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Gao F, Rafiq M, Cong H, Yu B, Shen Y. Current research status and development prospects of embolic microspheres containing biological macromolecules and others. Int J Biol Macromol 2024; 267:131494. [PMID: 38608974 DOI: 10.1016/j.ijbiomac.2024.131494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 03/27/2024] [Accepted: 04/08/2024] [Indexed: 04/14/2024]
Abstract
Transcatheter arterial embolization (TACE) has been used in the treatment of malignant tumors, sudden hemorrhage, uterine fibroids, and other diseases, and with advances in imaging techniques and devices, materials science, and drug release technology, more and more embolic agents that are drug-carrying, self-imaging, or have multiple functions are being developed. Microspheres provide safer and more effective therapeutic results as embolic agents, with their unique spherical appearance and good embolic properties. Embolic microspheres are the key to arterial embolization, blocking blood flow and nutrient supply to the tumor target. This review summarizes some of the currently published embolic microspheres, classifies embolic microspheres according to matrix, and summarizes the characteristics of the microsphere materials, the current status of research, directions, and the value of existing and potential applications. It provides a direction to promote the development of embolic microspheres towards multifunctionalization, and provides a reference to promote the research and application of embolic microspheres in the treatment of tumors.
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Affiliation(s)
- Fengyuan Gao
- College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao 266071, China
| | - Muhammad Rafiq
- College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao 266071, China
| | - Hailin Cong
- College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao 266071, China; State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao 266071, China; School of Materials Science and Engineering, Shandong University of Technology, Zibo 255000, China.
| | - Bing Yu
- College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao 266071, China; State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao 266071, China.
| | - Youqing Shen
- College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao 266071, China; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China
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How Biology Guides the Combination of Locoregional Interventional Therapies and Immunotherapy for Hepatocellular Carcinoma: Cytokines and Their Roles. Cancers (Basel) 2023; 15:cancers15041324. [PMID: 36831664 PMCID: PMC9954096 DOI: 10.3390/cancers15041324] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
As most patients with hepatocellular carcinoma (HCC) are diagnosed at the intermediate or advanced stage and are no longer eligible for curative treatment, the overall survival rate of HCC remains unsatisfactory. Locoregional interventional therapies (LITs), and immune checkpoint inhibitor (ICI)-based immunotherapy, focus on treating HCC, but the efficacy of their individual application is limited. Therefore, the purpose of this review was to discuss the biological roles of cytokines and their therapeutic potential in the combination therapy of LITs and ICI-based immunotherapy. The two common techniques of LITs are ablative and transarterial therapies. Whether LITs are complete or incomplete can largely affect the antitumor immune response and tumor progression. Cytokines that induce both local and systemic responses to LITs, including interferons, interleukins, chemokines, TNF-α, TGF-β, VEGF, and HGF, and their roles are discussed in detail. In addition, specific cytokines that can be used as therapeutic targets to reduce immune-related adverse events (irAEs) are introduced. Overall, incomplete LITs in a tumor, combined with specific cytokines, are thought to be effective at improving the therapeutic efficacy and reducing treatment-induced irAEs, and represent a new hope for managing unresectable HCC.
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Hendriks P, Sudiono DR, Schaapman JJ, Coenraad MJ, Tushuizen ME, Takkenberg RB, Oosterveer TTM, de Geus-Oei LF, van Delden OM, Burgmans MC. Thermal ablation combined with transarterial chemoembolization for hepatocellular carcinoma: What is the right treatment sequence? Eur J Radiol 2021; 144:110006. [PMID: 34717187 DOI: 10.1016/j.ejrad.2021.110006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 10/18/2021] [Accepted: 10/21/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The combination treatment regimen of thermal ablation (TA) and transarterial chemoembolization (TACE) has gained a place in treatment of hepatocellular carcinoma (HCC) lesions > 3 cm unsuitable for surgery. Despite a high heterogeneity in the currently used treatment protocols, the pooled results of combined treatments seem to outperform those of TA or TACE alone. TACE preceding TA has been studied extensively, while results of the reverse treatment sequence are lacking. In this retrospective cohort study we compared the two treatment sequences. PATIENTS AND METHODS 38 patients (median age: 68.5 yrs (range 40-84), male: 34, liver cirrhosis: 33, early stage HCC: 21, intermediate stage HCC: 17) were included in two tertiary referral centers, of whom 27 were treated with TA and adjuvant TACE (TA + TACE). The other 11 patients received TA with neoadjuvant TACE (TACE + TA). Overall survival (OS), time to progression (TTP) and local tumor progression (LTP) free survival were determined for the entire cohort and compared between the two treatment sequences. RESULTS The median OS of all patients was 52.7 months and the median time to LTP was 11.5 months (censored for liver transplantation). No differences were found with respect to OS between the two treatment sequences. Median time to LTP for TACE + TA was 23.6 months and 8.1 months for TA + TACE (p = 0.19). DISCUSSION No statistical differences were found for OS, TTP and time to LTP between patients treated with TA combined with neoadjuvant or adjuvant TACE.
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Affiliation(s)
- P Hendriks
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
| | - D R Sudiono
- Department of Radiology, NWZ Hospital Group, Alkmaar, the Netherlands
| | - J J Schaapman
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - M J Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - M E Tushuizen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - R B Takkenberg
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, the Netherlands
| | - T T M Oosterveer
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
| | - L F de Geus-Oei
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Biomedical Photonic Imaging Group, University of Twente, the Netherlands
| | - O M van Delden
- Department of Radiology, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - M C Burgmans
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
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Dendy MS, Ludwig JM, Stein SM, Kim HS. Locoregional Therapy, Immunotherapy and the Combination in Hepatocellular Carcinoma: Future Directions. Liver Cancer 2019; 8:326-340. [PMID: 31768343 PMCID: PMC6873025 DOI: 10.1159/000494843] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 10/23/2018] [Indexed: 02/04/2023] Open
Abstract
Image-guided locoregional therapies (LRTs) have long been a vital part of treatment regimens for hepatocellular carcinoma (HCC). Ablation, chemoembolization, and radioembolization are examples of commonly used treatment techniques for HCC. This review describes the various methods utilized to treat HCC in the field of interventional oncology and also focuses on new and novel treatment concepts being developed in the field including the use of novel immunotherapy agents and combination therapy of LRTs with immunotherapy.
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Affiliation(s)
- Meaghan S. Dendy
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA
| | - Johannes M. Ludwig
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA,Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Stacey M. Stein
- Division of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA,Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA
| | - Hyun S. Kim
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA,Division of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA,Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA,*Hyun S. Kim, MD, Yale Cancer Center, Yale School of Medicine, 330 Cedar Street, TE 2-224, New Haven, CT 06510 (USA), E-Mail
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Li W, Ni CF. Current status of the combination therapy of transarterial chemoembolization and local ablation for hepatocellular carcinoma. Abdom Radiol (NY) 2019; 44:2268-2275. [PMID: 31016345 DOI: 10.1007/s00261-019-01943-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW To review the current status and ideal time interval of the combination therapy of transarterial chemoembolization (TACE) and local ablation for patients with HCCs. RECENT FINDINGS In recent years, local ablation has been proposed as an alternative curative treatment in the management of HCC. Additionally, many treatment options are available including TACE molecular targeted agents and immune checkpoint inhibitors. Similar overall survival rates and prognoses have been obtained with radiofrequency ablation (RFA) microwave ablation (MWA) and cryoablation for patients with HCCs up to 3 cm in diameter. Yet, MWA has shown superiority in treating large HCCs while cryoablation has several advantages compared with RFA or MWA. Furthermore, the treatment strategy of TACE combined with local ablation is widely accepted by many physicians in order to further increase the survival rate and improve the prognosis of patients with HCCs. However, the time interval between the two sessions of combination therapy remains uncertain in the current guidelines. Combination therapy of TACE and local ablation has advantages on survival and prognosis in patients with HCC compared with monotherapy. Good patient selection for the right modality needs to be carried out to guarantee the most efficacious treatment for HCC patients. Further studies are needed to find the ideal time interval between TACE and local ablation for HCC patients.
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Qiao H, Jia J, Chen W, Di B, Scherman OA, Hu C. Magnetic Regulation of Thermo-Chemotherapy from a Cucurbit[7]uril-Crosslinked Hybrid Hydrogel. Adv Healthc Mater 2019; 8:e1801458. [PMID: 30548830 DOI: 10.1002/adhm.201801458] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Indexed: 12/27/2022]
Abstract
The fabrication, characterization, and therapy efficiency of a noncovalent-bonded hydrogel network, which is assembled by utilizing cucurbit[7]uril as a supramolecular linker to "stick" superparamagnetic γ-Fe2 O3 nanoparticles onto the polymer backbone of catechol-functionalized chitosan are described. The unique barrel-shaped structure of cucurbit[7]uril not only facilitates host-guest recognition with the catechol derivatives, but also forms robust electrostatic interactions between its carbonyl portals and the γ-Fe2 O3 nanoparticles in a supramolecular manner, which leaves the physical and chemical properties of the nanoparticles intact. The γ-Fe2 O3 nanoparticles display vibrational movement and heat generation under an alternating magnetic field, endowing the formed hybrid supramolecular hydrogel with both thermo- and chemotherapy modalities, which are demonstrated both in vitro and in vivo. Here, a facile strategy is introduced to construct noncovalent interactions between a polymer matrix and the incorporated nanoparticles, which is amendable to a wide range of biomedical and industrial applications.
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Affiliation(s)
- Haishi Qiao
- Department of Pharmaceutical EngineeringChina Pharmaceutical University Nanjing 210009 China
| | - Jing Jia
- Key Laboratory of Drug Quality Control and PharmacovigilanceChina Pharmaceutical University Nanjing 210009 China
| | - Wei Chen
- Department of Pharmaceutical EngineeringChina Pharmaceutical University Nanjing 210009 China
| | - Bin Di
- Key Laboratory of Drug Quality Control and PharmacovigilanceChina Pharmaceutical University Nanjing 210009 China
| | - Oren A. Scherman
- Melville Laboratory for Polymer SynthesisDepartment of ChemistryUniversity of Cambridge Cambridge CB2 1EW UK
| | - Chi Hu
- Department of Pharmaceutical EngineeringChina Pharmaceutical University Nanjing 210009 China
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Nazzal M, Gadani S, Said A, Rice M, Okoye O, Taha A, Lentine KL. Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies. GLOBAL SURGERY (LONDON) 2018; 4. [PMID: 29782618 DOI: 10.15761/gos.1000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.
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Affiliation(s)
- Mustafa Nazzal
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Sameer Gadani
- Interventional Radiology, Department of Radiology, St. Louis University Hospital, USA
| | - Abdullah Said
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Mandy Rice
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Obi Okoye
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Ahmad Taha
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Krista L Lentine
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA.,Division of Nephrology, Department of Medicine, St Louis University Hospital, USA
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Yuan W, Yang MJ, Xu J, Yan ZP, Liu R, Qu XD, Wang JH, Qian S. Radiofrequency Ablation Combined With Transarterial Chemoembolization for Specially Located Small Hepatocellular Carcinoma. Technol Cancer Res Treat 2018; 17:1533033818788529. [PMID: 30045673 PMCID: PMC6071156 DOI: 10.1177/1533033818788529] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE To investigate the safety and efficacy of radiofrequency ablation combined with transarterial chemoembolization in patients with specially located small hepatocellular carcinoma. MATERIALS AND METHODS Between March 2014 and March 2017, a total of 26 patients with 26 lesions (10 perivascular, 6 subdiaphragmatic, 5 subcapsular, 5 perivascular, and subdiaphragmatic location; mean diameter 2.12 (0.62) cm), who received radiofrequency ablation-transarterial chemoembolization treatment, were retrospectively analyzed. Local tumor response was assessed by computed tomography/magnetic resonance imaging 1 month after the procedure. Tumor-free survival was also assessed according to the modified Response Evaluation Criteria in Solid Tumors. Complications were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 4.0). RESULTS Complete response was achieved in all patients 1 month after the procedure. During a median follow-up duration of 16.76 months (95% confidence interval: 7.78-25.73 months), local tumor recurrence occurred in 2 patients and new intrahepatic lesions developed in 7 patients. The 1-, 2-, and 3-year cumulative local tumor progression rates were 3.84%, 7.69%, and 7.69%, respectively. The median tumor-free survival duration was 21.96 months (95% confidence interval: 17.58-26.34 months). The 1-, 2-, and 3-year tumor-free survival rates were 67.4%, 46.1%, and 39.3%, respectively. CONCLUSION The radiofrequency ablation-transarterial chemoembolization combination therapy appears to be safe and effective and might be a treatment option for specially located small hepatocellular carcinoma lesions that have a risk of incomplete ablation or major complications.
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Affiliation(s)
- Wei Yuan
- 1 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,2 Shanghai Institution of Medical Imaging, Shanghai, China
| | - Min-Jie Yang
- 1 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,2 Shanghai Institution of Medical Imaging, Shanghai, China
| | - Jiang Xu
- 3 Department of Rehabilitation, Huai'an Second People's Hospital, The Affiliated Hospital of Xuzhou Medical University, Huai'an, China
| | - Zhi-Ping Yan
- 1 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,2 Shanghai Institution of Medical Imaging, Shanghai, China
| | - Rong Liu
- 1 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,2 Shanghai Institution of Medical Imaging, Shanghai, China
| | - Xu-Dong Qu
- 1 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,2 Shanghai Institution of Medical Imaging, Shanghai, China
| | - Jian-Hua Wang
- 1 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,2 Shanghai Institution of Medical Imaging, Shanghai, China
| | - Sheng Qian
- 1 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,2 Shanghai Institution of Medical Imaging, Shanghai, China
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Efficacy and safety of combination therapy of chemoembolization and radiofrequency ablation with different time intervals for hepatocellular carcinoma patients. Surg Oncol 2017; 26:236-241. [DOI: 10.1016/j.suronc.2017.04.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 04/28/2017] [Accepted: 04/30/2017] [Indexed: 01/13/2023]
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Crocetti L, Bargellini I, Cioni R. Loco-regional treatment of HCC: current status. Clin Radiol 2017; 72:626-635. [PMID: 28258743 DOI: 10.1016/j.crad.2017.01.013] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 01/18/2017] [Accepted: 01/25/2017] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) represents one of the few cancers for which locoregional treatments are recognised as being able to cure and/or prolong survival and are included in international guidelines. This is due to the unique nature of HCC, in most cases occurring in patients with underlying virus- or alcohol-related cirrhosis. The treatment choice in patients with HCC is therefore driven not only by tumour staging, as in the great majority of cancers, but also by careful evaluation of liver function and physical status. Another specific feature of HCC is that it is the only tumour that can be cured by organ transplantation, with the aim of treating both the cancer and underlying liver disease. These characteristics configure a complex scenario and prompt the need for close cooperation among interventional oncologists, surgeons, hepatologists, and anaesthesiologists. In patients with limited hepatic disease, preserved hepatic function and good performance status, categorised as very early and early-stage HCC according to the Barcelona Clinic Liver Cancer (BCLC) classification, image-guided tumour ablation is included among the curative treatments. More than half of patients with HCC are, however, diagnosed late, despite the widespread implementation of surveillance programmes, when curative treatments cannot be applied. For patients presenting with multinodular HCC and relatively preserved liver function, absence of cancer-related symptoms, and no evidence of vascular invasion or extrahepatic spread transcatheter arterial chemoembolisation (TACE) is the current standard of care. Although anti-tumour activity and promising survival results has been reported in cohorts of patients with advanced HCC treated with radio-embolisation, systemic treatment with the multi-kinase inhibitor, sorafenib, is still recommended for patients at this stage. In this article, current treatment strategies for HCC according to tumour stage are discussed, underlining the latest advances in the literature and technical developments.
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Affiliation(s)
- L Crocetti
- Division of Interventional Radiology, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Cisanello University Hospital, Pisa, Italy.
| | - I Bargellini
- Division of Interventional Radiology, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Cisanello University Hospital, Pisa, Italy
| | - R Cioni
- Division of Interventional Radiology, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Cisanello University Hospital, Pisa, Italy
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Abdelsalam ME, Murthy R, Avritscher R, Mahvash A, Wallace MJ, Kaseb AO, Odisio BC. Minimally invasive image-guided therapies for hepatocellular carcinoma. J Hepatocell Carcinoma 2016; 3:55-61. [PMID: 27785450 PMCID: PMC5067062 DOI: 10.2147/jhc.s92732] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic liver disease, which affects management decisions. Image-guided percutaneous ablative or transarterial therapies have acquired wide acceptance in HCC management as a single treatment modality or combined with other treatment options in patients who are not amenable for surgery. Recently, such treatment modalities have also been used for bridging or downsizing before definitive treatment (ie, surgical resection or liver transplantation). This review focuses on the use of minimally invasive image-guided locoregional therapies for HCC. Additionally, it highlights recent advancements in imaging and catheter technology, embolic materials, chemotherapeutic agents, and delivery techniques; all lead to improved patient outcomes, thereby increasing the interest in these invasive techniques.
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Affiliation(s)
| | | | | | | | | | - Ahmed O Kaseb
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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12
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Carrilho FJ, Mattos AAD, Vianey AF, Vezozzo DCP, Marinho F, Souto FJ, Cotrim HP, Coelho HSM, Silva I, Garcia JHP, Kikuchi L, Lofego P, Andraus W, Strauss E, Silva G, Altikes I, Medeiros JE, Bittencourt PL, Parise ER. Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma. ARQUIVOS DE GASTROENTEROLOGIA 2016; 52 Suppl 1:2-14. [PMID: 26959803 DOI: 10.1590/s0004-28032015000500001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology.
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Affiliation(s)
| | | | | | | | - Fábio Marinho
- Hospital Português de Beneficiência, Recife, PE, Brazil
| | | | | | | | - Ivonete Silva
- Faculdade de Medicina, Universidade Federal de São Paulo, SP, Brazil
| | | | - Luciana Kikuchi
- Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Patricia Lofego
- Faculdade de Medicina, Universidade Federal do Espírito Santo, ES, Brazil
| | | | - Edna Strauss
- Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | | | | | | | | | - Edison R Parise
- Faculdade de Medicina, Universidade Federal de São Paulo, SP, Brazil
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Lencioni R, Cioni D. RFA plus lyso-thermosensitive liposomal doxorubicin: in search of the optimal approach to cure intermediate-size hepatocellular carcinoma. Hepat Oncol 2016; 3:193-200. [PMID: 30191041 DOI: 10.2217/hep-2016-0005] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Accepted: 05/10/2016] [Indexed: 01/10/2023] Open
Abstract
When heated during a radiofrequency ablation (RFA) procedure to ≥40°C, lyso-thermosensitive liposomal doxorubicin (LTLD) produces high drug concentration in the surrounding margins of the ablation zone. The hypothesis that the RFA + LTLD combination can effectively treat hepatocellular carcinoma (HCC) was investigated in the HEAT study: adding LTLD did not improve the efficacy of normal practice RFA. However, among the 285 patients with a solitary lesion who received at least 45-min RFA dwell time, the hazard ratio for overall survival was 0.63 (95% CI: 0.41-0.96; p = 0.04). The OPTIMA study is currently ongoing to test the hypothesis that adding LTLD to a standardized RFA lasting ≥45 min increases survival compared with standardized RFA alone.
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Affiliation(s)
- Riccardo Lencioni
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Dania Cioni
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
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Bruix J, Reig M, Sherman M. Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma. Gastroenterology 2016; 150:835-53. [PMID: 26795574 DOI: 10.1053/j.gastro.2015.12.041] [Citation(s) in RCA: 1264] [Impact Index Per Article: 140.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 12/09/2015] [Accepted: 12/16/2015] [Indexed: 02/07/2023]
Abstract
Evidence-based management of patients with hepatocellular carcinoma (HCC) is key to their optimal care. For individuals at risk for HCC, surveillance usually involves ultrasonography (there is controversy over use of biomarkers). A diagnosis of HCC is made based on findings from biopsy or imaging analyses. Molecular markers are not used in diagnosis or determination of prognosis and treatment for patients. The Barcelona Clinic Liver Cancer algorithm is the most widely used staging system. Patients with single liver tumors or as many as 3 nodules ≤3 cm are classified as having very early or early-stage cancer and benefit from resection, transplantation, or ablation. Those with a greater tumor burden, confined to the liver, and who are free of symptoms are considered to have intermediate-stage cancer and can benefit from chemoembolization if they still have preserved liver function. Those with symptoms of HCC and/or vascular invasion and/or extrahepatic cancer are considered to have advanced-stage cancer and could benefit from treatment with the kinase inhibitor sorafenib. Patients with end-stage HCC have advanced liver disease that is not suitable for transplantation and/or have intense symptoms. Studies now aim to identify molecular markers and imaging techniques that can detect patients with HCC at earlier stages and better predict their survival time and response to treatment.
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Affiliation(s)
- Jordi Bruix
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
| | - Maria Reig
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Morris Sherman
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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15
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Forner A, Reig M, Varela M, Burrel M, Feliu J, Briceño J, Sastre J, Martí-Bonmati L, Llovet JM, Bilbao JI, Sangro B, Pardo F, Ayuso C, Bru C, Tabernero J, Bruix J. [Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH]. Med Clin (Barc) 2016; 146:511.e1-511.e22. [PMID: 26971984 DOI: 10.1016/j.medcli.2016.01.028] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 01/22/2016] [Accepted: 01/28/2016] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.
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Affiliation(s)
- Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Oviedo, España
| | - Marta Burrel
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Jaime Feliu
- Servicio de Oncología Médica, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Sociedad Española de Oncología Médica, Madrid, España
| | - Javier Briceño
- Unidad de Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Javier Sastre
- Servicio de Oncología Médica, Hospital Clínico San Carlos, Madrid, España
| | - Luis Martí-Bonmati
- Departamento de Radiología, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - Josep María Llovet
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Mount Sinai Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, Estados Unidos
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Unidad de Hepatología, Departamento de Medicina Interna, Clínica Universidad de Navarra, Pamplona, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Carmen Ayuso
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Concepció Bru
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebrón, Barcelona, Universidad Autónoma de Barcelona, Barcelona, España
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España.
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Mauer K, O'Kelley R, Podda N, Flanagan S, Gadani S. New treatment modalities for hepatocellular cancer. Curr Gastroenterol Rep 2015; 17:442. [PMID: 25869473 DOI: 10.1007/s11894-015-0442-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Heptatocellular (HCC) is a rapidly progressive fatal malignancy often presenting at an advanced stage at the time of initial diagnosis. Loco-regional therapies for early-stage HCC including surgical options (surgical resection and liver transplant) and percutaneous ablations could be potentially curative. Recent technological advances in percutaneous image-guided ablations have provided clinicians with a range of options which have proven to be equal to or better than surgical resection. For intermediate- and advanced-stage HCC, palliative therapies are available which significantly increase overall and progression-free survival. These palliative therapies include intra-arterial chemo- or radioembolization as monotherapy or in combination with percutaneous ablation or antiangiogenic drugs. Availability of a multitude of treatment options for various stages of HCC as well as conflicting data comparing their safety and efficacy presented in the several randomized controlled trials poses a significant challenge to hepatologists, surgeons, and interventional radiologists in selecting optimal therapy for their patients. The aim of this article is to review and discuss currently available therapies at each stage of HCC along with presenting clinical data published in most recent and relevant randomized controlled trials.
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Affiliation(s)
- Kurt Mauer
- Division of Interventional Radiology, Department of Radiology, Saint Louis University School of Medicine, 3635 Vista Ave at Grand Blvd, St Louis, MO, 63110, USA,
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17
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Wells SA, Hinshaw JL, Lubner MG, Ziemlewicz TJ, Brace CL, Lee FT. Liver Ablation: Best Practice. Radiol Clin North Am 2015; 53:933-71. [PMID: 26321447 DOI: 10.1016/j.rcl.2015.05.012] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Tumor ablation in the liver has evolved to become a well-accepted tool in the management of increasing complex oncologic patients. At present, percutaneous ablation is considered first-line therapy for very early and early hepatocellular carcinoma and second-line therapy for colorectal carcinoma liver metastasis. Because thermal ablation is a treatment option for other primary and secondary liver tumors, an understanding of the underlying tumor biology is important when weighing the potential benefits of ablation. This article reviews ablation modalities, indications, patient selection, and imaging surveillance, and emphasizes technique-specific considerations for the performance of percutaneous ablation.
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Affiliation(s)
- Shane A Wells
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA.
| | - J Louis Hinshaw
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
| | - Meghan G Lubner
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
| | - Timothy J Ziemlewicz
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
| | - Christopher L Brace
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA; Department of Biomedical Engineering, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
| | - Fred T Lee
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA; Department of Biomedical Engineering, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
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Kalra N, Gupta P, Chawla Y, Khandelwal N. Locoregional treatment for hepatocellular carcinoma: The best is yet to come. World J Radiol 2015; 7:306-18. [PMID: 26516427 PMCID: PMC4620111 DOI: 10.4329/wjr.v7.i10.306] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 09/06/2015] [Accepted: 10/01/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth-most common type of cancer worldwide. The only definitive treatment modalities capable of achieving a cure are hepatic resection and hepatic transplantation. However, most patients are not candidates for these therapies. Overall, treatment options are driven by the stage of HCC. Early-stage disease is treated with ablative therapies, with radiofrequency ablation the ablative therapy of choice. Microwave ablation and irreversible electroporation are the other upcoming alternatives. Intermediate-stage disease is managed with transarterial chemoembolization (TACE), while advanced-stage disease is managed by sorafenib, with TACE and radioembolization as other alternatives.
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Yang W. Current status and prospective of imaging guided radiofrequency ablation in medium to large sized hepatocellular carcinomas. Shijie Huaren Xiaohua Zazhi 2015; 23:4771-4777. [DOI: 10.11569/wcjd.v23.i30.4771] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The incidence of liver cancer is high in China and effective treatments are required. Recently, imaging guided radiofrequency ablation (RFA) has become increasingly accepted in treating solid tumors because of minimal invasiveness, easy operation and effectiveness. The outcome of RFA in small liver tumors is even comparable to that of surgery. However, the RFA efficacy in larger ( > 3.0 cm) liver tumors is not satisfactory and recurrence after treatment is common. The development of basic research and RFA device has provided more opportunities for us to treat>3.0 cm liver tumors. The successful ablation of solid tumors relies on three key components, the technology (i.e., the RFA generator and electrodes selected), the biology of the tumor and background tissue, and operator factors. The current development and prospective of the three main elements will be the focus in this review.
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Liu YS, Lin XZ, Tsai HM, Tsai HW, Chen GC, Chen SF, Kang JW, Chou CM, Chen CY. Development of biodegradable radiopaque microsphere for arterial embolization-a pig study. World J Radiol 2015; 7:212-219. [PMID: 26339465 PMCID: PMC4553253 DOI: 10.4329/wjr.v7.i8.212] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Revised: 07/07/2015] [Accepted: 08/03/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To develop a new type of calibrated, biodegradable, and imaging detectable microsphere and evaluated its embolization safety and efficacy on pig’s liver and spleen.
METHODS: Six kinds of pharmaceutical excipient were combined and atomized to form our microsphere. Twenty-four male Lanyu pigs weighing 25-30 kg were used. The arteries of spleen and liver were embolized with Gelfoam, Embosphere, or our microsphere. The serum biochemical tests, computed tomography (CT), liver perfusion scan, and tissue microscopy examination were done to evaluate the safety and efficacy of embolization.
RESULTS: Radiopaque microspheres with a size ranging from 300 to 400 μm were produced. Embolization of hepatic and splenic artery of pigs with our microsphere significantly reduced the blood flow of liver and resulted in splenic infarction. The follow-up CT imaging and the microscopic examination showed intraarterial degradation of Gelfoam and microsphere. The blood tests demonstrated insignificant changes with regards to liver and renal functions.
CONCLUSION: Our microspheres, with the unique characteristics, can be used for transcatheter arterial embolization with effects equivalent to or better than Gelfoam and Embosphere in pigs.
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Bruix J, Han KH, Gores G, Llovet JM, Mazzaferro V. Liver cancer: Approaching a personalized care. J Hepatol 2015; 62:S144-56. [PMID: 25920083 PMCID: PMC4520430 DOI: 10.1016/j.jhep.2015.02.007] [Citation(s) in RCA: 228] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Revised: 02/03/2015] [Accepted: 02/04/2015] [Indexed: 12/04/2022]
Abstract
The knowledge and understanding of all aspects of liver cancer [this including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA)] have experienced a major improvement in the last decades. New laboratory technologies have identified several molecular abnormalities that, at the very end, should provide an accurate stratification and optimal treatment of patients diagnosed with liver cancer. The seminal discovery of the TP53 hotspot mutation [1 ,2 ] was an initial landmark step for the future classification and treatment decision using conventional clinical criteria blended with molecular data. At the same time, the development of ultrasound, computed tomography (CT) and magnetic resonance (MR) has been instrumental for earlier diagnosis, accurate staging and treatment advances. Several treatment options with proven survival benefit if properly applied are now available. Major highlights include: i) acceptance of liver transplantation for HCC if within the Milan criteria [3 ], ii) recognition of ablation as a potentially curative option [4 ,5 ], iii) proof of benefit of chemoembolization (TACE), [6 ] and iv) incorporation of sorafenib as an effective systemic therapy [7 ]. These options are part of the widely endorsed BCLC staging and treatment model (Fig. 1 ) [8 ,9 ]. This is clinically useful and it will certainly keep evolving to accommodate new scientific evidence. This review summarises the data which are the basis for the current recommendations for clinical practice, while simultaneously exposes the areas where more research is needed to fulfil the still unmet needs (Table 1 ).
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Affiliation(s)
- Jordi Bruix
- Barcelona Clinic Liver Cancer Group (BCLC), Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Universitat de Barcelona, Catalonia, Spain.
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Gregory Gores
- Mayo Clinic, Mayo College of Medicine, Rochester, MN, USA
| | - Josep Maria Llovet
- Barcelona Clinic Liver Cancer Group (BCLC), Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Universitat de Barcelona, Catalonia, Spain; Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
| | - Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation, Istituto Nazionale Tumori IRCCS (National Cancer Institute), Milan 20133, Italy
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23
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Abstract
Image-guided ablation (IGA) techniques have evolved considerably over the past 20 years and are increasingly used to definitively treat small primary cancers of the liver and kidney. IGA is recommended by most guidelines as the best therapeutic choice for patients with early stage hepatocellular carcinoma (HCC)-defined as either a single tumour smaller than 5 cm or up to three nodules smaller than 3 cm-when surgical options are precluded, and has potential as first-line therapy, in lieu of surgery, for patients with very early stage tumours smaller than 2 cm. With regard to renal cell carcinoma, despite the absence of any randomized trial comparing the outcomes of IGA with those of standard partial nephrectomy, a growing amount of data demonstrate robust oncological outcomes for this minimally invasive approach and testify to its potential as a standard-of-care treatment. Herein, we review the various ablation techniques, the supporting evidence, and clinical application of IGA in the treatment of primary liver and kidney cancers.
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Affiliation(s)
- David J Breen
- Department of Radiology, University Hospitals of Southampton, Tremona Road, Southampton, Hampshire SO16 6YD, UK
| | - Riccardo Lencioni
- Department of Liver Transplantation, Hepatology and Infectious Diseases, Division of Diagnostic Imaging and Intervention, Pisa University Hospital and School of Medicine, Building No. 29, 2nd Floor, Via Paradisa 2, IT-56124 Pisa, Italy
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Duan X, Zhou G, Han X, Ren J, Zheng C, Liang H, Feng G. Radiofrequency ablation combined with transcatheter therapy in rabbit VX2 liver tumors: effects and histopathological characteristics. Acta Radiol 2015; 56:87-96. [PMID: 24425792 DOI: 10.1177/0284185113520266] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) treatment (TACE-RFA) has been confirmed superior to TACE or RFA alone in animal liver tumors. TACE before RFA was shown to increase hepatocellular damage. Further optimization of the combination strategy for transcatheter arterial embolization (TAE) or TACE combined with RFA is warranted. PURPOSE To determine the optimal strategy for radiofrequency ablation combined with transcatheter therapies in VX2 liver tumors in a rabbit model. MATERIAL AND METHODS Twenty-four Japanese White rabbits with VX2 liver tumors were randomly divided into four groups: TACE-RFA (TACE-RFA group), transcatheter arterial embolization (TAE) combined with RFA treatment (TAE-RFA group), RFA only group, and TACE only group. Blood samples were collected 1 day before the operation and at 3 and 7 days postoperatively. Seven days after the operation, maximal diameters of coagulation or infarcted zones in the gross specimens, CT images, histopathological characteristics, tumor necrotic rate, and growth rate were compared. RESULTS Significantly larger mean long-axis (P < 0.05) and short-axis (P < 0.05) diameters of coagulation and infarction were observed in the TACE-RFA group compared with the TAE-RFA, RFA, and TACE groups on day 7; and the TAE-RFA group showed a significant (P < 0.05) increase versus the RFA and TACE groups on day 7. There were no significant differences in tumor growth rate (109.3 ± 37.5 vs. 119.0 ± 43.1%, P = 0.45) and necrotic rate (89.5 ± 12.0 vs. 83.5 ± 9.3%, P = 0.73) between the TACE-RFA and TAE-RFA groups. TACE-RFA was more effective for achieving tumor destruction than the other treatment strategies, but led to increased rabbits discomfort and more severe liver dysfunction compared with TAE-RFA. CONCLUSION TAE-RFA appears to be a beneficial therapeutic modality for treating VX2 liver tumors in a rabbit model.
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Affiliation(s)
- XuHua Duan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China
| | - GuoFeng Zhou
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - XinWei Han
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China
| | - JianZhuang Ren
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China
| | - ChuanSheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - HuiMin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - GanSheng Feng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
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Zhou W, Jiang Y, Chen L, Ling L, Liang M, Pan H, Wang S, Ding Q, Liu X, Wang S. Image and pathological changes after microwave ablation of breast cancer: A pilot study. Eur J Radiol 2014; 83:1771-7. [DOI: 10.1016/j.ejrad.2014.06.015] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Revised: 06/14/2014] [Accepted: 06/20/2014] [Indexed: 11/29/2022]
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Berliner L, Lemke HU, vanSonnenberg E, Ashamalla H, Mattes MD, Dosik D, Hazin H, Shah S, Mohanty S, Verma S, Esposito G, Bargellini I, Battaglia V, Caramella D, Bartolozzi C, Morrison P. Model-guided therapy for hepatocellular carcinoma: a role for information technology in predictive, preventive and personalized medicine. EPMA J 2014; 5:16. [PMID: 25538797 PMCID: PMC4274760 DOI: 10.1186/1878-5085-5-16] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 08/07/2014] [Indexed: 12/18/2022]
Abstract
Predictive, preventive and personalized medicine (PPPM) may have the potential to eventually improve the nature of health care delivery. However, the tools required for a practical and comprehensive form of PPPM that is capable of handling the vast amounts of medical information that is currently available are currently lacking. This article reviews a rationale and method for combining and integrating diagnostic and therapeutic management with information technology (IT), in a manner that supports patients through their continuum of care. It is imperative that any program devised to explore and develop personalized health care delivery must be firmly rooted in clinically confirmed and accepted principles and technologies. Therefore, a use case, relating to hepatocellular carcinoma (HCC), was developed. The approach to the management of medical information we have taken is based on model theory and seeks to implement a form of model-guided therapy (MGT) that can be used as a decision support system in the treatment of patients with HCC. The IT structures to be utilized in MGT include a therapy imaging and model management system (TIMMS) and a digital patient model (DPM). The system that we propose will utilize patient modeling techniques to generate valid DPMs (which factor in age, physiologic condition, disease and co-morbidities, genetics, biomarkers and responses to previous treatments). We may, then, be able to develop a statistically valid methodology, on an individual basis, to predict certain diseases or conditions, to predict certain treatment outcomes, to prevent certain diseases or complications and to develop treatment regimens that are personalized for that particular patient. An IT system for predictive, preventive and personalized medicine (ITS-PM) for HCC is presented to provide a comprehensive system to provide unified access to general medical and patient-specific information for medical researchers and health care providers from different disciplines including hepatologists, gastroenterologists, medical and surgical oncologists, liver transplant teams, interventional radiologists and radiation oncologists. The article concludes with a review providing an outlook and recommendations for the application of MGT to enhance the medical management of HCC through PPPM.
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Affiliation(s)
- Leonard Berliner
- New York Methodist Hospital, Brooklyn, NY 11215, USA
- Weill Medical College of Cornell University, New York, NY 10021, USA
| | - Heinz U Lemke
- Technical University of Berlin, 10623 Berlin, Germany
- University of Southern California, Los Angeles, CA, 90089, USA
| | - Eric vanSonnenberg
- David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
- University of Arizona College of Medicine, Tucson, AZ, 85724, USA
| | - Hani Ashamalla
- New York Methodist Hospital, Brooklyn, NY 11215, USA
- Weill Medical College of Cornell University, New York, NY 10021, USA
| | | | - David Dosik
- New York Methodist Hospital, Brooklyn, NY 11215, USA
- Weill Medical College of Cornell University, New York, NY 10021, USA
| | - Hesham Hazin
- New York Methodist Hospital, Brooklyn, NY 11215, USA
| | - Syed Shah
- New York Methodist Hospital, Brooklyn, NY 11215, USA
- Weill Medical College of Cornell University, New York, NY 10021, USA
| | - Smruti Mohanty
- New York Methodist Hospital, Brooklyn, NY 11215, USA
- Weill Medical College of Cornell University, New York, NY 10021, USA
| | - Sid Verma
- New York Methodist Hospital, Brooklyn, NY 11215, USA
| | | | - Irene Bargellini
- University Hospital Pisa, University of Pisa (I), 56126 Pisa, Italy
| | | | - Davide Caramella
- University Hospital Pisa, University of Pisa (I), 56126 Pisa, Italy
| | - Carlo Bartolozzi
- University Hospital Pisa, University of Pisa (I), 56126 Pisa, Italy
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Forner A, Gilabert M, Bruix J, Raoul JL. Treatment of intermediate-stage hepatocellular carcinoma. Nat Rev Clin Oncol 2014; 11:525-35. [PMID: 25091611 DOI: 10.1038/nrclinonc.2014.122] [Citation(s) in RCA: 343] [Impact Index Per Article: 31.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC)-closely associated with liver cirrhosis and, in fact, the main cause of death in patients with such disease-is now recognized as one of the most-prevalent and lethal neoplasms worldwide. Prognosis and allocation of the multiple available treatment options for patients with HCC are influenced not only by tumour stage, but also by the degree of liver-function impairment. Therefore, accurate assessment and classification of disease is important for patient management. According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, intermediate-stage HCC is defined as extensive multifocal disease without vascular invasion in patients with preserved liver function and absence of cancer-related symptoms; in this context, transarterial chemoembolization (TACE) is considered the standard treatment. The use of drug-eluting beads has enabled standardization of this procedure, resulting in higher reproducibility and tolerability of the treatment. Nevertheless, not all patients with intermediate-stage HCC are good candidates for TACE and, for such patients in whom TACE is not appropriate or has failed, other treatments can be considered, including sorafenib. Radioembolization is a promising alternative that deserves further prospective studies. Herein, we review the current approaches used to accurately stratify patients with intermediate-stage HCC and subsequently allocate the most-appropriate treatments. The key developments in therapeutic strategies are also discussed.
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Affiliation(s)
- Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Centre for Biomedical Research Network for Hepatic and Digestive Diseases, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain
| | - Marine Gilabert
- Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Centre for Biomedical Research Network for Hepatic and Digestive Diseases, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain
| | - Jean-Luc Raoul
- Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France
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28
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Forner A, Gilabert M, Bruix J, Raoul JL. Treatment of intermediate-stage hepatocellular carcinoma. Nat Rev Clin Oncol 2014. [PMID: 25091611 DOI: 10.1038/nrclinonc.2014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC)-closely associated with liver cirrhosis and, in fact, the main cause of death in patients with such disease-is now recognized as one of the most-prevalent and lethal neoplasms worldwide. Prognosis and allocation of the multiple available treatment options for patients with HCC are influenced not only by tumour stage, but also by the degree of liver-function impairment. Therefore, accurate assessment and classification of disease is important for patient management. According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, intermediate-stage HCC is defined as extensive multifocal disease without vascular invasion in patients with preserved liver function and absence of cancer-related symptoms; in this context, transarterial chemoembolization (TACE) is considered the standard treatment. The use of drug-eluting beads has enabled standardization of this procedure, resulting in higher reproducibility and tolerability of the treatment. Nevertheless, not all patients with intermediate-stage HCC are good candidates for TACE and, for such patients in whom TACE is not appropriate or has failed, other treatments can be considered, including sorafenib. Radioembolization is a promising alternative that deserves further prospective studies. Herein, we review the current approaches used to accurately stratify patients with intermediate-stage HCC and subsequently allocate the most-appropriate treatments. The key developments in therapeutic strategies are also discussed.
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Affiliation(s)
- Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Centre for Biomedical Research Network for Hepatic and Digestive Diseases, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain
| | - Marine Gilabert
- Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Centre for Biomedical Research Network for Hepatic and Digestive Diseases, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain
| | - Jean-Luc Raoul
- Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France
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Transcatheter CT Arterial Portography and CT Hepatic Arteriography for Liver Tumor Visualization during Percutaneous Ablation. J Vasc Interv Radiol 2014; 25:1101-1111.e4. [DOI: 10.1016/j.jvir.2014.02.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Revised: 01/31/2014] [Accepted: 02/03/2014] [Indexed: 12/24/2022] Open
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Malagari K, Emmanouil E, Pomoni M, Kelekis D. Chemoembolization with DC Bead™ for the treatment of hepatocellular carcinoma: an update. Hepat Oncol 2014; 1:205-214. [PMID: 30190955 DOI: 10.2217/hep.13.18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
In this review, DC Bead™ for the treatment of hepatocellular carcinoma is discussed. The embolic device and its mechanism of action is described, focusing on the clinical application and the preclinical background. Guidelines for patient selection and management, along with technical considerations for the appropriate use are provided. Clinical details including local response, comparison with conventional chemoembolization and bland embolization, survival and safety issues are also discussed in detail.
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Affiliation(s)
- Katerina Malagari
- 2nd Department of Radiology University of Athens, Medical School, 19 Monis Kyccou, 15 669 Papagou, Athens, Greece
| | - Emmanouil Emmanouil
- 2nd Department of Radiology University of Athens, Medical School, 19 Monis Kyccou, 15 669 Papagou, Athens, Greece
| | - Maria Pomoni
- 2nd Department of Radiology University of Athens, Medical School, 19 Monis Kyccou, 15 669 Papagou, Athens, Greece
| | - Dimitrios Kelekis
- 2nd Department of Radiology University of Athens, Medical School, 19 Monis Kyccou, 15 669 Papagou, Athens, Greece
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Seror O, N'Kontchou G, Van Nhieu JT, Rabahi Y, Nahon P, Laurent A, Trinchet JC, Cherqui D, Vicaut E, Beaugrand M, Sellier N. Histopathologic comparison of monopolar versus no-touch multipolar radiofrequency ablation to treat hepatocellular carcinoma within Milan criteria. J Vasc Interv Radiol 2014; 25:599-607. [PMID: 24529547 DOI: 10.1016/j.jvir.2013.11.025] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2013] [Revised: 11/20/2013] [Accepted: 11/22/2013] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To compare histopathologically the completeness of radiofrequency (RF) ablation to treat hepatocellular carcinoma (HCC) with monopolar or multipolar technique. MATERIALS AND METHODS Thirty-five consecutive patients (mean age, 59 y) with cirrhosis and HCC (n = 59) within Milan criteria received RF ablation and subsequently underwent liver transplantation (LT) for tumor progression or liver failure. Data were extracted retrospectively from a prospective database. Thirty nodules were treated with a monopolar device with internally cooled (n = 17) or perfused (n = 13) electrodes, and 29 were treated with a multipolar technique with internally cooled electrodes based on the "no-touch" concept. This consisted of inserting two or three straight electrodes around the nodule to avoid intratumor puncture to the greatest extent possible. Effectiveness of the three devices was compared by histopathologic examination of explants. Fisher exact and χ(2) tests and multivariate logistic regression analysis were performed. RESULTS Mean sizes of nodules ablated (25, 22, and 21.6 mm) and median times from ablation to LT (11, 7.5, and 8.4 months) for patients treated with the monopolar internally cooled electrode device (MoICD), monopolar perfused electrode device (MoPED), and multipolar internally cooled electrode device (MuICD), respectively, were similar (P = .8 and P = .9, respectively). Pathologic examination showed complete necrosis for eight of 17 and six of 13 nodules treated with the MoICD and MoPED, respectively, versus 26 of 29 treated with the MuICD (P = .0019). In multivariate analysis, RF technique remained the predictive factor for complete necrosis (P = .005). CONCLUSIONS Ablation of small HCCs with multipolar RF ablation based on the no-touch concept improves the rate of complete necrosis during pathologic examination compared with monopolar techniques.
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Affiliation(s)
- Olivier Seror
- Radiology Service (O.S., Y.R., N.S.); Formation and Research Unit of Health, Medicine and Human Biology (O.S., Y.R., P.N., J.C.T., M.B., N.S.), Sorbonne Paris Cité, Université Paris 13, Bobigny.
| | - Gisèle N'Kontchou
- Hepatogastroenterology Service (G.N., P.N., J.C.T., M.B.), Assistance-Publique Hôpitaux de Paris, Hôpitaux Universitaires Paris Saint-Denis, Centre Hospitalo-Universitaire Jean Verdier, Bondy
| | | | - Yacine Rabahi
- Radiology Service (O.S., Y.R., N.S.); Formation and Research Unit of Health, Medicine and Human Biology (O.S., Y.R., P.N., J.C.T., M.B., N.S.), Sorbonne Paris Cité, Université Paris 13, Bobigny
| | - Pierre Nahon
- Hepatogastroenterology Service (G.N., P.N., J.C.T., M.B.), Assistance-Publique Hôpitaux de Paris, Hôpitaux Universitaires Paris Saint-Denis, Centre Hospitalo-Universitaire Jean Verdier, Bondy; Formation and Research Unit of Health, Medicine and Human Biology (O.S., Y.R., P.N., J.C.T., M.B., N.S.), Sorbonne Paris Cité, Université Paris 13, Bobigny
| | - Alexis Laurent
- Visceral Surgery Service (A.L., D.C.), Assistance-Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Centre Hospitalo-Universitaire Henri Mondor, Créteil
| | - Jean Claude Trinchet
- Hepatogastroenterology Service (G.N., P.N., J.C.T., M.B.), Assistance-Publique Hôpitaux de Paris, Hôpitaux Universitaires Paris Saint-Denis, Centre Hospitalo-Universitaire Jean Verdier, Bondy; Formation and Research Unit of Health, Medicine and Human Biology (O.S., Y.R., P.N., J.C.T., M.B., N.S.), Sorbonne Paris Cité, Université Paris 13, Bobigny
| | - Daniel Cherqui
- Visceral Surgery Service (A.L., D.C.), Assistance-Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Centre Hospitalo-Universitaire Henri Mondor, Créteil
| | - Eric Vicaut
- Department of Clinical Research (E.V.), Assistance-Publique Hôpitaux de Paris, Groupe Hospitalo-Universitaire Saint Louis-Lariboisière-Fernand Widal, Hôpital Fernand Widal, Paris, France
| | - Michel Beaugrand
- Hepatogastroenterology Service (G.N., P.N., J.C.T., M.B.), Assistance-Publique Hôpitaux de Paris, Hôpitaux Universitaires Paris Saint-Denis, Centre Hospitalo-Universitaire Jean Verdier, Bondy; Formation and Research Unit of Health, Medicine and Human Biology (O.S., Y.R., P.N., J.C.T., M.B., N.S.), Sorbonne Paris Cité, Université Paris 13, Bobigny
| | - Nicolas Sellier
- Radiology Service (O.S., Y.R., N.S.); Formation and Research Unit of Health, Medicine and Human Biology (O.S., Y.R., P.N., J.C.T., M.B., N.S.), Sorbonne Paris Cité, Université Paris 13, Bobigny
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Brennan IM, Ahmed M. Imaging features following transarterial chemoembolization and radiofrequency ablation of hepatocellular carcinoma. Semin Ultrasound CT MR 2014; 34:336-51. [PMID: 23895906 DOI: 10.1053/j.sult.2013.04.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Transarterial chemoembolization and radiofrequency ablation are currently the most widely used modalities in the minimally invasive treatment of unresectable hepatocellular carcinoma. This article briefly summarizes the minimally invasive therapeutic options in the management of hepatocellular carcinoma focusing on transarterial chemoembolization and radiofrequency ablation and describes normal post-treatment imaging appearances. Imaging features of post-treatment local tumor recurrence as well as procedure-related complications following these interventions have also been described.
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Affiliation(s)
- Ian M Brennan
- Section of Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA 02215, USA.
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Radiofrequency Ablation After Arterial Injection of Miriplatin–Iodized Oil Suspension Into Swine Liver: Ablative Zone Size and Tissue Platinum Concentration. Cardiovasc Intervent Radiol 2013; 37:1047-52. [DOI: 10.1007/s00270-013-0779-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Accepted: 10/10/2013] [Indexed: 12/16/2022]
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Salem R, Lewandowski RJ. Chemoembolization and radioembolization for hepatocellular carcinoma. Clin Gastroenterol Hepatol 2013; 11:604-11; quiz e43-4. [PMID: 23357493 PMCID: PMC3800021 DOI: 10.1016/j.cgh.2012.12.039] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2012] [Revised: 12/19/2012] [Accepted: 12/21/2012] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) continues to represent a major worldwide problem. Although treatments such as resection, transplantation, and ablation may provide a chance for a cure, these options are often precluded because of advanced disease presentation. Palliative treatments include transarterial embolization and systemic therapies. This review will summarize the state of the science for embolic therapies in HCC (conventional and drug-eluting chemoembolization, radioembolization) as well as discuss related topics including HCC staging, assessment of response, and ongoing clinical trials.
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Affiliation(s)
- Riad Salem
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA.
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Bargellini I, Florio F, Golfieri R, Grosso M, Lauretti DL, Cioni R. Trends in utilization of transarterial treatments for hepatocellular carcinoma: results of a survey by the Italian Society of Interventional Radiology. Cardiovasc Intervent Radiol 2013; 37:438-44. [PMID: 23719667 DOI: 10.1007/s00270-013-0656-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Accepted: 04/30/2013] [Indexed: 02/06/2023]
Abstract
PURPOSE This study was designed to provide an overview of the practice of locoregional treatments for HCC by the Italian centers of Interventional Radiology (IR) with particular reference to transarterial modalities. METHODS A questionnaire of 11 questions on locoregional treatment of HCC was e-mailed to 134 Italian IR centers. RESULTS The response rate was 64.9% (87/135 centers). Of 8,959 procedures in 2011, 67% were transarterial treatments, 31% percutaneous ablations, and 2% Y90-radioembolizations. Regarding (chemo)embolization, approximately 59% of procedures were performed in the intermediate stage, 28% in the early stage, and 12.8% in the advanced stage. TACE techniques varied greatly; approximately 52% of procedures were performed with drug-eluting particles and 32% with lipiodol, drug, and reabsorbable particles. In selected cases, 53 of 78 (68%) centers combine chemoembolization and ablation, whereas 28 centers (35.9%) combine Sorafenib and chemoembolization. In 2011, 13 of 78 (16.7%) responding centers performed Y90-radioembolization, with approximately 52% of procedures performed in the advanced stage and 46% in the intermediate stage. Approximately 62% of Y90-radioembolizations were performed using resin spheres and 38% using glass spheres. CONCLUSIONS With almost 9,000 procedures performed each year, locoregional treatments of HCC, most of all transarterial (chemo)embolizations, represent a major part of daily clinical practice in many Italian IR centers. The high variability in responses regarding transarterial treatments for HCC patients highlights the need for solid scientific evidence allowing better definition of clinical indications and standardization of technical approaches.
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Affiliation(s)
- Irene Bargellini
- Diagnostic and Interventional Radiology, Pisa University Hospital, Via Paradisa 2, 56100, Pisa, Italy,
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GREGORY SM, MUNNEKE GJ. Interventional radiology in liver cancer. IMAGING 2013. [DOI: 10.1259/imaging.20120010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Abstract
Image-guided ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when surgical options-including resection and transplantation-are precluded. The term image-guided tumor ablation is defined as the direct application of chemical substances or sources of energy to a focal tumor in an attempt to achieve eradication or substantial tumor destruction. Over the past 25 years, several methods for local tumor destruction have been developed and clinically tested. Radiofrequency ablation (RFA) has shown superior anticancer effect and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials, and is currently established as the standard ablative modality. Nevertheless, novel thermal and nonthermal techniques for tumor ablation-including microwave ablation and irreversible electroporation-seem to have potential to improve the efficacy of RFA and are currently undergoing clinical investigation.
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Ven Fong Z, Palazzo F, Needleman L, Brown DB, Eschelman DJ, Chojnacki KA, Yeo CJ, Rosato EL. Combined Hepatic Arterial Embolization and Hepatic Ablation for Unresectable Colorectal Metastases to the Liver. Am Surg 2012. [DOI: 10.1177/000313481207801133] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Liver-directed therapy for hepatic metastases includes: intra-arterial techniques such as trans-arterial chemoembolization (TACE) and yttrium-90 resin (90Y) microsphere radioembolization and ablative technologies: cryoablation, radiofrequency ablation, and microwave ablation. Combining embolization techniques with liver ablation may enhance the therapeutic benefit of each and result in improved patient survival. We retrospectively reviewed our experience with combined intra-arterial therapies and ablation for unresectable hepatic colorectal metastases from 1996 to 2011. Patient demographics, tumor characteristics, specific liver-directed treatments, procedure-related morbidity and mortality, and overall survival were recorded. There were 17 (53%) males and 15 (47%) females. Average age for the group was 74.1 years (median, 75.5 years). Fifteen patients (46.9%) had a single hepatic metastasis. Eleven (34%) patients had bilobar tumor distribution and seven (22%) patients had vascular invasion of the portal vein or hepatic/caval venous structures. Seven (21%) tumors were greater than 5 cm in diameter. Twenty-seven (84.4%) patients received TACE and five (15.6%) received 90Y. Fourteen (43%) were embolized before any ablation. Fifty-three per cent of patients required multiple hepatic ablation sessions. Median length of hospital stay was 1 day. There were no procedure-related mortalities and complications occurred in six (18.8%) patients. Mean follow-up for the group was 33 months. Kaplan-Meier 1-, 3-, and 5-year estimated survival was 93.8, 50.0, and 10.1 per cent, respectively. Median survival for the group was 46 months. Hepatic ablation and embolization techniques can be combined safely with minimal morbidity. In our series, we observed 5-year survival in 10 per cent of patients.
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Affiliation(s)
- Zhi Ven Fong
- Departments of Surgery, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania
| | - Francesco Palazzo
- Departments of Surgery, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania
| | - Laurence Needleman
- Departments of Radiology, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania
| | - Daniel B. Brown
- Departments of Radiology, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania
| | - David J. Eschelman
- Departments of Radiology, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania
| | - Karen A. Chojnacki
- Departments of Surgery, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania
| | - Charles J. Yeo
- Departments of Surgery, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania
| | - Ernest L. Rosato
- Departments of Surgery, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania
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Superselective particle embolization enhances efficacy of radiofrequency ablation: effects of particle size and sequence of action. Cardiovasc Intervent Radiol 2012; 36:773-82. [PMID: 23070107 DOI: 10.1007/s00270-012-0497-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Accepted: 09/07/2012] [Indexed: 01/02/2023]
Abstract
PURPOSE To evaluate the effects of particle size and course of action of superselective bland transcatheter arterial embolization (TAE) on the efficacy of radiofrequency ablation (RFA). METHODS Twenty pigs were divided into five groups: group 1a, 40-μm bland TAE before RFA; group 1b, 40-μm bland TAE after RFA; group 2a, 250-μm bland TAE before RFA; group 2b, 250-μm bland TAE after RFA and group 3, RFA alone. A total of 40 treatments were performed with a combined CT and angiography system. The sizes of the treated zones were measured from contrast-enhanced CTs on days 1 and 28. Animals were humanely killed, and the treated zones were examined pathologically. RESULTS There were no complications during procedures and follow-up. The short-axis diameter of the ablation zone in group 1a (mean ± standard deviation, 3.19 ± 0.39 cm) was significantly larger than in group 1b (2.44 ± 0.52 cm; P = 0.021), group 2a (2.51 ± 0.32 cm; P = 0.048), group 2b (2.19 ± 0.44 cm; P = 0.02), and group 3 (1.91 ± 0.55 cm; P < 0.001). The greatest volume of ablation was achieved by performing embolization with 40-μm particles before RFA (group 1a; 20.97 ± 9.65 cm(3)). At histology, 40-μm microspheres were observed to occlude smaller and more distal arteries than 250-μm microspheres. CONCLUSION Bland TAE is more effective before RFA than postablation embolization. The use of very small 40-μm microspheres enhances the efficacy of RFA more than the use of larger particles.
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Magnetic resonance-guided laser-induced thermotherapy in patients with oligonodular hepatocellular carcinoma: long-term results over a 15-year period. J Clin Gastroenterol 2012; 46:796-801. [PMID: 22955262 DOI: 10.1097/mcg.0b013e3182641806] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
GOALS To prospectively evaluate the therapeutic potential of magnetic resonance (MR)-guided laser-induced thermotherapy (LITT) in patients with oligonodular hepatocellular carcinoma. STUDY A total of 113 patients with 175 intrahepatic lesions were treated with MR-guided LITT. The Nd-YAG laser fiber was introduced with a percutaneously positioned irrigated laser application system. Qualitative and quantitative MR parameters and clinical data were evaluated. Survival data were calculated using the Kaplan-Meier method. RESULTS All patients tolerated the procedure well under local anesthesia. The total procedure time was 90 minutes. All observed complications were minor and no further treatment was necessary. Online MR thermometry allowed exact visualization of the extension of laser-induced changes and their relationship to the neighboring anatomy. Lesions up to 2 cm in diameter could be efficiently treated with a single laser application; larger lesions were treated with a dual, triple, and quadruple simultaneous application. In 98% of the patients we achieved a complete necrosis of the tumor and up to 5 mm of safety margin. The mean survival rate for all patients, with calculation started on the date of diagnosis of the HCC nodules treated with LITT, was 4.9 years (95% confidence interval, 3.6, 5.1). The median survival rate for all patients, with calculation started on the date of diagnosis of the HCC nodules treated with LITT, was 3.5 years (95% confidence interval, 2.7, 4.2). One-year survival was 95%; 2-year survival 72%, 3-year survival 54%; and 5-year survival 30%. CONCLUSIONS In intrahepatic oligonodular involvement of hepatocellular carcinoma LITT appears to be an effective therapeutic procedure.
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Lewis AL, Dreher MR. Locoregional drug delivery using image-guided intra-arterial drug eluting bead therapy. J Control Release 2012; 161:338-50. [PMID: 22285550 PMCID: PMC3351580 DOI: 10.1016/j.jconrel.2012.01.018] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2011] [Revised: 01/13/2012] [Accepted: 01/15/2012] [Indexed: 12/30/2022]
Abstract
Lipiodol-based transarterial chemoembolization (TACE) has been performed for over 3 decades for the treatment of solid tumors and describes the infusion of chemotherapeutic agents followed by embolization with particles. TACE is an effective treatment for inoperable hepatic tumors, especially hypervascular tumors such as hepatocellular carcinoma. Recently, drug eluting beads (DEBs), in which a uniform embolic material is loaded with a drug and delivered in a single image-guided step, have been developed to reduce the variability in a TACE procedure. DEB-TACE results in localization of drug to targeted tumors while minimizing systemic exposure to chemotherapeutics. Once localized in the tissue, drug is eluted from the DEB in a controlled manner and penetrates hundreds of microns of tissue from the DEB surface. Necrosis is evident surrounding a DEB in tissue days to months after therapy; however, the contribution of drug and ischemia is currently unknown. Future advances in DEB technology may include image-ability, DEB size tailored to tumor anatomy and drug combinations.
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Affiliation(s)
- Andrew L Lewis
- Biocompatibles UK Ltd, Farnham Business Park, Weydon Lane, Farnham, Surrey, GU9 8QL, UK.
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Abstract
Local-regional treatments play a key role in the management of hepatocellular carcinoma (HCC). Image-guided tumor ablation is recommended in patients with early-stage HCC when surgical options are precluded and can replace resection in selected patients. Radiofrequency (RF) ablation has shown superior anticancer effects and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials and is currently established as the standard method for local tumor treatment. Novel thermal and nonthermal techniques for tumor ablation, including microwave ablation and irreversible electroporation, seem to have potential to overcome the limitations of RF ablation and warrant further clinical investigation. Transcatheter arterial chemoembolization (TACE) is the standard of care for patients with asymptomatic noninvasive multinodular tumors in intermediate-stage disease. Embolic microspheres that have the ability to release a drug in a controlled and sustained fashion have been shown to substantially increase the safety and efficacy of TACE in comparison to conventional ethiodized oil-based regimens. The available data for radioembolization with yttrium 90 suggest that this is a potential new option for patients with HCC, and future studies should be devoted to assessments of the role of radioembolization in the treatment algorithm for HCC.
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Affiliation(s)
- Riccardo Lencioni
- Division of Diagnostic Imaging and Intervention, Department of Liver Transplantation, Hepatology, and Infectious Diseases, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy.
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Transcatheter treatment of hepatocellular carcinoma with Doxorubicin-loaded DC Bead (DEBDOX): technical recommendations. Cardiovasc Intervent Radiol 2011; 35:980-5. [PMID: 22009576 PMCID: PMC3447142 DOI: 10.1007/s00270-011-0287-7] [Citation(s) in RCA: 232] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2011] [Accepted: 09/27/2011] [Indexed: 12/16/2022]
Abstract
Tranarterial chemoembolization (TACE) has been established by a meta-analysis of randomized controlled trials as the standard of care for nonsurgical patients with large or multinodular noninvasive hepatocellular carcinoma (HCC) isolated to the liver and with preserved liver function. Although conventional TACE with administration of an anticancer-in-oil emulsion followed by embolic agents has been the most popular technique, the introduction of embolic drug-eluting beads has provided an alternative to lipiodol-based regimens. Experimental studies have shown that TACE with drug-eluting beads has a safe pharmacokinetic profile and results in effective tumor killing in animal models. Early clinical experiences have confirmed that drug-eluting beads provide a combined ischemic and cytotoxic effect locally with low systemic toxic exposure. Recently, the clinical value of a TACE protocol performed by using the embolic microsphere DC Bead loaded with doxorubicin (DEBDOX; drug-eluting bead doxorubicin) has been shown by randomized controlled trials. An important limitation of conventional TACE has been the inconsistency in the technique and the treatment schedules. This limitation has hampered the acceptance of TACE as a standard oncology treatment. Doxorubicin-loaded DC Bead provides levels of consistency and repeatability not available with conventional TACE and offers the opportunity to implement a standardized approach to HCC treatment. With this in mind, a panel of physicians took part in a consensus meeting held during the European Conference on Interventional Oncology in Florence, Italy, to develop a set of technical recommendations for the use of DEBDOX in HCC treatment. The conclusions of the expert panel are summarized.
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Nicolini A, Crespi S, Martinetti L. Drug delivery embolization systems: a physician's perspective. Expert Opin Drug Deliv 2011; 8:1071-84. [PMID: 21692688 DOI: 10.1517/17425247.2011.590472] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION The number of patients suffering from primary and secondary liver tumoral diseases is on the increase worldwide. The development of new technologies and drugs requires an increasingly multidisciplinary approach in the management of these diseases. Therapies should be based on scientifically supported guidelines and at the same time should be designed to suit the individual patient. In this decision-making process, an understanding of the advantages and disadvantages of every treatment is very important. The efficacy of transarterial chemoembolization (TACE) in improving survival and its role in the management of hepatocellular carcinoma (HCC) have been demonstrated in several clinical trials. The introduction of drug-eluting beads seems to have overcome some of the limitations of conventional TACE. AREAS COVERED This review provides an overview of the spread of primary and secondary liver cancers, then it explains the basis for the use of conventional TACE and its potential benefits and, finally, outlines its clinical application and possible future uses. EXPERT OPINION The management of the treatment of focal liver lesions is a difficult process, which must involve various specialists such as the interventional radiologist. The use of drug-eluting microspheres seems to improve the results of TACE both in HCC and in colorectal liver metastases.
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Affiliation(s)
- Antonio Nicolini
- IRCCS-Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano, Interventional radiology, Via Francesco Sforza 35, Milano 20100, Italy.
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Abstract
Locoregional therapies for hepatocellular carcinoma have progressed greatly in the last 30 years, beginning with the introduction of chemoembolization. Embolization techniques have evolved with the use of drug-eluting beads and radioembolization with yttrium-90. In the last 10 years, several new ablation techniques were developed including radiofrequency ablation, microwave ablation, cryoablation, laser ablation, and irreversible electroporation. Isolated or in combination, these techniques have already shown that they can improve patient survival and/or provide acceptable palliation.
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Affiliation(s)
- Marcelo Guimaraes
- Division of Vascular & Interventional Radiology, Medical University of South Carolina, 25 Courtenay Drive, MSC 226, Charleston, SC 29425, USA.
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46
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Bargellini I. Hepatocellular carcinoma: MR staging and therapeutic decisions. ACTA ACUST UNITED AC 2011; 37:231-8. [PMID: 21479803 DOI: 10.1007/s00261-011-9735-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Staging of hepatocellular carcinoma (HCC) represents a controversial and complex topic, since prognosis is largely dependent on several variables other than tumor extension, such liver function and general clinical conditions. Up to now, there is no agreement regarding the most reliable clinical staging system for HCC. Ideally, the staging system should be simple and easily obtainable and should not be influenced by differences in patient populations. So far, in Western countries, the Barcelona Clinic for Liver Cancer (BCLC) staging system represents the most frequently adopted classification. It is simple and guides the clinicians through the therapeutic decision process. Magnetic resonance imaging represents the most proper imaging modality for correct staging of HCC, providing high accuracy in evaluating tumor extension as well as tumor response to treatment (after percutaneous ablation, transarterial chemoembolization, or molecular-targeted therapy). The present review describes the most frequently used staging systems and the treatment options that are recommended for the different stages of the disease.
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Affiliation(s)
- Irene Bargellini
- Department of Diagnostic and Interventional Radiology, Pisa University Hospital, Via Paradisa 2, 56124, Pisa, Italy.
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Lewis AL, Holden RR. DC Bead embolic drug-eluting bead: clinical application in the locoregional treatment of tumours. Expert Opin Drug Deliv 2011; 8:153-69. [PMID: 21222553 DOI: 10.1517/17425247.2011.545388] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION DC Bead is an embolic drug-eluting bead designed to be loaded with chemotherapeutic agents (such as doxorubicin and irinotecan), delivered intra-arterially into tumor blood vessels to block nutrient flow and then to deliver the drug locally in a sustained fashion. This product is finding increasing use in the treatment of patients with both primary and secondary liver cancers. AREAS COVERED This review positions DC Bead in the field of targeted embolic drug delivery and with respect to other competitive technologies in the treatment of liver cancer. An overview of the studies that demonstrate the product's performance, safety and efficacy is presented. The clinical application of the doxorubicin loaded DC Bead is firstly reviewed, in the context of treatment of patients with various stages of hepatocellular carcinoma. Its combination with other therapies is also discussed, together with consideration of the treatment of other liver tumors. Secondly, the use of irinotecan loaded DC Bead, primarily for the treatment of colorectal cancer metastases to the liver, but also some additional rare metastases, is summarized. EXPERT OPINION An opinion is proffered as to how this technology and its application is evolving, illustrating a move towards synergistic combination therapies and into other cancer indications.
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Affiliation(s)
- Andrew L Lewis
- Biocompatibles UK Ltd, Farnham Business Park, Weydon Lane, Farnham, Surrey, UK.
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48
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Widenmeyer M, Shebzukhov Y, Haen SP, Schmidt D, Clasen S, Boss A, Kuprash DV, Nedospasov SA, Stenzl A, Aebert H, Wernet D, Stevanović S, Pereira PL, Rammensee HG, Gouttefangeas C. Analysis of tumor antigen-specific T cells and antibodies in cancer patients treated with radiofrequency ablation. Int J Cancer 2010; 128:2653-62. [PMID: 20715115 DOI: 10.1002/ijc.25601] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2010] [Accepted: 07/20/2010] [Indexed: 01/22/2023]
Abstract
Radiofrequency (RF) ablation is a minimally invasive technique routinely applied for the treatment of primary and secondary liver tumors. It induces cell death by thermal coagulative necrosis of tumor tissues, whereas cellular metabolism can still take place in a transition zone surrounding the necrotic area. An increase in heat shock protein expression occurs shortly after treatment, suggesting that the induction of activating signals may stimulate the host immune system. In addition, various effects on immune effectors have also been observed, including stimulation of tumor-directed T lymphocytes. Here, we prospectively assessed the activation of tumor antigen-specific antibodies, as well as antigen-specific CD4(+) and CD8(+) T cells in patients suffering from primary or secondary malignancies and treated by RF ablation with or without concomitant chemotherapy. An increase of antibodies (in 4 patients of 49), CD4(+) T cells or CD8(+) T cells (in 2 patients of 49) could be detected several weeks to months following intervention. These findings suggest that in addition to the local control of tumor growth, RF ablation can provide the appropriate conditions for activating tumor-antigen specific immune responses.
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Affiliation(s)
- Melanie Widenmeyer
- Department of Immunology, Institute for Cell Biology, Eberhard Karls University, Auf der Morgenstelle 15, 72076 Tuebingen, Germany
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49
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Yang W, Ahmed M, Elian M, Hady ESA, Levchenko TS, Sawant RR, Signoretti S, Collins M, Torchilin VP, Goldberg SN. Do liposomal apoptotic enhancers increase tumor coagulation and end-point survival in percutaneous radiofrequency ablation of tumors in a rat tumor model? Radiology 2010; 257:685-96. [PMID: 20858851 DOI: 10.1148/radiol.10100500] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
PURPOSE To characterize effects of combining radiofrequency (RF) ablation with proapoptotic intravenous liposome-encapsulated paclitaxel and doxorubicin on tumor destruction, apoptosis and heat-shock protein (HSP) production, intratumoral drug accumulation, and end-point survival. MATERIALS AND METHODS R3230 mammary adenocarcinomas (n = 177) were implanted in 174 rats in this animal care committee-approved study. Tumors received (a) no treatment, (b) RF ablation, (c) paclitaxel, (d) RF ablation followed by paclitaxel (RF ablation-paclitaxel), (e) paclitaxel before RF ablation (paclitaxel-RF ablation), (f) RF ablation followed by doxorubicin (RF ablation-doxorubicin), (g) paclitaxel followed by doxorubicin without RF ablation (paclitaxel-doxorubicin), or (h) paclitaxel before RF ablation, followed by doxorubicin (paclitaxel-RF ablation-doxorubicin). Tumor coagulation area and diameter were compared at 24-96 hours after treatment. Intratumoral paclitaxel uptake with and without RF ablation were compared. Immunohistochemical staining revealed cleaved caspase-3 and 70-kDa HSP (HSP70) expression. Tumors were randomized into eight treatment arms for Kaplan-Meier analysis of defined survival end-point (3.0-cm diameter). RESULTS Paclitaxel-RF ablation increased tumor coagulation over RF ablation or paclitaxel (mean, 14.0 mm ± 0.9 [standard deviation], 6.7 mm ± 0.6, 2.5 mm ± 0.6, respectively; P < .001). Paclitaxel-RF ablation-doxorubicin had similar tumor coagulation (P < .05), compared with paclitaxel-RF ablation, at 24 and 96 hours. Mean intratumoral paclitaxel accumulation for paclitaxel-RF ablation (6.76 μg/g ± 0.35) and RF ablation-paclitaxel (9.28 μg/g ± 0.87) increased over that for paclitaxel (0.63 μg/g ± 0.25, P < .001). Paclitaxel substantially increased apoptosis and decreased HSP70 expression at coagulation margin. Mean end-point survival for paclitaxel-RF ablation-doxorubicin (56.8 days ± 25.3) was greater, compared with that for paclitaxel-RF ablation or RF ablation-paclitaxel (17.6 days ± 2.5), RF ablation-doxorubicin (30.3 days ± 4.9, P < .002), or paclitaxel-doxorubicin (27.9 days ± 4.1, P < .001). CONCLUSION Selecting adjuvant liposomal chemotherapies (paclitaxel, doxorubicin) to target cellular apoptosis and HSP production effectively increases RF ablation-induced tumor coagulation and end-point survival, and combined multidrug approach results in even better outcomes. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100500/-/DC1.
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Affiliation(s)
- Wei Yang
- Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA
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50
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Wang JH, Tung HD, Chen TY, Hung CH, Chen CH, Changchien CS, Hu TH, Lee CM, Lu SN. Radiofrequency ablation of small hepatocellular carcinoma with intravenous pegylated liposomal doxorubicin. Hepatol Int 2010; 5:567-74. [PMID: 21442054 DOI: 10.1007/s12072-010-9215-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2010] [Accepted: 08/31/2010] [Indexed: 11/28/2022]
Abstract
PURPOSE Synergy between radiofrequency ablation (RFA) and chemotherapy was demonstrated for liver malignancy. We assess the efficacy of intravenous pegylated liposomal doxorubicin (PLD) for RFA in patients with small hepatocellular carcinoma (HCC). METHODS This study was designed as a non-randomized control trial. Patients received either PLD (20 mg) intravenously before RFA, or standard RFA alone. Computed tomography was performed immediately and 4 weeks after RFA to obtain ablative diameter, area and volume for each tumor. The changes in ablation size were analyzed by paired images for each tumor. All patients were followed up regularly. RESULTS A total of 24 patients with 29 HCCs, including 12 patients with 16 tumors (mean 2.2 cm ± 0.9) in the PLD and RFA group, and 12 patients with 13 tumors (2.4 cm ± 0.5) in the RFA alone group, were enrolled. The ablative diameter, area and volume significantly decreased 4 weeks after RFA. The ablative volume decrease was significantly greater for the RFA alone group than for the combination group (26.1 vs. 12.1%, p = 0.018). The 3-year cumulative tumor progression and survival rates did not differ significantly between the two groups. CONCLUSION Intravenous PLD before RFA reduced contraction of ablative volume and might have no impact on tumor progression and survival in patients with small HCC after RFA.
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