinic Liver Cancer Stage, tumor size, nodule number and proportion of patients with high serum α-fetoprotein levels were comparable between the sorafenib and BSC groups, those receiving sorafenib following resection had significantly longer disease-free survival (DFS) of 5.2 months [95% confidence interval (CI), 1.2-9.2 months] compared with the BSC group [1.8 months (95% CI, 0.6-3.0 months)]. No differences in overall survival were noted between the groups. Furthermore, no drug-related adverse events resulted in discontinuation of sorafenib therapy. Univariate log-rank analysis revealed that sorafenib treatment (P=0.002) and treatment prior to resection (P=0.012) were significantly associated with longer DFS; however, sorafenib therapy (P=0.027) and tumor size (P=0.028) were associated with longer DFS by multivariate analysis. Furthermore, sorafenib was well-tolerated and improved DFS in patients with advanced HCC who underwent hepatic resection. Thus, tumor resection followed by sorafenib therapy may represent an effective therapeutic strategy for patients with advanced HCC. This possibility should be confirmed in larger, multicenter studies.
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Affiliation(s)
- Yadi Liao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Yun Zheng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Wei He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Qijiong Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Jingxian Shen
- Department of Medical Imaging and Interventional Center, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Jian Hong
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Ruhai Zou
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Jiliang Qiu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Binkui Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Yunfei Yuan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
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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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25
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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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Yuan Z, Zhao X, Zhao J, Pan G, Qiu W, Wang X, Zhu Y, Zheng Q, Cui W. Synergistic mediation of tumor signaling pathways in hepatocellular carcinoma therapy via dual-drug-loaded pH-responsive electrospun fibrous scaffolds. J Mater Chem B 2015; 3:3436-3446. [PMID: 32262226 DOI: 10.1039/c5tb00206k] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
A novel pH-sensitive electrospun composite PLLA fibrous scaffold was developed with long-term anti-cancer drug release and short-term anti-inflammation drug release for liver cancer therapy.
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Affiliation(s)
- Ziming Yuan
- Department of Orthopedics
- The First Affiliated Hospital of Soochow University
- Orthopedic Institute
- Soochow University
- Suzhou
| | - Xin Zhao
- Department of Orthopedics
- The First Affiliated Hospital of Soochow University
- Orthopedic Institute
- Soochow University
- Suzhou
| | - Jingwen Zhao
- Department of Orthopedics
- The First Affiliated Hospital of Soochow University
- Orthopedic Institute
- Soochow University
- Suzhou
| | - Guoqing Pan
- Department of Orthopedics
- The First Affiliated Hospital of Soochow University
- Orthopedic Institute
- Soochow University
- Suzhou
| | - Wangwang Qiu
- Department of General Surgery
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University
- School of Medicine
- Shanghai
- P. R. China
| | - Xiaohu Wang
- Department of General Surgery
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University
- School of Medicine
- Shanghai
- P. R. China
| | - Yueqi Zhu
- Department of General Surgery
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University
- School of Medicine
- Shanghai
- P. R. China
| | - Qi Zheng
- Department of General Surgery
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University
- School of Medicine
- Shanghai
- P. R. China
| | - Wenguo Cui
- Department of Orthopedics
- The First Affiliated Hospital of Soochow University
- Orthopedic Institute
- Soochow University
- Suzhou
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27
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Merle P, Rode A, Benlaredj R, Cuinet M, Said T, Bathaix F, Enachescu C, Mornex F. Efficacy and safety of transarterial chemoembolization combined to conformal radiotherapy for uninodular hepatocellular carcinoma. INTERNATIONAL JOURNAL OF CANCER THERAPY AND ONCOLOGY 2014. [DOI: 10.14319/ijcto.0204.10] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Zhong JH, Zhong QL, Li LQ, Li H. Adjuvant and chemopreventive therapies for resectable hepatocellular carcinoma: a literature review. Tumour Biol 2014; 35:9459-9468. [PMID: 25119592 DOI: 10.1007/s13277-014-2443-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Accepted: 08/04/2014] [Indexed: 01/27/2023] Open
Abstract
The recurrence rate of hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR) is very high. Many clinical trials have explored the efficacy of several treatment modalities to prevent recurrence, including adjuvant and chemopreventive therapy, but they have often reported contradictory findings. As a result, most liver guidelines and liver seminars do not unequivocally endorse adjuvant or chemopreventive therapy for HCC patients after potentially curative HR. To examine the available evidence on this question, we comprehensively searched PubMed for controlled studies that included a supportive care or placebo control arm, and we used the GRADE system to classify and assess the results.
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Affiliation(s)
- Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, He Di Rd. #71, Nanning, 530021, People's Republic of China
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Chau GY. Resection of hepatitis B virus-related hepatocellular carcinoma: Evolving strategies and emerging therapies to improve outcome. World J Gastroenterol 2014; 20:12473-12484. [PMID: 25253947 PMCID: PMC4168080 DOI: 10.3748/wjg.v20.i35.12473] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2013] [Revised: 01/28/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing worldwide, largely due to hepatitis B virus (HBV), hepatitis C virus and liver cirrhosis. Chronic HBV infection is estimated to cause 55%-60% of the cases of HCC worldwide and over 70% in Asian countries. Liver resection is currently the mainstay of treatment due to the low surgical mortality, a wider treatment indication, and simplicity of post-treatment follow-up. There is an ever-increasing demand on surgeons to perform curative liver resection in HCC, with the hope of avoiding tumor recurrences. Hepatitis B-related-HCC has distinct clinicopathological features, which should be considered when treating the disease. The author presents a review of the recently evolving strategies and emerging therapies to improve HCC postresectional outcomes and focus on perioperative measures to improve patient outcome, with particular reference to the current status of adjuvant therapies in HCC patients after liver resection.
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MESH Headings
- Antiviral Agents/therapeutic use
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/secondary
- Carcinoma, Hepatocellular/surgery
- Carcinoma, Hepatocellular/virology
- Chemotherapy, Adjuvant
- Hepatectomy/adverse effects
- Hepatectomy/methods
- Hepatectomy/mortality
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/mortality
- Humans
- Liver Neoplasms/mortality
- Liver Neoplasms/pathology
- Liver Neoplasms/surgery
- Liver Neoplasms/virology
- Neoplasm Recurrence, Local
- Neoplasm Staging
- Neoplasm, Residual
- Treatment Outcome
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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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Cratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel. (Hóng yá mù) extract induces apoptosis in human hepatocellular carcinoma HepG2 cells through caspase-dependent pathways. Chin Med 2014; 9:12. [PMID: 24708784 PMCID: PMC3985586 DOI: 10.1186/1749-8546-9-12] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2013] [Accepted: 04/04/2014] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Cratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel. (Hóng yá mù) (CF) has been used for treatment of fever, cough, and peptic ulcer. Previously, a 50% ethanol-water extract from twigs of CF was shown highly selective in cytotoxicity against cancer cells. This study aims to investigate the molecular mechanisms underlying the apoptosis-inducing effect of CF. METHODS The cytotoxicity of CF was evaluated in the human hepatocellular carcinoma (HCC) HepG2 cell line in comparison with a non-cancerous African green monkey kidney epithelial cell line (Vero) by a neutral red assay. The apoptosis induction mechanisms were investigated through nuclear morphological changes, DNA fragmentation, mitochondrial membrane potential alterations, and caspase enzyme activities. RESULTS CF selectively induced HepG2 cell death compared with non-cancerous Vero cells. A 1.5-fold higher apoptotic effect compared with melphalan was induced by 120 μg/mL of the 50% ethanol-water extract of CF. The apoptotic cell death in HepG2 cells occurred via extrinsic and intrinsic caspase-dependent pathways in dose- and time-dependent manners by significantly increasing the activities of caspase 3/7, 8, and 9, decreasing the mitochondrial membrane potential, and causing apoptotic body formation and DNA fragmentation. CONCLUSIONS CF extract induced a caspase-dependent apoptosis in HepG2 cells.
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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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Ochiai T, Yagi M, Igari K, Aihara A, Kumagai Y, Odajima H, Iida M, Tanaka S, Arii S, Yamazaki S. A Case of Recurrent “Icteric Type Hepatoma” Controlled by Anatomical Resection and Adjuvant Hepatic Arterial Chemotherapy. THE JAPANESE JOURNAL OF GASTROENTEROLOGICAL SURGERY 2013; 46:424-430. [DOI: 10.5833/jjgs.2012.0229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2025]
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Kobayashi T, Ishiyama K, Ohdan H. Prevention of recurrence after curative treatment for hepatocellular carcinoma. Surg Today 2012; 43:1347-54. [PMID: 23271667 DOI: 10.1007/s00595-012-0473-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Accepted: 10/26/2012] [Indexed: 12/22/2022]
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Nishikawa H, Osaki Y, Kita R, Kimura T, Inuzuka T, Takeda H, Nakajima J, Matsuda F, Sakamoto A, Henmi S, Hatamaru K, Saito S, Nasu A. Transcatheter arterial infusion chemotherapy prior to radiofrequency thermal ablation for single hepatocellular carcinoma reduces the risk of intrahepatic distant recurrence. Int J Oncol 2012; 41:903-9. [PMID: 22692851 DOI: 10.3892/ijo.2012.1512] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 05/11/2012] [Indexed: 01/17/2023] Open
Abstract
The aim of the present study was to elucidate the effectiveness of transcatheter arterial infusion chemotherapy (TAI) of the whole liver using an epirubicin-mitomycin-lipiodol emulsion, prior to radiofrequency thermal ablation (RFA), in preventing intrahepatic distant recurrence (IDR) from single hepatocellular carcinoma (HCC). Of the 269 consecutive patients who underwent RFA in our institute for single HCC, a total of 182 patients were analyzed in the present study. The primary endpoint was comparison of the post-RFA IDR-free survival rates in patients treated using TAI with an epirubicin-mitomycin-lipiodol emulsion via the proper hepatic artery (TAI-EML) prior to RFA, and patients that received lipiodol infusion-alone prior to RFA. The secondary endpoints were local tumor progression (LTP) and overall survival (OS). Lipiodol infusion-alone prior to RFA was performed in 88 patients and TAI-EML prior to RFA in 94 patients. The mean tumor size was 2.06 cm (range, 0.9-3.2 cm) in the TAI group and 1.97 cm (range, 0.9-3.3 cm) in the lipiodol-alone group, respectively. The cumulative IDR-free survival rates at 1, 2 and 3 years were 74.0, 50.8 and 34.9%, respectively, in the lipiodol-alone group, and 90.8, 74.8 and 70.0%, respectively, in the TAI group (P<0.001). In terms of the OS, there was a significant difference between these two groups (P=0.048), although there was no significant difference in terms of the LTP (P=0.145). We concluded that TAI-EML prior to RFA appears to be useful in reducing post-RFA IDR and may contribute to improved survival rates.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka 543-0027, Japan.
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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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Shen WF, Zhong W, Liu Q, Sui CJ, Huang YQ, Yang JM. Adjuvant transcatheter arterial chemoembolization for intrahepatic cholangiocarcinoma after curative surgery: retrospective control study. World J Surg 2011; 35:2083-91. [PMID: 21698503 DOI: 10.1007/s00268-011-1171-y] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Effects of adjuvant transcatheter arterial chemoembolization (TACE) for intrahepatic cholangiocarcinoma (ICC) radical surgery have never been evaluated. METHODS A retrospective analysis was conducted on 125 ICC patients who had undergone operations with curative intent in Shanghai Eastern Hepatobiliary Surgery Hospital from July 2002 to December 2003. Of these patients, 53 underwent adjuvant TACE (TACE group) and 72 did not (non-TACE group). Adjuvant TACE was performed one time 1.5-2.0 months after the operation. RESULTS Follow-up was performed at a median of 18 months (range 3-96 months). There was no significant recurrence-free survival (RFS) difference between the TACE and non-TACE groups (P = 0.659). The 1-, 3-, and 5-year overall survival (OS) rates were 69.8, 37.7, and 28.3%, respectively, for the TACE group and 54.2, 25.0, and 20.8%, respectively, for the non-TACE group (P = 0.045). Among 54 patients with a recurrence time of ≤ 3 months, the OS rate of the TACE group was better than that of the non-TACE group (P < 0.001). For 59 patients with a recurrence time later than the median RFS, no significant RFS difference was found between the TACE and non-TACE groups (P = 0.681). These results indicate that TACE could not delay recurrence but could prolong the OS of patients with early recurrence. CONCLUSIONS Adjuvant TACE after radical surgery was associated with better survival among the ICC patients with early recurrence.
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Affiliation(s)
- W F Shen
- Department of Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China
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Kim DY, Ahn SH, Kim SU, Choi SB, Lee KH, Park MS, Park JY, Lee DY, Han KH, Kim KS. Adjuvant hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin after curative resection of hepatocellular carcinoma. Oncology 2011; 81:184-191. [PMID: 22067673 DOI: 10.1159/000333827] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Accepted: 09/22/2011] [Indexed: 12/29/2022]
Abstract
OBJECTIVES We investigated whether adjuvant hepatic arterial infusional chemotherapy (HAIC) with 5-fluorouracil (5-FU) and cisplatin reduces the recurrence of hepatocellular carcinoma (HCC) after curative resection. METHODS Between January 2006 and December 2008, 31 HCC patients received four cycles of adjuvant HAIC with 5-FU and cisplatin via port system after curative resection. During the same period, 62 patients, who did not take any adjuvant therapy, were selected as controls. RESULTS Tumor characteristics, such as distribution of TNM stage, pathologic differentiation, portal vein invasion, or microscopic invasion did not differ between control and adjuvant groups. During follow-up, recurrence developed in 11 adjuvant (35.5%) and 24 control patients (38.7%; p = 0.823). Tumor progression after recurrence was the cause of death in 2 adjuvant (28.6%) and 7 control patients (38.8%; p = 0.912). The 2-year recurrence rate was 9.1% in the adjuvant group and 4.2% in the control group, with the median recurrence-free survival time being 10.5 and 7.5 months, respectively (p = 0.324). The 3-year cumulative survival rate was 73.3% in the adjuvant group and 68.3% in the control group (p = 0.355). CONCLUSION Adjuvant HAIC with 5-FU and cisplatin did not offer any beneficial effect on the recurrence after curative resection of HCC.
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Affiliation(s)
- Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea
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Kishi Y, Saiura A, Yamamoto J, Koga R, Seki M, Morimura R, Yoshioka R, Kokudo N, Yamaguchi T. Repeat treatment for recurrent hepatocellular carcinoma: is it validated? Langenbecks Arch Surg 2011; 396:1093-100. [PMID: 21847622 DOI: 10.1007/s00423-011-0837-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Accepted: 08/03/2011] [Indexed: 02/07/2023]
Abstract
PURPOSE Hepatocellular carcinoma (HCC) usually recurs repeatedly and locoregional treatment is attempted unless liver function has deteriorated. This study was aimed to evaluate the effect of repeated treatment on patient prognosis. METHODS The HCC recurrence pattern and types of treatment for recurrence after hepatic resection were reviewed in 134 patients. The effects of repeated treatment on prognosis were evaluated. Univariate and multivariate analyses were performed to determine the prognostic predictors after initial recurrence. RESULTS Median number of treatments after recurrence was 3 (range, 0-12). Transarterial chemoembolization was the most common treatment. The number of treatments, but not the type of treatment, was associated with the prognosis. Multivariate analysis showed that a >20% indocyanine green retention rate at 15 min (hazard ratio [HR] = 2.65; 95% confidential interval [CI], 1.53-5.62), size of primary tumor >5 cm (HR = 1.81; 95% CI, 1.05-3.08), recurrence-free interval <1 year (HR = 2.17; 95% CI, 1.28-3.81), size of recurrent tumor >3 cm (HR = 2.61; 95% CI, 1.03-5.77-0.95), and extrahepatic recurrence (HR = 6.35; 95% CI, 3.49-11.39) were independent predictors of poor survival. CONCLUSION The prognosis after recurrence is poor in cases with large tumors or poor liver function. Repeated locoregional treatment contributes to prolong patient prognosis, especially in cases with a small tumor size, long recurrence-free interval, and no extrahepatic metastases.
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Affiliation(s)
- Yoji Kishi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8500, Japan.
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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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Palmer D, Johnson PJ. Cytotoxic Chemotherapy and Endocrine Therapy for Hepatocellular Carcinoma. HEPATOCELLULAR CARCINOMA: 2011:337-353. [DOI: 10.1007/978-1-60327-522-4_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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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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Masuzaki R, Yoshida H, Omata M. Does chemotherapy prevent HCV-related hepatocellular carcinoma? Pros. Dig Liver Dis 2010; 42 Suppl 3:S281-6. [PMID: 20547315 DOI: 10.1016/s1590-8658(10)60517-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) infection, which seems to have spread worldwide recently, is now the leading cause of hepatocellular carcinoma (HCC) development in various geographic areas. The primary prevention of HCV-related HCC includes strategies for the prevention of HCV infection and those for viral eradication. Even after HCC development, short-term prognosis of patients has been much improved recently due to advances in early diagnosis and treatment. However, long-term prognosis is as yet far from satisfactory due to frequent recurrence of HCC even after apparently curative treatment, either local ablation or surgical resection. At least theoretically, strategies similar to those of primary prevention may be applicable to HCC recurrence. In this review, we summarized the reported favorable effects of chemotherapy on primary and tertiary prevention of HCC.
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Affiliation(s)
- Ryota Masuzaki
- Department of Gastroenterology, University of Tokyo, Tokyo, Japan
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Affiliation(s)
- Charles H Cha
- Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA
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Ng KM, Yan TD, Black D, Chu FCK, Morris DL. Prognostic determinants for survival after resection/ablation of a large hepatocellular carcinoma. HPB (Oxford) 2009; 11:311-20. [PMID: 19718358 PMCID: PMC2727084 DOI: 10.1111/j.1477-2574.2009.00044.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2008] [Accepted: 01/17/2009] [Indexed: 12/12/2022]
Abstract
BACKGROUND Liver resection of large hepatocellular carcinomas (HCC), measuring at least 10 cm remains a controversial debate. Multiple studies on HCCs treated with surgical resection and/or ablation had shown variable results with 5-year survival rates ranging from 0% to 54.0%. The aim of this study was to evaluate the survival of patients with HCCs measuring at least 10 cm and to identify the potential prognostic variables affecting the outcome. METHODS Retrospective analysis was performed on the prospectively updated HCC database. A total of 44 patients with tumours measuring 10 cm or more were 'curatively' treated with surgical resection with or without ablation. Patient demographics, clinical, surgical, pathology and survival data were collected and analysed. RESULTS Thirty-one patients received surgical resection alone. Thirteen other patients were treated with a combination of surgical resection and ablation. The median follow-up duration was 14.5 months. The overall median survival at 1, 3 and 5 years were 66.4%, 38.1% and 27.8%, respectively. The median time to tumour recurrence was 10.7 months and the 1, 3 and 5-year disease-free survival were 49.6%, 23.9% and 19.1%, respectively. Univariate analysis demonstrated cirrhosis, microvascular invasion, poor tumour differentiation and ethnicity to adversely affect survival. For overall survival, only cirrhosis, poor tumour differentiation and ethnicity were significant on multivariate analysis. Portal vein tumour thrombus, microvascular invasion and ethnicity were identified on univariate analysis to significantly affect disease-free survival. CONCLUSION Surgical treatment offers good survival to patients with large HCCs (> or = 10 cm). Both cirrhosis and poor tumour differentiation are independent variables prognostic of adverse survival.
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Affiliation(s)
- Keh M Ng
- Department of Surgery, University of New South Wales, St George HospitalSydney, NSW, Australia
| | - Tristan D Yan
- Department of Surgery, University of New South Wales, St George HospitalSydney, NSW, Australia
| | - Deborah Black
- School of Public Health and Community Medicine, University of New South WalesSydney, NSW, Australia
| | - Francis C K Chu
- Department of Surgery, University of New South Wales, St George HospitalSydney, NSW, Australia
| | - David L Morris
- Department of Surgery, University of New South Wales, St George HospitalSydney, NSW, Australia
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