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Mukund A, Kumar N, Srivastava A, Baby A. Transarterial Chemoembolization: A Consistent and Continuously Evolving Therapy for Hepatocellular Carcinoma. J Clin Exp Hepatol 2025; 15:102538. [PMID: 40226387 PMCID: PMC11985049 DOI: 10.1016/j.jceh.2025.102538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 02/25/2025] [Indexed: 04/15/2025] Open
Abstract
Since its introduction in 1977, transarterial chemoembolization (TACE) has widely been accepted treatment for unresectable intermediate stage hepatocellular carcinoma (HCC). Conventional TACE (c-TACE) uses an emulsion of chemotherapeutic agent and ethiodized oil with subsequent embolization of the feeding artery using gelatin sponge. Drug eluting beads (DEB) were introduced in clinical practice in the 2000s and have since been used as an alternative to c-TACE with better outcomes, especially in larger tumors. Considering the widespread use of TACE in HCC, it is important to revisit the current knowledge and the advances that have developed for better safety and efficacy. This article aims to emphasize on the current knowledge and importance of TACE, touch upon the technical aspects including post-TACE care, response assessment, and discontinuation strategies and highlight the recent advances in the technology, catheters, and embolization particles. Thus, despite a rapid change in treatment algorithms and availability of newer drugs for HCC, TACE will remain an integral part of HCC treatment alone or in combination with other therapies.
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Affiliation(s)
- Amar Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India
| | - Niraj Kumar
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India
| | - Amol Srivastava
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India
| | - Akhil Baby
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India
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Higashihara H, Kimura Y, Ono Y, Tanaka K, Tomiyama N. Effective Utilization of Conventional Transarterial Chemoembolization and Drug-eluting Bead Transarterial Chemoembolization in Hepatocellular Carcinoma: A Guide to Proper Usage. INTERVENTIONAL RADIOLOGY (HIGASHIMATSUYAMA-SHI (JAPAN) 2025; 10:e20230009. [PMID: 40384901 PMCID: PMC12078087 DOI: 10.22575/interventionalradiology.2023-0009] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 06/13/2023] [Indexed: 05/20/2025]
Abstract
Transarterial chemoembolization is still an effective treatment option for hepatocellular carcinoma worldwide and is categorized into conventional transarterial chemoembolization with ethiodized oil transarterial chemoembolization and transarterial chemoembolization with drug-eluting spherical material transarterial chemoembolization. Several randomized controlled trials conducted in Europe have shown the equivalent efficacy of ethiodized oil transarterial chemoembolization and drug-eluting spherical material transarterial chemoembolization. However, a recent randomized controlled trials in Japan established the superiority of ethiodized oil transarterial chemoembolization in terms of complete response rates although higher liver toxicity for ethiodized oil transarterial chemoembolization. Nevertheless, the survival advantage of ethiodized oil transarterial chemoembolization is yet to be substantiated. The adverse effects of drug-eluting spherical material transarterial chemoembolization are milder than those of ethiodized oil transarterial chemoembolization, rendering drug-eluting spherical material transarterial chemoembolization an advantageous option for patients with bilobar tumors and impaired liver function/performance status. This article aims to provide an overview of these embolization techniques and a review of recent literature.
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Affiliation(s)
- Hiroki Higashihara
- Department of High-Precision Image-Guided Percutaneous Intervention, Osaka University Graduate School of Medicine, Japan
| | - Yasushi Kimura
- Department of High-Precision Image-Guided Percutaneous Intervention, Osaka University Graduate School of Medicine, Japan
| | - Yusuke Ono
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Kaishu Tanaka
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Noriyuki Tomiyama
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
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Luo C, Xiang H, Tan J. The efficacy of transcatheter arterial chemoembolization for hepatocellular carcinoma: is the alteration of the inflammation index important? Front Med (Lausanne) 2025; 12:1543903. [PMID: 40160321 PMCID: PMC11949957 DOI: 10.3389/fmed.2025.1543903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 03/03/2025] [Indexed: 04/02/2025] Open
Abstract
Introduction Transcatheter arterial chemoembolization (TACE) is widely applied for locoregional malignant lesions control in intermediate and selected advanced hepatocellular carcinoma (HCC). Various inflammation indices, such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammatory index (SII), and Lymphocyte-to-C Reactive Protein Ratio (LCR) have been explored as tools for predicting the efficacy of TACE. However, the role and predictive value for dynamic changes of peripheral inflammatory indicators pre- and post-TACE remains unclear. Objective To explore the association between the alteration in inflammatory index and the efficacy and prognosis of TACE and to provide more evidence for early prediction of the efficacy of TACE. Methods This was a retrospective single-center study. HCC patients who received TACE as initial treatment were enrolled. The relationship between the alteration of inflammation indices (calculated as post-TACE minus pre-TACE measurements) and TACE efficacy and prognosis was investigated. Progression-free survival (PFS) was the primary endpoint, and treatment efficacy was evaluated based on mRECIST criteria. Results Before propensity score matching (PSM), the change in LMR was significantly associated with treatment effective rate, with the unelevated ΔLMR group achieving a 79.4% treatment effective rate compared to 36.4% in the elevated group (p < 0.001). The estimated median PFS was 9.7 months and 4.5 months in the unelevated and elevated group, with a significant difference (p = 0.016). After PSM, the treatment effective rate was 48.7 and 38.5% (p = 0.214), and the estimated median PFS was 8.9 and 5.5 months (p = 0.173) for the unelevated and elevated group, respectively. Conclusion Our study demonstrated that alteration of indices of peripheral inflammation, including ΔNLR, ΔLMR, ΔSII, and ΔPLR, may not be valuable prognostic markers for HCC patients who received TACE.
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Affiliation(s)
- Chao Luo
- Department of Interventional Vascular Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
| | - Hua Xiang
- Department of Interventional Vascular Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
- Department of Interventional Vascular Surgery, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Jie Tan
- Department of Interventional Vascular Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
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Lanza C, Ascenti V, Amato GV, Pellegrino G, Triggiani S, Tintori J, Intrieri C, Angileri SA, Biondetti P, Carriero S, Torcia P, Ierardi AM, Carrafiello G. All You Need to Know About TACE: A Comprehensive Review of Indications, Techniques, Efficacy, Limits, and Technical Advancement. J Clin Med 2025; 14:314. [PMID: 39860320 PMCID: PMC11766109 DOI: 10.3390/jcm14020314] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 12/17/2024] [Accepted: 12/28/2024] [Indexed: 01/27/2025] Open
Abstract
Transcatheter arterial chemoembolization (TACE) is a proven and widely accepted treatment option for hepatocellular carcinoma and it is recommended as first-line non-curative therapy for BCLC B/intermediate HCC (preserved liver function, multifocal, no cancer-related symptoms) in patients without vascular involvement. Different types of TACE are available nowadays, including TAE, c-TACE, DEB-TACE, and DSM-TACE, but at present there is insufficient evidence to recommend one TACE technique over another and the choice is left to the operator. This review then aims to provide a comprehensive overview of the current literature on indications, types of procedures, safety, and efficacy of different TACE treatments.
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Affiliation(s)
- Carolina Lanza
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Velio Ascenti
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Gaetano Valerio Amato
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Giuseppe Pellegrino
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Sonia Triggiani
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Jacopo Tintori
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Cristina Intrieri
- Postgraduate School in Diangostic Imaging, Università degli Studi di Siena, 20122 Milan, Italy;
| | - Salvatore Alessio Angileri
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Pierpaolo Biondetti
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Serena Carriero
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Pierluca Torcia
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Anna Maria Ierardi
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Gianpaolo Carrafiello
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
- Faculty of Health Science, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy
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Chang PY, Lee RC, Liang PC, Liu YS, Chuang VP, Wu DK, Cheng YF, Huang JI, Tseng HS, Hung CF, Wu RH, Chern MC, Cheng HM, Wu CH, Cheng SM, Chiang CL, Liang HL. Multidisciplinary Taiwan consensus for the use of conventional TACE in hepatocellular carcinoma treatment. Front Oncol 2023; 13:1186674. [PMID: 37427137 PMCID: PMC10328116 DOI: 10.3389/fonc.2023.1186674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as "conventional TACE" (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.
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Affiliation(s)
- Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Yi-Sheng Liu
- Department of Medical Imagine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Vicent P. Chuang
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Ding-Kwo Wu
- Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jen-I. Huang
- Department of Radiology, Tungs’ Taichung Metroharbor Hospital, Taichung, Taiwan
| | - Hsiuo-Shan Tseng
- Department of Radiology, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Chien-Fu Hung
- Department of Radiology, Chang−Gung Memorial Hospital, Taoyuan, Taiwan
| | - Reng-Hong Wu
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Chih Chern
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Hua-Ming Cheng
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chih-Horng Wu
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - She-Meng Cheng
- Department of Radiology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chia-Ling Chiang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Stewart RJ, Sima M, Karz J, Jones JP. Material characterization of GPX ®: A versatile in situ solidifying embolic platform technology. Front Bioeng Biotechnol 2023; 11:1095148. [PMID: 36726745 PMCID: PMC9885798 DOI: 10.3389/fbioe.2023.1095148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 01/02/2023] [Indexed: 01/19/2023] Open
Abstract
Endovascular embolization is a minimally invasive procedure during which blood flow to targeted tissues is selectively occluded. The list of clinical indications for embolization continues to expand. Liquid embolic agents are injectable compositions that transition into a solid or semi-solid form when introduced into blood vessels. The mechanism that triggers the liquid-to-solid transition is a key distinguishing feature of liquid embolic agents. GPX is a waterborne liquid embolic agent comprising oppositely charged polyelectrolytes: polyguanidinum and inorganic polyphoshate. In situ solidification is driven by electrostatic condensation of the polyelectrolytes, triggered by ionic strength differentials. We report in vitro characterization of the material properties of GPX, it is in vivo effectiveness in acute animal studies, and its potential for chemoembolization. The viscosity of GPX can be varied over a wide range by adjusting the polyguanidinium MW and/or concentration. Formulation of GPX with either tantalum microparticles (30 wt%) or iodinated radiocontrast agents (300 mgI ml-1) did not significantly change the flow behavior of GPX; the viscosity was independent of shear rate and remained within a clinically practical range (80-160 cP). Formulation of GPX with doxorubicin substantially increased viscosity at low shear rates and resulted in a power law dependence on shear rate. High contrast and effective vascular occlusion were demonstrated in both swine kidneys and rete mirabile. Contrast from iodinated compounds was temporary, dissipating within hours. The doxorubicin in vitro release profile was linear over 90 days. The results demonstrate that GPX is a versatile liquid embolic platform that can be formulated with a wide range of viscosities injectable at clinically practical flow rates, with either transient or permanent contrast, and that can provide prolonged zero-order delivery of doxorubicin to embolized tissues.
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Affiliation(s)
- Russell J. Stewart
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, United States,*Correspondence: Russell J. Stewart,
| | - Monika Sima
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, United States
| | - Jessica Karz
- Fluidx Medical Technology, Inc., Salt Lake City, UT, United States
| | - Joshua P. Jones
- Fluidx Medical Technology, Inc., Salt Lake City, UT, United States
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Renzulli M, Peta G, Vasuri F, Marasco G, Caretti D, Bartalena L, Spinelli D, Giampalma E, D'Errico A, Golfieri R. Standardization of conventional chemoembolization for hepatocellular carcinoma. Ann Hepatol 2021; 22:100278. [PMID: 33129978 DOI: 10.1016/j.aohep.2020.10.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 10/19/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Conventional transarterial chemoembolization (cTACE) has several limitations due to the lack of standardization. The aim of this study was to evaluate the chemical and physical characteristics and behaviors over time of emulsions for cTACE and to assess intra- and inter-operator variabilities in the preparation processes. MATERIALS AND METHODS This in vitro study involved evaluation of emulsions for cTACE prepared using two methods: water-in-oil (WiO) and chemotherapeutic-in-oil (CiO). Three emulsions were prepared with each method and obtained after 20, 50, and 100 pumping exchanges. A drop from each final mixture was analyzed via light microscopy (time 1) and after 5, 10, 15, and 20min since the end of preparation. After 20min, all preparations were re-mixed and new drops were re-evaluated. The intra- and inter-operator variabilities were analyzed. RESULTS The mean droplet diameter decreased non-significantly when the number of pumping exchanges increased and increased significantly over time for both WiO and CiO. The droplets returned to their initial diameters after re-mixing. There were no significant differences in the intra- and inter-operator variabilities (P>0.01). CONCLUSIONS Any interventional radiologist, regardless of their experience, may prepare these emulsions. These data may represent a set of instructions to standardize cTACE.
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Affiliation(s)
- Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy.
| | - Giuliano Peta
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Francesco Vasuri
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Giovanni Marasco
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Daniele Caretti
- "Toso Montanari" Industrial Chemistry Department, University of Bologna, Bologna, Italy
| | - Laura Bartalena
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Daniele Spinelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | | | - Antonietta D'Errico
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
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Ebeling Barbier C, Heindryckx F, Lennernäs H. Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma. Int J Mol Sci 2021; 22:ijms222313051. [PMID: 34884853 PMCID: PMC8658005 DOI: 10.3390/ijms222313051] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 11/26/2021] [Accepted: 11/29/2021] [Indexed: 02/07/2023] Open
Abstract
Because diagnostic tools for discriminating between hepatocellular carcinoma (HCC) and advanced cirrhosis are poor, HCC is often detected in a stage where transarterial chemoembolization (TACE) is the best treatment option, even though it provides a poor survival gain. Despite having been used worldwide for several decades, TACE still has many limitations. First, there is a vast heterogeneity in the cellular composition and metabolism of HCCs as well as in the patient population, which renders it difficult to identify patients who would benefit from TACE. Often the delivered drug does not penetrate sufficiently selectively and deeply into the tumour and the drug delivery system is not releasing the drug at an optimal clinical rate. In addition, therapeutic effectiveness is limited by the crosstalk between the tumour cells and components of the cirrhotic tumour microenvironment. To improve this widely used treatment of one of our most common and deadly cancers, we need to better understand the complex interactions between drug delivery, local pharmacology, tumour targeting mechanisms, liver pathophysiology, patient and tumour heterogeneity, and resistance mechanisms. This review provides a novel and important overview of clinical data and discusses the role of the tumour microenvironment and lymphatic system in the cirrhotic liver, its potential response to TACE, and current and possible novel DDSs for locoregional treatment.
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Affiliation(s)
| | - Femke Heindryckx
- Department of Medical Cell Biology, Uppsala University, 751 23 Uppsala, Sweden;
| | - Hans Lennernäs
- Department of Pharmaceutical Biosciences, Uppsala University, 751 23 Uppsala, Sweden
- Correspondence: ; Tel.: +46-18-471-4317; Fax: +46-18-471-4223
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9
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Higashihara H, Ono Y, Tanaka K, Tomotake K, Tomiyama N. Recent technical advances in conventional transarterial chemoembolization for hepatocellular carcinoma in Japan. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2021. [DOI: 10.18528/ijgii210042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Hiroki Higashihara
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yusuke Ono
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kaisyu Tanaka
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kosuke Tomotake
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Noriyuki Tomiyama
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
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Lucatelli P, Burrel M, Guiu B, de Rubeis G, van Delden O, Helmberger T. CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation. Cardiovasc Intervent Radiol 2021; 44:1851-1867. [PMID: 34694454 DOI: 10.1007/s00270-021-02968-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022]
Abstract
This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for performing transarterial chemoembolisation. It has been developed by an expert writing group under the guidance of the CIRSE Standards of Practice Committee. It will encompass all technical details reflecting European practice of different TACE procedures (Lp-TACE, DEM-TACE, DSM-TACE, b-TACE) as well as revising the existing literature on the various clinical indications (HCC, mCRC, ICC, NET). Finally, new frontiers of development will also be discussed.
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Affiliation(s)
- Pierleone Lucatelli
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy.
| | - Marta Burrel
- Radiology Department, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Boris Guiu
- Department of Radiology, Montpellier School of Medicine, St-Eloi University Hospital, Montpellier, France
| | - Gianluca de Rubeis
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy
- Department of Diagnostic Radiology, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Otto van Delden
- Department of Interventional Radiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Thomas Helmberger
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, Bogenhausen Hospital, Munich, Germany
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Efficacy of Combined Therapy with Drug-Eluting Beads-Transcatheter Arterial Chemoembolization Followed by Conventional Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multi-Center Study. Cancers (Basel) 2021; 13:cancers13184605. [PMID: 34572832 PMCID: PMC8468113 DOI: 10.3390/cancers13184605] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 09/06/2021] [Accepted: 09/09/2021] [Indexed: 02/08/2023] Open
Abstract
Simple Summary Drug-eluting beads-transcatheter chemoembolization (DEB-TACE) has recently been performed. However, local recurrence of HCC at the tumor margins is often observed. Conventional transcatheter chemoembolization (cTACE) comprises accumulating lipiodol-containing anticancer drugs into the drainage area, which is the first invasive site of hepatocellular carcinoma (HCC). We evaluate the therapeutic effect of DEB-TACE followed by cTACE in patients with intermediate stage HCC. HCC patients were divided into two groups: one group received DEB-TACE followed by cTACE (cTACE group) and the other group received only DEB-TACE (non-cTACE group). The complete response (CR) rate was significantly higher in the cTACE group than in the non-TACE group. The only factor that increased the complete response rate in the cTACE group was the number of tumors. The overall survival (OS) rate of CR patients was higher than that of non-CR patients in the cTACE group. cTACE group adverse events included severe thrombocytopenia but only in one patient. The combined therapy with DEB-TACE followed by cTACE may be useful for HCC patients. Abstract EB-TACE has recently been performed because of its lower hepatotoxicity compared to cTACE in less advanced HCC. However, local recurrence at the tumor margins is often observed after DEB-TACE. cTACE involves filling the intratumoral sinusoids with lipiodol-containing anticancer drugs and accumulating in the drainage area, which is the first site of HCC recurrence. The aim of this study is to evaluate the therapeutic effect of DEB-TACE followed by cTACE in HCC patients. Between 2014 and 2020, 65 patients with Barcelona clinic liver cancer (BCLC) stage B (intermediate stage) of HCC were enrolled and divided into two groups: one group received DEB-TACE followed by cTACE (cTACE group) and the other group received only DEB-TACE (non-cTACE group). Sixty-five patients were medically followed. The median observation time was 14 ± 13.1 months after the first DEB-TACE and outcomes were analyzed for multiple factors. Results: The complete response rate was significantly higher in the cTACE group than in the non-TACE group. The analysis showed that the only factor that increased the CR rate in the cTACE group was the total tumor number (less than four). The OS rate of CR patients was higher than that of non-CR patients in the cTACE group. Adverse events in the cTACE group included severe thrombocytopenia but only in one of twenty-seven patients. Conclusions: The combined therapy with DEB-TACE followed by cTACE may be a new effective therapeutic strategy for the intermediate stage of HCC patients.
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He C, Zeng W, Su Y, Sun R, Xiao Y, Zhang B, Liu W, Wang R, Zhang X, Chen C. Microfluidic-based fabrication and characterization of drug-loaded PLGA magnetic microspheres with tunable shell thickness. Drug Deliv 2021; 28:692-699. [PMID: 33818236 PMCID: PMC8023598 DOI: 10.1080/10717544.2021.1905739] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
To overcome the shortcoming of conventional transarterial chemoembolization (cTACE) like high systemic release, a novel droplet-based flow-focusing microfluidic device was fabricated and the biocompatible poly(lactic-co-glycolic acid) (PLGA) magnetic drug-eluting beads transarterial chemoembolization (TACE) microspheres with tunable size and shell thickness were prepared via this device. Paclitaxel, as a model active, was loaded through O/O/W emulsion method with high efficiency. The size and the shell thickness vary when adjusting the flow velocity and/or solution concentration, which caters for different clinical requirements to have different drug loading and release behavior. Under the designed experimental conditions, the average diameter of the microspheres is 60 ± 2 μm and the drug loading efficiency has reached 6%. The drug release behavior of the microspheres shows the combination of delayed release and smoothly sustained release profiles and the release kinetics differ within different shell thickness. The microspheres also own the potential of magnetic resonance imaging (MRI) visuality because of the loaded magnetic nanoparticles. The microsphere preparation method and device we proposed are simple, feasible, and effective, which have a good application prospect.
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Affiliation(s)
- Chunpeng He
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
| | - Wenxin Zeng
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
| | - Yue Su
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
| | - Ruowei Sun
- Hunan Zaochen Nanorobot Co., Ltd, Liuyang, China
| | - Yin Xiao
- Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China
| | - Bolun Zhang
- Hunan Zaochen Nanorobot Co., Ltd, Liuyang, China
| | - Wenfang Liu
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
| | | | - Xun Zhang
- Hunan Zaochen Nanorobot Co., Ltd, Liuyang, China
| | - Chuanpin Chen
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
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Higashihara H, Osuga K, Onishi H, Nakamoto A, Tsuboyama T, Tomiyama N. The diagnostic value of dual-phase cone-beam CT during hepatic arteriography in transarterial chemoembolization for hepatocellular carcinoma. Medicine (Baltimore) 2021; 100:e24902. [PMID: 33761647 PMCID: PMC9281990 DOI: 10.1097/md.0000000000024902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 02/01/2021] [Indexed: 01/05/2023] Open
Abstract
To evaluate the diagnostic value of dual-phase cone beam CT during hepatic arteriography (CBCTHA) for hepatocellular carcinoma (HCC).Thirty seven patients with unresectable HCC underwent the dual-phase CBCTHA prior to transarterial chemoembolization (TACE). Three blinded observers independently reviewed and compared the first phase CBCTHA images alone and the dual phase CBCTHA images. Diagnostic accuracy was evaluated by the alternative free-response receiver operating characteristic method (Area under the curve: Az value). Sensitivities were analyzed with the paired t test. The analysis was performed for overall HCCs, HCCs up to 1 cm and those larger than 1 cm.For all HCCs and HCCs up to 1 cm, Az value and sensitivity showed no significant difference between the first-phase CBCTHA alone and the dual-phase CBCTHA (Az: 0.81 vs 0.88, P = .07, 0.79 and 0.85, P = .14, sensitivity: 0.61 and 0.73, P = .11, 0.41 and 0.52, P = .33, respectively). For HCCs larger than 1 cm, the mean Az value and sensitivity for the dual-phase CBCTHA were significantly higher than those for the first phase CBCTHA alone (Az: 0.96 vs 0.92, P = .008, sensitivity: 0.85 vs 0.75, P = .013, respectively).The diagnostic accuracy of the dual-phase CBCTHA was superior to that of the first phase CBCTHA alone in the diagnosis of HCC larger than 1 cm.
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Affiliation(s)
- Hiroki Higashihara
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita
| | - Keigo Osuga
- Department of Radiology, Osaka Medical College, 2-7 Daigakucho, Takatsuki, Osaka, Japan
| | - Hiromitsu Onishi
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita
| | - Atsushi Nakamoto
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita
| | - Takahiro Tsuboyama
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita
| | - Noriyuki Tomiyama
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita
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Shah O, Hussain M, Shera T, Choh N, Shaheen F, Gojwari T, Bhat G, Gulzar GM. Transarterial chemoembolization of hepatocellular carcinoma: Can intraprocedural DYNA computed tomography serve as a guiding tool for the interventionist? JOURNAL OF CURRENT RESEARCH IN SCIENTIFIC MEDICINE 2021. [DOI: 10.4103/jcrsm.jcrsm_19_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Mohammadifard M, Ghanaati H, Mohammadifard M. A review of applying transarterial chemoembolization (TACE) method for management of hepatocellular carcinoma. J Family Med Prim Care 2021; 10:3553-3560. [PMID: 34934646 PMCID: PMC8653440 DOI: 10.4103/jfmpc.jfmpc_2347_20] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 06/16/2021] [Accepted: 06/28/2021] [Indexed: 12/09/2022] Open
Abstract
Liver cancer is one of the most ordinary reasons for death among cancers. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. In spite of the fact that various remedial methods have been approved particularly the survival effects of the transcatheter arterial chemoembolization (TACE) method have been accomplished widely in the HCC treatment. By applying the TACE method correctly, good survival outcomes can be achieved without harmfully affecting the hepatic functions. Transarterial chemoembolization mixes the effect of avascular necrosis (AVN) with the effect of regional chemotherapy those are under the influence of arterial embolization. By knowing the fact that the metastases of liver cancer and also perfusion indices in hepatocellular carcinoma (HCC) are via hepatic arteries, doctors chose the TACE method for the treatment of liver cancer. On the other hand, in this method, the radiologists can easily convey antitumor remedies via the arteries. Anyway, medium-level HCC is a sensitive stage of the heterogeneous disease that many patients suffer from, so specialists must consider it as a hazardous syndrome. The TACE procedure could be applied just in cases that the liver function of patients is appropriate yet, the patient liver portal vein do not have any problems and the patients do not have ascites disorder. This review is aimed to figure out the evident advantages of TACE especially by a comprehensive view on the medium level HCC. Because of that this treatment method is suggested as a first-line remedy. At last, the future landscape of the initial factors of research in managing HCC disorders have been summarized.
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Chiu SH, Chang PY, Shih YL, Huang WY, Ko KH, Chang WC, Huang GS. Efficacy and Safety of Supplemental Transarterial Chemoembolization Through Extrahepatic Collateral Arteries with Drug-eluting Beads: Treatment for Unresectable Hepatocellular Carcinoma. DRUG DESIGN DEVELOPMENT AND THERAPY 2020; 14:5029-5041. [PMID: 33235441 PMCID: PMC7680099 DOI: 10.2147/dddt.s266470] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 10/08/2020] [Indexed: 12/20/2022]
Abstract
Purpose To evaluate the therapeutic efficacy and safety of supplement transarterial chemoembolization (TACE) with drug-eluting beads TACE (DEB-TACE) through extrahepatic collateral (EHC) arteries for the treatment of hepatocellular carcinoma (HCC). Patients and Methods In this retrospective study, 61 unresectable HCC patients with treatment-naïve EHC blood supplies who received TACE from January 2016 to March 2019 were enrolled; of these patients, 42 (68.9%) received DEB-TACE, and 19 (31.1%) received cTACE. The hepatic tumor feeding arteries were treated in the same TACE session if it presented. The tumor response, time-to-progression (TTP), and overall survival (OS) were analyzed. Safety was assessed based on the occurrence of liver function deterioration and major complications within three months after TACE. Results DEB-TACE showed better efficacy than cTACE in the disease control rate (p=0.001), overall response rate (p=0.005), the TTP (eight months vsthree months, p=0.002) and the OS (23.8 months vs nine months, p=0.045). Nine patients in the DEB-TACE group and one patient in the cTACE group were downstaged to resection or liver transplantation (21.4% vs 5.3%, p=0.151). DEB-TACE and cTACE have no difference in the acute and chronic liver toxicity. With regard to complications, there was no significant difference in the occurrence of both major (16.7% vs 21.1%, p=0.72) and minor (57.1% vs 47.4%, p=0.48) complications between DEB-TACE and cTACE. Conclusion DEB-TACE through EHC arteries has a potential therapeutic effect in the treatment of unresectable HCC, with comparable safety compared with cTACE.
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Affiliation(s)
- Sung-Hua Chiu
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Ping-Ying Chang
- Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wen-Yen Huang
- Department of Radiotherapy, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Kai-Hsiung Ko
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Chou Chang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Guo-Shu Huang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Link TW, Santillan A, Patsalides A. Intra-arterial neuroprotective therapy as an adjunct to endovascular intervention in acute ischemic stroke: A review of the literature and future directions. Interv Neuroradiol 2020; 26:405-415. [PMID: 32423272 DOI: 10.1177/1591019920925677] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion has been shown to significantly improve outcomes. However, despite efficient rates of recanalization (60-90%), the rates of functional independence remain suboptimal (14-58%), most likely due to pathways of cell death in the brain that have already committed despite successful reperfusion. Pharmacologic neuroprotection provides a potential means of preventing this inevitable damage through targeting excitotoxicity, reactive oxygen species, cellular apoptosis, and inflammation. Numerous clinical trials using various neuroprotective agents have failed, but the majority of these trials did not include endovascular reperfusion, and thus the drugs were not reaching the therapeutic target. Intra-arterial delivery of neuroprotective agents via the guide catheter already in place for mechanical thrombectomy could provide a way to deliver high doses directly to the affected territory while limiting systemic exposure. Agents that have shown promise via the intra-arterial route in preclinical as well as some clinical models include magnesium sulfate, verapamil, cold saline, stem cells, and various combined approaches. Targeted hypothermia, achieved with intra-carotid infusion of cold saline, may provide an effective means of achieving hypothermia of the ischemic tissue while avoiding the systemic effects that have limited its use previously. Combination therapy of targeted hypothermia and a cocktail of drugs that provide anti-excitotoxic, anti-oxidant, anti-apopototic, and anti-inflammatory effects may provide an ideal approach that deserves further study in clinical trials.
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Affiliation(s)
- Thomas W Link
- Department of Neurosurgery, Weill Cornell Medical Institution New York Presbyterian Hospital, New York, NY, USA
| | - Alejandro Santillan
- Department of Neurosurgery, Weill Cornell Medical Institution New York Presbyterian Hospital, New York, NY, USA
| | - Athos Patsalides
- Department of Neurology, Weill Cornell Medical Institution New York Presbyterian Hospital, New York, NY, USA
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Abstract
Lipiodol is an iodinated poppy seed oil first synthesized in 1901. Originally developed for therapeutic purposes, it has mainly become a diagnostic contrast medium since the 1920s. At the end of the 20th century, Lipiodol underwent a transition back to a therapeutic agent, as exemplified by its increasing use in lymphangiography and lymphatic interventions. Nowadays, indications for lymphangiography include chylothorax, chylous ascites, chyluria, and peripheral lymphatic fistula or lymphoceles. In these indications, Lipiodol alone has a therapeutic effect with clinical success in 51% to 100% of cases. The 2 main access sites to the lymphatic system for lymphangiography are cannulation of lymphatic vessels in the foot (transpedal) and direct puncture of (mainly inguinal) lymph nodes (transnodal). In case of failure of lymphangiography alone to occlude the leaking lymphatic vessel as well as in indications such as protein-losing enteropathy, postoperative hepatic lymphorrhea, or plastic bronchitis, lymphatic vessels can also be embolized directly by injecting a mixture of Lipiodol and surgical glues (most commonly in thoracic duct embolization). The aim of this article is to review the historical role of Lipiodol and the evolution of its clinical application in lymphangiography over time until the current state-of-the-art lymphatic imaging techniques and interventions.
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Abou-Alfa GK, Jarnagin W, El Dika I, D'Angelica M, Lowery M, Brown K, Ludwig E, Kemeny N, Covey A, Crane CH, Harding J, Shia J, O'Reilly EM. Liver and Bile Duct Cancer. ABELOFF'S CLINICAL ONCOLOGY 2020:1314-1341.e11. [DOI: 10.1016/b978-0-323-47674-4.00077-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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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: 34] [Impact Index Per Article: 5.7] [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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Ahnfelt E, Degerstedt O, Lilienberg E, Sjögren E, Hansson P, Lennernäs H. Lipiodol-based emulsions used for transarterial chemoembolization and drug delivery: Effects of composition on stability and product quality. J Drug Deliv Sci Technol 2019. [DOI: 10.1016/j.jddst.2019.101143] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Masada T, Tanaka T, Nishiofuku H, Fukuoka Y, Taiji R, Sato T, Tatsumoto S, Minamiguchi K, Marugami N, Kichikawa K. Use of a Glass Membrane Pumping Emulsification Device Improves Systemic and Tumor Pharmacokinetics in Rabbit VX2 Liver Tumor in Transarterial Chemoembolization. J Vasc Interv Radiol 2019; 31:347-351. [PMID: 31542274 DOI: 10.1016/j.jvir.2019.06.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/17/2019] [Accepted: 06/18/2019] [Indexed: 11/19/2022] Open
Abstract
PURPOSE To evaluate the phamacokinetics of epirubicin in conventional transarterial chemoembolization using a developed pumping emulsification device with a microporous glass membrane in VX2 rabbits. MATERIALS AND METHODS Epirubicin solution (10 mg/mL) was mixed with ethiodized oil (1:2 ratio) using the device or 3-way stopcock. Forty-eight rabbits with VX2 liver tumor implanted 2 weeks prior to transarterial chemoembolization were divided into 2 groups: a device group (n = 24) and a 3-way-stopcock group (n = 24). Next, 0.5 mL of emulsion was injected into the hepatic artery, followed by embolization using 100-300-μm microspheres. The serum epirubicin concentrations (immediately after, 5 minutes after, and 10 minutes after) and the tumor epirubicin concentrations (20 minutes after and 48 hours after) were measured after transarterial chemoembolization. Histopathologic evaluation was performed with a fluorescence microscope. RESULTS The area under the curve and maximum concentrations of epirubicin in plasma were 0.45 ± 0.18 μg min/mL and 0.13 ± 0.06 μg/mL, respectively, in the device group and 0.71 ± 0.45 μg min/mL and 0.22 ± 0.17 μg/mL, respectively, in the 3-way-stopcock group (P = .013 and P = .021, respectively). The mean epirubicin concentrations in VX2 tumors at 48 hours in the device group and the 3-way-stopcock group were 13.7 ± 6.71 and 7.72 ± 3.26 μg/g tissue, respectively (P = .013). The tumor necrosis ratios at 48 hours were 62 ± 11% in the device group and 51 ± 13% in the 3-way-stopcock group (P = .039). CONCLUSIONS Conventional transarterial chemoembolization using the pumping emulsification device significantly improved the pharmacokinetics of epirubicin compared to the current standard technique using a 3-way stopcock.
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Affiliation(s)
- Tetsuya Masada
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan
| | - Toshihiro Tanaka
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan.
| | - Hideyuki Nishiofuku
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan
| | - Yasushi Fukuoka
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan
| | - Ryosuke Taiji
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan
| | - Takeshi Sato
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan
| | - Shota Tatsumoto
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan
| | - Kiyoyuki Minamiguchi
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan
| | - Nagaaki Marugami
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan
| | - Kimihiko Kichikawa
- Department of Radiology, Nara Medical University, 840 Shijo-ch, Kashihara, 634-8522, Japan
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Craig P, Young S, Golzarian J. Current Trends in the Treatment of Hepatocellular Carcinoma with Transarterial Embolization: Variability in Technical Aspects. Cardiovasc Intervent Radiol 2019; 42:1322-1328. [PMID: 31087146 DOI: 10.1007/s00270-019-02232-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 04/22/2019] [Indexed: 12/14/2022]
Abstract
PURPOSE While transarterial chemoembolization (TACE) is a mainstay of treatment for unresectable hepatocellular carcinomas (HCCs), technical aspects have varied considerably in the literature. These variations lead to heterogeneity and make meaningful comparisons between articles difficult. The goal of this survey was to report international embolization practices for the treatment of HCC in an effort to understand current treatment strategies as a first step toward technique standardization. MATERIALS AND METHODS An anonymous 18 question online survey, evaluating technical aspects of TACE, was distributed via e-mail to practicing members of the five largest interventional radiology societies in Chinese and English. A total of 1160 responses were obtained from 62 countries. RESULTS Between regions, there were significant statistical differences in nearly all responses, including the amount of ethiodol oil used for cTACE (p = < 0.001). Practitioners most commonly used greater than 7.5 ml of ethiodol oil (240/506, 47.4%) and most did not utilize a specific mixing method (249/505, 49.3%). Particles utilized varied by geographical region (p = < 0.001), spherical embolic particles were slightly favored (363/757, 47.9%), followed closely by gelatin-based or sponge particles (279/680, 36.8%). Gelfoam was used almost exclusively in Japan and Korea (79/82 responses). LC/DC beads were the most commonly used drug-eluting bead (DEB) (450/742, 60.6%), with the most common size of DEB being 100-300 μm (354/690, 51.3%, p = 0.07). CONCLUSION Technical aspects of transarterial embolization for HCC vary significantly by geographical location.
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Affiliation(s)
- Paul Craig
- University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
| | - Shamar Young
- University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA
| | - Jafar Golzarian
- University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA
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Interventional Radiologic Therapies for Hepatocellular Carcinoma: From Where We Began to Where We Are Going. MOLECULAR AND TRANSLATIONAL MEDICINE 2019. [DOI: 10.1007/978-3-030-21540-8_9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Poliektov N, Johnson DT. Treatment of Liver Tumors with Transarterial Chemoembolization. Semin Intervent Radiol 2018; 35:350-355. [PMID: 30402018 DOI: 10.1055/s-0038-1673423] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- Natalie Poliektov
- Department of Radiology, University of Colorado College of Medicine, Aurora, Colorado
| | - D Thor Johnson
- Department of Radiology, University of Colorado College of Medicine, Aurora, Colorado
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Dubbelboer IR, Sjögren E, Lennernäs H. Porcine and Human In Vivo Simulations for Doxorubicin-Containing Formulations Used in Locoregional Hepatocellular Carcinoma Treatment. AAPS JOURNAL 2018; 20:96. [PMID: 30167825 DOI: 10.1208/s12248-018-0251-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 07/31/2018] [Indexed: 12/21/2022]
Abstract
It is important to be able to simulate and predict formulation effects on the pharmacokinetics of a drug in order to optimize effectivity in clinical practice and drug development. Two formulations containing doxorubicin are used in the treatment of hepatocellular carcinoma (HCC): a Lipiodol-based emulsion (LIPDOX) and a loadable microbead system (DEBDOX). Although equally effective, the formulations are vastly different, and little is known about the parameters affecting doxorubicin release in vivo. However, mathematical modeling can be used to predict doxorubicin release properties from these formulations and its in vivo pharmacokinetic (PK) profiles. A porcine semi-physiologically based pharmacokinetic (PBPK) model was scaled to a human physiologically based biopharmaceutical (PBBP) model that was altered to include HCC. DOX in vitro and in vivo release data from LIPDOX or DEBDOX were collected from the literature and combined with these in silico models. The simulated pharmacokinetic profiles were then compared with observed porcine and human HCC patient data. DOX pharmacokinetic profiles of LIPDOX-treated HCC patients were best predicted from release data sets acquired by in vitro methods that did not use a diffusion barrier. For the DEBDOX group, the best predictions were from the in vitro release method with a low ion concentration and a reduced loading dose. The in silico modeling combined with historical release data was effective in predicting in vivo plasma exposure. This can give useful insights into the release method properties necessary for correct in vivo predictions of pharmacokinetic profiles of HCC patients dosed with LIPDOX or DEBDOX.
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Affiliation(s)
- Ilse R Dubbelboer
- Department of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden
| | - Erik Sjögren
- Department of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden
| | - Hans Lennernäs
- Department of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden.
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27
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Abd El-Moneim OM, Abd El-Rahim AH, Hafiz NA. Evaluation of selenium nanoparticles and doxorubicin effect against hepatocellular carcinoma rat model cytogenetic toxicity and DNA damage. Toxicol Rep 2018; 5:771-776. [PMID: 30094191 PMCID: PMC6071579 DOI: 10.1016/j.toxrep.2018.07.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 06/29/2018] [Accepted: 07/24/2018] [Indexed: 02/07/2023] Open
Abstract
The present study aimed to demonstrate the potent role of nanoselenium and Doxorubicin in retrogression of genotoxicity induced in hepatocellular carcinoma rat model by studying chromosomal aberration, micronuclei formation, DNA fragmentation as well as comet assay. Male rats hepatocellular carcinoma model were treated with Se-Nanoparticles, Doxurobicin (DOX) and the combination of both. The results revealed the protective effect of nanoselenium, Doxorubicin and their combination on bone marrow cytogenetic toxicity by decreasing chromosomal aberrations and micronuclei formation as well as their effects on rat's liver by decreasing DNA damage. Nevertheless, the treatment with nanoselenium either alone or in combination with Doxorubicin was more effective than treatment with doxorubicin alone.
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Affiliation(s)
- Omaima M. Abd El-Moneim
- Cell Biology Department, National Research Centre, El Tahrir Street, 12622, Dokki, Giza, Egypt
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28
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He MK, Zou RH, Wei W, Shen JX, Zhao M, Zhang YF, Lin XJ, Zhang YJ, Guo RP, Shi M. Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial. J Vasc Interv Radiol 2018; 29:1068-1077.e2. [PMID: 30042075 DOI: 10.1016/j.jvir.2018.03.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 03/21/2018] [Accepted: 03/23/2018] [Indexed: 01/13/2023] Open
Abstract
PURPOSE To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. RESULTS In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). CONCLUSIONS Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.
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Affiliation(s)
- Min-Ke He
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Ru-Hai Zou
- Department of Ultrasonography, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Wei Wei
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Jing-Xian Shen
- Department of Radiology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Ming Zhao
- Minimally Invasive Interventional Division, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Yong-Fa Zhang
- Department of Liver Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China
| | - Xiao-Jun Lin
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Yao-Jun Zhang
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Rong-Ping Guo
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Ming Shi
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China.
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29
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Kis B, El-Haddad G, Sheth RA, Parikh NS, Ganguli S, Shyn PB, Choi J, Brown KT. Liver-Directed Therapies for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control 2018; 24:1073274817729244. [PMID: 28975829 PMCID: PMC5937250 DOI: 10.1177/1073274817729244] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC) are primary liver cancers where all or most of the tumor burden is usually confined to the liver. Therefore, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease with minimal systemic side effects. The English medical literature and clinical trials were reviewed to provide a synopsis on the available liver-directed percutaneous therapies for HCC and IHC. Locoregional liver-directed therapies provide survival benefit for patients with HCC and IHC compared to best medical treatment and have lower comorbid risks compared to surgical resection. These treatment options should be considered, especially in patients with unresectable disease.
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Affiliation(s)
- Bela Kis
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Ghassan El-Haddad
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Rahul A Sheth
- 2 Department of Interventional Radiology, MD Anderson Cancer Center, Houston, TX, USA
| | - Nainesh S Parikh
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Suvranu Ganguli
- 3 Center for Image Guided Cancer Therapy, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Paul B Shyn
- 4 Department of Radiology, Abdominal Imaging and Intervention, Brigham and Women's, Boston, MA, USA
| | - Junsung Choi
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Karen T Brown
- 5 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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30
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Lungren MP, Towbin AJ, Roebuck DJ, Monroe EJ, Gill AE, Thakor A, Towbin RB, Cahill AM, Matthew Hawkins C. Role of interventional radiology in managing pediatric liver tumors : Part 1: Endovascular interventions. Pediatr Radiol 2018; 48:555-564. [PMID: 29362840 DOI: 10.1007/s00247-018-4068-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 12/02/2017] [Accepted: 01/03/2018] [Indexed: 12/14/2022]
Abstract
Primary liver malignancies are rare in children. Hepatoblastoma and hepatocellular carcinoma (HCC) together represent the overwhelming majority of cases. Overall survival of hepatoblastoma approaches 80% with multimodal treatment approaches that include chemotherapy, surgery and transplantation. However, there remains a subset of children with hepatoblastoma in whom resection or transplantation is not possible. The 5-year survival for children diagnosed with HCC is less than 30% and remains a significant therapeutic challenge. The poor outcomes for children with primary liver tumors motivate investigation of new therapeutic alternatives. Interventional oncology offers a broad scope of percutaneous and transcatheter endovascular cancer therapies that might provide clinical benefits. Minimally invasive approaches are distinct from medical, surgical and radiation oncologic treatments, and in adults these approaches have been established as the fourth pillar of cancer care. Transarterial chemoembolization is a minimally invasive locoregional treatment option performed by interventional radiologists with level-I evidence as standard of care in adults with advanced liver malignancy; transarterial chemoembolization in adults has served to prolong disease-free progression, downstage and bridge patients for surgical and transplant interventions, and improve overall survival. However, while several groups have reported that transarterial chemoembolization is feasible in children, the published experience is limited primarily to small retrospective case series. The lack of prospective trial evidence has in part limited the utilization of transarterial chemoembolization in the pediatric patient population. The purpose of this article is to provide an overview of the role of interventional radiology in the diagnosis and endovascular management of hepatic malignancies in children.
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Affiliation(s)
- Matthew P Lungren
- Department of Radiology, Lucile Packard Children's Hospital, Stanford University School of Medicine, 725 Welch Road Room 1862, Stanford, CA, 94305-5913, USA.
| | - Alexander J Towbin
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Derek J Roebuck
- Department of Radiology, Great Ormond Street Hospital, London, UK
| | - Eric J Monroe
- Department of Radiology, Division of Interventional Radiology, Seattle Children's Hospital, Seattle, WA, USA
| | - Anne E Gill
- Department of Radiology and Imaging Sciences, Division of Interventional Radiology and Image-guided Medicine, Emory University School of Medicine, Atlanta, GA, USA.,Department of Radiology and Imaging Sciences, Division of Pediatric Radiology, Emory University School of Medicine, Children's Healthcare of Atlanta at Egleston, Atlanta, GA, USA
| | - Avnesh Thakor
- Department of Radiology, Lucile Packard Children's Hospital, Stanford University School of Medicine, 725 Welch Road Room 1862, Stanford, CA, 94305-5913, USA
| | - Richard B Towbin
- Department of Radiology, Phoenix Children's Hospital, Phoenix, AZ, USA
| | - Anne Marie Cahill
- Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - C Matthew Hawkins
- Department of Radiology and Imaging Sciences, Division of Interventional Radiology and Image-guided Medicine, Emory University School of Medicine, Atlanta, GA, USA.,Department of Radiology and Imaging Sciences, Division of Pediatric Radiology, Emory University School of Medicine, Children's Healthcare of Atlanta at Egleston, Atlanta, GA, USA
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31
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Zhao M, Xiang P, Jiang H. TransArterial ChemoEmbolization (TACE) with platinum versus anthracyclines for hepatocellular carcinoma: A meta-analysis. Int J Surg 2018; 53:151-158. [PMID: 29602011 DOI: 10.1016/j.ijsu.2018.03.049] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Revised: 03/17/2018] [Accepted: 03/21/2018] [Indexed: 01/27/2023]
Abstract
OBJECTIVE To determine the clinical efficacy of TACE with platinum versus anthracyclines for hepatocellular carcinoma (HCC) patients using a meta-analysis. METHODS We conducted a systematic review of the literature in PubMed, Embase, and the Cochrane Library database to discover relevant randomized controlled trials (RCTs) and observational studies. Data on therapeutic response, adverse event and overall survival rate from studies that compared TACE with platinum versus anthracyclines for HCC patients was extracted for pooled estimation. Subgroup analysis was used if further investigation was needed. The Q statistic and the I2 index statistic were used to assess heterogeneity. Publication bias was evaluated using Egger's test. RESULTS Four RCTs and seven observational studies containing 1405 patients were included in this meta-analysis. After comparing RCTs and observational studies separately, the pooled estimation results indicated that no significant difference existed between platinum and anthracyclines regarding therapeutic response, adverse event and overall survival rate. Furthermore, Egger's test revealed bias in pooled estimation of survival rate among RCTs. CONCLUSIONS Based on current results, we concluded that TACE with platinum revealed similar clinical efficacy compared with anthracyclines. And more relative studies in this field were expected in the future.
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Affiliation(s)
- Mengdie Zhao
- Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, PR China
| | - Ping Xiang
- Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, PR China
| | - Hao Jiang
- Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, PR China.
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32
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Tanaka T, Masada T, Nishiofuku H, Fukuoka Y, Sato T, Tatsumoto S, Marugami N, Higashi S, Kichikawa K. Development of pumping emulsification device with glass membrane to form ideal lipiodol emulsion in transarterial chemoembolization. Eur Radiol 2017; 28:2203-2207. [PMID: 29247350 DOI: 10.1007/s00330-017-5197-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 10/31/2017] [Accepted: 11/16/2017] [Indexed: 11/30/2022]
Abstract
PURPOSE To evaluate a pumping emulsification device that can improve the physiochemical properties and stability of lipiodol emulsion for conventional transarterial chemoembolization. MATERIALS AND METHODS A pumping emulsification device constructed of a glass membrane with a hydrophobic surface with pore size of 50 μm in diameter was placed between two syringe adaptors. Epirubicin solutions were mixed with lipiodol with pumping exchanges using the emulsification device or a three-way cock. The ratios of epirubicin solution to lipiodol were 1:2 or 1:1. A total of 120 emulsions were created. RESULTS The emulsification device showed significantly higher percentages of water-in-oil when compared with the three-way cock (97.9 % vs. 68.9 % in 1:2 ratio, and 82.1 % vs. 17.8 % in 1:1 ratio, p < .001). Droplet sizes in the emulsification device were more homogenous. Mean droplet sizes and viscosities in the emulsification device did not show any significant changes for 30 min after pumping, whereas in the three-way cock, the droplet sizes significantly enlarged and viscosities significantly decreased (p=.023 and p=.002). CONCLUSION The emulsification device can form a high percentage of water-in-oil emulsion with stable droplets sizes and viscosities. This developed device is promising to increase therapeutic effects in conventional transarterial chemoembolization. KEY POINTS • We developed new device for transarterial chemoembolization for liver cancer. • The device can improve the physiochemical properties of lipiodol emulsion. • The device can increase the therapeutic effects in conventional transarterial chemoembolization.
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Affiliation(s)
- Toshihiro Tanaka
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan.
| | - Tetsuya Masada
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan
| | - Hideyuki Nishiofuku
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan
| | - Yasushi Fukuoka
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan
| | - Takeshi Sato
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan
| | - Shota Tatsumoto
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan
| | - Nagaaki Marugami
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan
| | | | - Kimihiko Kichikawa
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan
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33
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Liu K, Zhang X, Xu W, Chen J, Yu J, Gamble JR, McCaughan GW. Targeting the vasculature in hepatocellular carcinoma treatment: Starving versus normalizing blood supply. Clin Transl Gastroenterol 2017; 8:e98. [PMID: 28617447 PMCID: PMC5518951 DOI: 10.1038/ctg.2017.28] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 04/19/2017] [Indexed: 12/13/2022] Open
Abstract
Traditional treatments for intermediate or advanced stage hepatocellular carcinoma (HCC) such as transarterial chemoembolization (TACE) and anti-angiogenesis therapies were developed to starve tumor blood supply. A new approach of normalizing structurally and functionally abnormal tumor vasculature is emerging. While TACE improves survival in selected patients, the resulting tumor hypoxia stimulates proliferation, angiogenesis, treatment resistance and metastasis, which limits its overall efficacy. Vessel normalization decreases hypoxia and improves anti-tumor immune infiltrate and drug delivery. Several pre-clinical agents aimed at normalizing tumor vasculature in HCC appear promising. Although anti-angiogenic agents with vessel normalizing potential have been trialed in advanced HCC with modest results, to date their primary intention had been to starve the tumor. Judicious use of anti-angiogenic therapies is required to achieve vessel normalization yet avoid excessive pruning of vessels. This balance, termed the normalization window, is yet uncharacterized in HCC. However, the optimal class, dose and schedule of vascular normalization agents, alone or in combination with other therapies needs to be explored further.
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Affiliation(s)
- Ken Liu
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.,Centenary Institute and AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Xiang Zhang
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Weiqi Xu
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Jinbiao Chen
- Centenary Institute and AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Jun Yu
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Jennifer R Gamble
- Centre for the Endothelium, Vascular Biology Program, Centenary Institute, and University of Sydney, Sydney, New South Wales, Australia
| | - Geoffrey W McCaughan
- Centenary Institute and AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, New South Wales, Australia
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34
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Traitements intra-artériels des carcinomes hépatocellulaires : évidence clinique et perspectives à venir. ONCOLOGIE 2017. [DOI: 10.1007/s10269-017-2711-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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35
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Masada T, Tanaka T, Nishiofuku H, Fukuoka Y, Sato T, Tatsumoto S, Marugami N, Kichikawa K. Techniques to Form a Suitable Lipiodol-Epirubicin Emulsion by Using 3-Way Stopcock Methods in Transarterial Chemoembolization for Liver Tumor. J Vasc Interv Radiol 2017; 28:1461-1466. [PMID: 28501268 DOI: 10.1016/j.jvir.2017.03.032] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 03/22/2017] [Accepted: 03/22/2017] [Indexed: 11/26/2022] Open
Abstract
PURPOSE To compare physicochemical properties of emulsions of ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and epirubicin prepared using different techniques for conventional transarterial chemoembolization. MATERIALS AND METHODS Lipiodol was mixed with epirubicin solution (8.33 mg/mL) by using a 3-way stopcock. The following technical parameters were compared: ratio of epirubicin solution to Lipiodol (1:2 vs 1:1), number of pumping exchanges through the stopcock (20 exchanges vs 10 exchanges), pumping speed (1 s/push vs 2 s/push), and first push syringe (epirubicin solution vs Lipiodol). RESULTS The mean percentage of water-in-oil was 70.45 ± 1.51 in the 1:2 epirubicin-Lipiodol ratio and 16.03 ± 2.95 in the 1:1 ratio (P < .001). The first push syringe did not influence emulsion type. Median droplet sizes were significantly larger in the slower pumping speed (52.0 μm in 2 s vs 33.7 μm in 1 s; P < .001), whereas there was no significant difference in number of pumping exchanges. Droplet sizes enlarged during 30 minutes after pumping. Viscosity was lower in the 1:1 ratio and the slower pumping speed. Viscosity decreased during 30 minutes after pumping. CONCLUSIONS The ratio of epirubicin to Lipiodol is a significant factor to form water-in-oil emulsions with higher viscosity. The percentage of water-in-oil is limited to 70% using current pumping techniques. The pumping speed strongly influences droplet size and viscosity.
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Affiliation(s)
- Tetsuya Masada
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
| | - Toshihiro Tanaka
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
| | - Hideyuki Nishiofuku
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
| | - Yasushi Fukuoka
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
| | - Takeshi Sato
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
| | - Shota Tatsumoto
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
| | - Nagaaki Marugami
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
| | - Kimihiko Kichikawa
- Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan
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36
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Zhao H, Liu F, Yue Z, Wang L, Fan Z, He F. Association of hepatic vein Lipiodol tram-track sign during transcatheter arterial chemoembolization with perioperative death. J Int Med Res 2017; 45:1148-1157. [PMID: 28425822 PMCID: PMC5536422 DOI: 10.1177/0300060517704141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective To assess the relationship between the hepatic vein Lipiodol tram-track sign during transcatheter arterial chemoembolization (TACE) and perioperative death. Methods Patients treated for hepatic carcinoma at the Beijing Shijitan Hospital, Capital Medical University from January 2010 to December 2015 were retrospectively evaluated. The patients underwent hepatic TACE with Lipiodol. The incidence of the hepatic vein Lipiodol tram-track sign, prognosis, and possible risk factors were analyzed. Results A total of 5372 patients underwent hepatic TACE and had complete available intraoperative imaging data. Among them, nine patients showed the hepatic vein Lipiodol tram-track sign, including five who died intraoperatively. The patients who died had liver metastasis from hepatocellular carcinoma, cholangiocarcinoma, or breast cancer and had previously received doxorubicin. The survivors had metastasis from gastric or colorectal cancer and had not received doxorubicin. Conclusion Occurrence of the hepatic vein Lipiodol tram-track sign during hepatic TACE is likely to result in perioperative death.
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Affiliation(s)
- Hongwei Zhao
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Fuquan Liu
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Zhendong Yue
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Lei Wang
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Zhenhua Fan
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Fuliang He
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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37
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Kim JW, Lee CH, Park YS, Seo TS, Song MG, Kim JH, Kim KA, Park CM. The value of paradoxical uptake of hepatocellular carcinoma on the hepatobiliary phase of gadoxetic acid-enhanced liver magnetic resonance imaging for the prediction of lipiodol uptake after transcatheter arterial chemoembolization. Eur J Radiol 2017; 89:169-176. [PMID: 28267535 DOI: 10.1016/j.ejrad.2017.02.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Revised: 12/24/2016] [Accepted: 02/03/2017] [Indexed: 11/26/2022]
Abstract
PURPOSE To compare the response to transcatheter arterial chemoembolization (TACE) between hepatocellular carcinoma (HCC) with paradoxical uptake on the hepatobiliary phase (HBP) (HCCpara) and HCC with defect on the HBP (HCCdef), and to identify some imaging features that can differentiate between two groups. MATERIALS AND METHODS Ninety-three HCCs from 54 patients who underwent gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) prior to TACE were included. HCCs were classified into two groups according to the signal intensity (SI) on the HBP: HCCpara and HCCdef. Using post-TACE computed tomography (CT) as a reference standard, initial compact lipiodol uptake was assessed and compared between groups. The arterial enhancement ratio (AER), SI ratios of the arterial phase and HBP, and presence of the capsule appearance were compared between groups. After initial response, local tumor recurrence within 6 and 18 months was evaluated based on follow-up CT or MRI. RESULTS Fifteen HCCpara and 78 HCCdef were included. Compared to HCCdef, HCCpara showed more frequent initial compact lipiodol uptake (p=0.009), larger mean size (p=0.019), lower AER (p=0.005), higher SI ratio of the HBP (p<0.0001), and more frequent capsule appearance (p<0.0001). Local tumor recurrence rate within 6 months was also significantly lower in HCCpara than in HCCdef (p=0.008). CONCLUSION Despite larger size and lower AER, HCCpara showed more frequent initial compact lipiodol uptake and lower early local recurrence rate after TACE than did HCCdef.
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Affiliation(s)
- Jeong Woo Kim
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
| | - Chang Hee Lee
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
| | - Yang Shin Park
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
| | - Tae Seok Seo
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
| | - Myung Gyu Song
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
| | - Kyeong Ah Kim
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
| | - Cheol Min Park
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
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Dasse KD, Lander MJ, Novelli PM. Chemoembolization With Drug-Eluting Beads for the Treatment of Hepatocellular Carcinoma. J Adv Pract Oncol 2016; 7:764-778. [PMID: 29670812 PMCID: PMC5902156 DOI: 10.6004/jadpro.2016.7.7.8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Kathy Diener Dasse
- Department of Pharmacy Services, University of Michigan Health Systems, Ann Arbor, Michigan
| | - Michael J Lander
- Pharmacy Services, Mayo Clinic - St. Mary's Hospital, Rochester, Minnesota
| | - Paula M Novelli
- Division of Vascular and Interventional Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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Lanza E, Donadon M, Poretti D, Pedicini V, Tramarin M, Roncalli M, Rhee H, Park YN, Torzilli G. Transarterial Therapies for Hepatocellular Carcinoma. Liver Cancer 2016; 6:27-33. [PMID: 27995085 PMCID: PMC5159740 DOI: 10.1159/000449347] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The treatment of hepatocellular carcinoma (HCC) is still a major health issue because of its increasing incidence and because of the complexity of its management. Transarterial embolization (TAE) and transarterial chemoembolization (TACE) are two widely used locoregional therapies in the treatment of HCC, especially for unresectable intermediate and advanced HCCs. SUMMARY The modern use of TAE and TACE opens new scenarios for the treatment of unresectable HCC and has yielded interesting results. The present work describes the role of transarterial therapies for HCC and focuses on the different Western and Eastern approaches to the study of response predictors. KEY MESSAGES Recent refinements in interventional radiology techniques and in HCC patient selection have facilitated better local control of the disease. The molecular profiling of HCC to predict the response to TACE and TAE will greatly help clinicians identify the optimum therapy.
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Affiliation(s)
- Ezio Lanza
- Department of Interventional Radiology, Humanitas University, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Matteo Donadon
- Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Dario Poretti
- Department of Interventional Radiology, Humanitas University, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Vittorio Pedicini
- Department of Interventional Radiology, Humanitas University, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Marco Tramarin
- Department of Interventional Radiology, Humanitas University, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Massimo Roncalli
- Department of Pathology, Humanitas University, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Hyungjin Rhee
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Young Nyun Park
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Guido Torzilli
- Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Research Hospital IRCCS, Milan, Italy,*Guido Torzilli, MD, PhD Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Research Hospital IRCCS, Via Manzoni, 56, IT–20089 Rozzano, Milano (Italy), Tel. +39 02 8224 4502, E-Mail:
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Ogawa C, Minami Y, Morita M, Noda T, Arasawa S, Izuta M, Kubo A, Matsunaka T, Tamaki H, Shibatoge M, Kudo M. Prediction of Embolization Area after Conventional Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Using SYNAPSE VINCENT. Dig Dis 2016; 34:696-701. [PMID: 27750240 DOI: 10.1159/000448859] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
PURPOSE Transcatheter arterial chemoembolization (TACE) is one of the most effective therapeutic options for hepatocellular carcinoma (HCC) and it is important to protect residual liver function after treatment as well as the effect. To reduce the liver function deterioration, we evaluated the automatic software to predict the embolization area of TACE in 3 dimensions. MATERIALS AND METHODS Automatic prediction software of embolization area was used in chemoembolization of 7 HCCs. Embolization area of chemoembolization was evaluated within 1 week CT findings after TACE and compared simulated area using automatic prediction software. RESULTS The maximal diameter of these tumors is in the range 12-42 mm (24.6 ± 9.5 mm). The average time for detecting tumor-feeding branches was 242 s. The total time to detect tumor-feeding branches and simulate the embolization area was 384 s. All cases could detect all tumor-feeding branches of HCC, and the expected embolization area of simulation with automatic prediction software was almost the same as the actual areas, as shown by CT after TACE. CONCLUSION This new technology has possibilities to reduce the amount of contrast medium used, protect kidney function, decrease radiation exposure, and improve the therapeutic effect of TACE.
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Yamashita Y, Yoshimatsu S, Sumi M, Harada M, Takahashi M. Dynamic MR Imaging of Hepatoma Treated by Transcatheter Arterial Embolization Therapy. Acta Radiol 2016. [DOI: 10.1177/028418519303400319] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The effect of transcatheter arterial chemo-embolization therapy (TACE) for hepatoma was evaluated with dynamic MR imaging with Gd-DTPA in 37 patients (44 tumors). TACE was performed using Lipiodol/cis-platinum and gelatin sponge (or microspheres) as an embolic material. All patients were examined with dynamic CT and MR imaging before and after treatment. On conventional spin echo images, changes of signal intensity after treatment varied regardless of presence of Lipiodol. Dynamic MR imaging revealed changes of tumor vascularity before and after treatment. On histologic correlation, areas of persistent tumor enhancement on dynamic MR imaging corresponded to areas of viable tumor cells while areas of nonenhancement corresponded to areas of necrosis. Dynamic MR imaging was superior in contrast resolution and was not influenced by the presence of Lipiodol compared with dynamic CT, and therefore residual viable tumors were better defined by dynamic MR imaging.
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Okazaki M, Higashihara H, Ono H, Koganemaru F, Fujimitsu R, Mizuma Y, Nakamura T, Sato S, Kimura S, Kodama S. Chemoembolization for Hepatocellular Carcinoma via the Inferior Pancreaticoduodenal Artery in Patients with Celiac Artery Stenosis. Acta Radiol 2016. [DOI: 10.1177/028418519303400105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Twenty-one patients with hepatocellular carcinoma (HCC) accompanied by extensive celiac artery stenosis or obstruction were treated by chemoembolization via the inferior pancreaticoduodenal artery (IPDA). The tip of the catheter was placed in the arteries in front of the confluence with the proper hepatic artery in 12 patients (group A: the proximal portion of the IPDA in 10, and common hepatic artery in 2), and in the proper hepatic artery or branches of it (group B) in 9 using a coaxial catheter system. Transient hyperamylasemia was observed in 10 of the 12 patients in group A and in 3 of the 9 patients in group B after chemoembolization. Splenic infarction developed in 8 patients in group A and in none in group B. Intrapancreatic fluid collection was present in 2 patients in group A following chemoembolization. No fatal complications were encountered. The 1-, 2-, and 3-year survival rates of the 10 patients in group A treated by only chemoembolization were 90, 57, and 23%, respectively (mean survival 780 days). The 1- and 2-year survival rates of 9 patients in group B were 85.8 and 85.8% (mean 879 days), respectively. Considering the severity of complications and the survival rates in groups A and B, chemoembolization by superselective catheterization into the hepatic artery via the IPDA is the treatment of choice. However, chemoembolization from the arteries in front of the confluence with the proper hepatic artery seems to be acceptable in cases of hypervascular HCC which fail to be superselectively catheterized.
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Abstract
Gastric complications may be a problem in transcatheter arterial chemoembolization, if the right gastric artery branches distally from the proper hepatic artery or its branch, or the accessory left gastric artery arises from the left hepatic artery. We occluded the proper hepatic artery with a balloon catheter to redirect blood flow in these gastric branches toward the liver. This procedure prevented chemoembolic agents from flowing into the gastric branches, and accordingly protected against gastric complications even when chemoembolization was performed by injecting the agents proximally to the gastric branches.
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Savastano S, Feltrin GP, Neri D, da Pian P, Chiesura-Corona M, Roman E, Battaglia G, Gerunda G, Lise M, Miotto D. Palliative Treatment of Hepatocellular Carcinoma with Transcatheter Arterial Embolization. Acta Radiol 2016. [DOI: 10.1177/028418519303400106] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Thirty-three consecutive patients with previously untreated hepatocellular carcinoma (HCC) and 6 patients with recurrent HCC were treated with transcatheter arterial embolization (TAE). The patients were not eligible for surgical resection or percutaneous ethanol injection. TAE was performed with Lipiodol Ultra-Fluid, epidoxorubicin and Gelfoam, with a mean of 1.7 treatments per patient. CT was performed 15 days after TAE. The mean cumulative survival was 14.2 months in patients with previously untreated HCC. The survival of patients stages Okuda I and II did not differ significantly (p > 0.05); tumor size did not affect survival (p > 0.05). Two patients with recurrent HCC died 7.0 and 9.3 months after the diagnosis of tumor recurrence; the remaining 4 patients are still alive with a maximum follow-up of 22.5 months from the diagnosis of HCC recurrence. Ten complications occurred in 8 patients, and were controlled by medical therapy. Eleven patients died during the study; no death was related to TAE. The series was not randomized, but comparison with the natural history of HCC suggests that TAE is effective as palliative treatment of advanced or recurrent HCC.
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Inoue H, Miyazono N, Hori A, Miyake S, Satake M, Kanetsuki I, Nishida H, Ikeda K, Nakajo M. Treatment of Hepatocellular Carcinoma by Intraarterial Injection of Adriamycin/Mitomycin C Oil Suspension (ADMOS) Alone or Combined with CIS-Diaminodichloroplatinum (CDDP). Acta Radiol 2016. [DOI: 10.1177/028418519303400416] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We evaluated the effects of intraarterial injection of Adriamycin/Mitomycin C oil (Lipiodol) suspension (ADMOS) alone and ADMOS + cis-diaminodichloroplatinum (CDDP) in 135 patients with hepatocellular carcinoma (HCC). A total of 59 patients received ADMOS alone and 76 patients received ADMOS + CDDP (ADMOS/CDDP). Tumor size was reduced by over 25% in 13 (34%) of the evaluable 38 patients in the ADMOS-alone group and in 39 (51%) of the 76 evaluable patients in the ADMOS/CDDP group. Serum alpha-fetoprotein (AFP) levels decreased by more than 50% in 10 (59%) of 17 ADMOS-alone patients and in 23 (70%) of 33 ADMOS/CDDP patients whose pretreatment AFP levels were above 0.2 mg/l. The overall one- and 2-year survival rates were 68% and 41%, respectively. No severe complications and no significant changes in laboratory values were observed, except for one patient in the ADMOS/CDDP group who developed a liver abscess. Although the tumor response was significantly better in patients treated by ADMOS/CDDP than in those treated by ADMOS-alone (p < 0.05), there was no significant difference in the survival rates between the 2 groups. The intraarterial injection of ADMOS and CDDP was concluded to be effective in treating HCC judging by tumor response.
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Murakami T, Nakamura H, Hori S, Tomoda K, Mitani T, Nakanishi K, Hashimoto T, Tsuda K, Kozuka T, Monden M, Wakasa K. Detection of Viable Tumor Cells in Hepatocellular Carcinoma following Transcatheter Arterial Chemoembolization with Iodized Oil. Acta Radiol 2016. [DOI: 10.1177/028418519303400419] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
To evaluate the effect of transcatheter arterial chemoembolization (TACE) with iodized oil for hepatocellular carcinoma (HCC), dynamic turbo-fast low angle shot (turbo-FLASH) (TR/TE/flip angle/TI, 8.5/4.6/10/200) MR imaging with gadopentetate dimeglumine was performed in 10 patients with HCC after TACE with iodized oil and before partial hepatectomy. Immediately after 0.05 mmol/kg b.w. of gadopentetate dimeglumine was administered intravenously, 10 images were obtained in the first 20 s (early phase). Then, one image every 30 s from 1 to 3 min (late phase), and images at 5 min and 7 min (delayed phase) were obtained serially. In the early phase, HCC showed no enhancement in 5 patients, partial hyperintense enhancement in 4, and total hyperintense enhancement in one. Viable regions of the tumor, evaluated at histopathology, showed hyperintense enhancement relative to the surrounding liver parenchyma in the early phase, while necrotic regions showed no enhancement. Both viable and necrotic regions showed lower signal intensities than the surrounding liver parenchyma in both late and delayed phases. By using dynamic turbo-FLASH MR imaging, we were able to accurately evaluate the effect of TACE with iodized oil for HCC in 8 of the 10 patients. In 2 patients, in whom small viable cells were seen in the HCC, viable regions could not be detected with our technique. It is concluded that turbo-FLASH dynamic MR imaging was useful for evaluating the effect of TACE for HCC.
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Treatment of Hepatocellular Carcinoma by Segmental Hepatic Artery Injection of Adriamycin-In-Oil Emulsion with Overflow to Segmental Portal Veins. Acta Radiol 2016. [DOI: 10.1177/028418519003100405] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Hepatocellular carcinoma was treated with slow injection of an emulsion containing 40 to 60 mg of adriamycin and 3.5 to 12 ml of Lipiodol into the portal vein via a segmental hepatic artery. During and after the injection, the portal branches of the segment were demonstrated. Six patients with resectable hepatocellular carcinoma received this treatment, which in 3 of them was followed by embolization with Gelfoam of the segmental artery. In these 3, all main tumors and daughter nodules became completely necrotic, but some infarction developed in the non-tumorous area. Those without Gelfoam had complete necrosis of all daughter nodules, but incomplete response of the main tumor. This combined treatment may be recommended for patients with localized lesions which are non-resectable due to cirrhosis, or for other reasons.
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Shima T, Mizuno M, Otsuji H, Mizuno C, Obata H, Park H, Nakajo S, Okanoue T. Evaluation of transcatheter arterial embolization therapy on hepatocellular carcinomas using contrast-enhanced harmonic power Doppler sonography: comparison with CT, power Doppler sonography, and dynamic MRI. J Med Ultrason (2001) 2016; 32:107-13. [PMID: 27277266 DOI: 10.1007/s10396-005-0045-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2005] [Accepted: 04/12/2005] [Indexed: 11/25/2022]
Abstract
PURPOSE The aim of this study was to assess and compare the sensitivity of power Doppler sonography, contrast-enhanced sonography, plain computed tomography (CT), and dynamic magnetic resonance imaging (MRI) for detecting hepatocellular carcinoma (HCC) nodules incompletely treated with transcatheter arterial embolization (TAE). METHODS A total of 63 unresectable HCC nodules were examined in this study. The HCCs were treated with TAE. All patients underwent plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI 1 week after TAE. The sensitivity of each modality to incompletely treated HCC nodules was compared. Detection of the residual viable HCC on angiography or tumor biopsy was regarded as the gold standard for the diagnosis of incomplete treatment. RESULTS Twenty-four nodules (38%) were diagnosed as incompletely treated. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these incompletely treated nodules were 42% (10/24), 46% (11/24), 88% (21/24), and 79% (19/24), respectively. Eighty percent (19 nodules) of the 24 incompletely treated nodules were located within a depth of less than 8 cm. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these superficial incompletely treated nodules were 37% (7/19), 53% (10/19), 100% (19/19), and 74% (14/19), respectively. In contrast, the sensitivities of each modality to deeply located nodules were 60% (3/5), 20% (1/5), 40% (2/5), and 100% (5/5), respectively. CONCLUSION Plain CT and power Doppler sonography had a low sensitivity to HCC nodules incompletely treated with TAE. Except for those that were deeply located, contrast-enhanced harmonic sonography showed the highest sensitivity in detecting incompletely treated HCC nodules.
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Affiliation(s)
- Toshihide Shima
- Departments of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita, Osaka, 564-0013, Japan.
| | - Masayuki Mizuno
- Departments of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita, Osaka, 564-0013, Japan
| | - Hideaki Otsuji
- Department of Radiology, Saiseikai Suita Hospital, Osaka, Japan
| | - Chiemi Mizuno
- Departments of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita, Osaka, 564-0013, Japan
| | - Hirozumi Obata
- Departments of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita, Osaka, 564-0013, Japan
| | - Hyohun Park
- Departments of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita, Osaka, 564-0013, Japan
| | - Shinobu Nakajo
- Departments of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita, Osaka, 564-0013, Japan
| | - Takeshi Okanoue
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Patsalides A, Yamada Y, Bilsky M, Lis E, Laufer I, Gobin YP. Spinal intraarterial chemotherapy: interim results of a Phase I clinical trial. J Neurosurg Spine 2015; 24:217-222. [PMID: 26496162 DOI: 10.3171/2015.5.spine14830] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECT Despite advances in therapies using radiation oncology and spinal oncological surgery, there is a subgroup of patients with spinal metastases who suffer from progressive or recurrent epidural disease and remain at risk for neurological compromise. In this paper the authors describe their initial experience with a novel therapeutic approach that consists of intraarterial (IA) infusion of chemotherapy to treat progressive spinal metastatic disease. METHODS The main inclusion criterion was the presence of progressive, metastatic epidural disease to the spine causing spinal canal compromise in patients who were not candidates for the standard treatments of radiation therapy and/or surgery. All tumor histological types were eligible for this trial. Using the transfemoral arterial approach and standard neurointerventional techniques, all patients were treated with IA infusion of melphalan in the arteries supplying the epidural tumor. The protocol allowed for up to 3 procedures repeated at 3- to 6-week intervals. Outcome measures included physiological measures: 1) periprocedural complications according to the National Cancer Institute's Common Terminology Criteria for Adverse Events; and 2) MRI to assess for tumor response. RESULTS Nine patients with progressive spinal metastatic disease and cord compression were enrolled in a Phase I clinical trial of selective IA chemotherapy. All patients had metastatic disease from solid organs and were not candidates for further radiation therapy or surgery. A total of 19 spinal intraarterial chemotherapy (SIAC) procedures were performed, and the follow-up period ranged from 1 to 7 months (median 3 months). There was 1 serious adverse event (febrile neutropenia). Local tumor control was seen in 8 of 9 patients, whereas tumor progression at the treated level was seen in 1 patient. CONCLUSIONS These preliminary results support the hypothesis that SIAC is feasible and safe.
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Affiliation(s)
- Athos Patsalides
- Interventional Neuroradiology, Department of Neurological Surgery, Weill Cornell Medical College; and
| | | | | | - Eric Lis
- Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - Yves Pierre Gobin
- Interventional Neuroradiology, Department of Neurological Surgery, Weill Cornell Medical College; and
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Development of Conventional Transarterial Chemoembolization for Hepatocellular Carcinomas in Japan: Historical, Strategic, and Technical Review. AJR Am J Roentgenol 2015; 205:764-73. [DOI: 10.2214/ajr.15.14825] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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