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Chang B, Zhou C, Liu C, Mu L, Huang M, Bai M. Clinical outcomes of modified transarterial chemoembolization vs. drug-eluting bead transarterial chemoembolization as initial treatment for single hepatocellular carcinoma: a propensity score matching analysis. Ann Med 2024; 56:2423787. [PMID: 39498531 PMCID: PMC11539394 DOI: 10.1080/07853890.2024.2423787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 06/10/2024] [Accepted: 09/30/2024] [Indexed: 11/07/2024] Open
Abstract
BACKGROUND & AIMS Optimizing transarterial chemoembolization (TACE) can enhance treatment efficacy for hepatocellular carcinoma (HCC). This study compares modified TACE (M-TACE), which combines a lipiodol-based emulsion and drug-eluting beads, with drug-eluting bead TACE (DEB-TACE) as initial therapies for solitary HCC. METHODS In this retrospective study, 185 patients undergoing M-TACE or DEB-TACE were evaluated. Propensity score matching was used to create 69 balanced pairs. Initial tumor response, repeated treatments within six months, local tumor progression (LTP), overall survival (OS), and adverse events (AEs) were assessed. RESULTS M-TACE exhibited significantly higher initial complete response (CR) rates (39.1% vs. 23.2%, p = 0.043) and fewer repeated treatments within six months (1.7 ± 0.9 vs. 2.1 ± 0.7; p = 0.033) compared to DEB-TACE. LTP rates were notably lower with M-TACE at 12 months (39.1% vs. 65.2%, p = 0.002), and median time to LTP was prolonged with M-TACE (13.3 vs. 8.2 months, p = 0.038). Stratified analysis revealed a significantly longer OS in individuals achieving a CR after the initial M-TACE (50.5 vs. 33.4 months, p = 0.043). However, the overall study population did not exhibit a significant difference in OS between the two groups. Comparable AEs (all p > 0.05) were observed. CONCLUSIONS M-TACE showed higher initial CR rates, lower LTP rates, and extended time to LTP compared to DEB-TACE, indicating its potential to enhance TACE effectiveness for solitary HCC.
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Affiliation(s)
- Boyang Chang
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Churen Zhou
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Chengcheng Liu
- Department of Hematology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Luwen Mu
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Mingsheng Huang
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Mingjun Bai
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
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Yuan G, Xu Y, Bai X, Wang W, Wu X, Chen J, Li J, Jia X, Gu Z, Zhang X, Hu W, Wang J, Liu Y, Zhu XM. Autophagy-Targeted Calcium Phosphate Nanoparticles Enable Transarterial Chemoembolization for Enhanced Cancer Therapy. ACS APPLIED MATERIALS & INTERFACES 2023; 15:11431-11443. [PMID: 36848495 DOI: 10.1021/acsami.2c18267] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Transarterial chemoembolization (TACE) is commonly used for treating advanced hepatocellular carcinoma (HCC). However, the instability of lipiodol-drug emulsion and the altered tumor microenvironment (TME, such as hypoxia-induced autophagy) postembolization are responsible for the unsatisfactory therapeutic outcomes. Herein, pH-responsive poly(acrylic acid)/calcium phosphate nanoparticles (PAA/CaP NPs) were synthesized and used as the carrier of epirubicin (EPI) to enhance the efficacy of TACE therapy through autophagy inhibition. PAA/CaP NPs have a high loading capacity of EPI and a sensitive drug release behavior under acidic conditions. Moreover, PAA/CaP NPs block autophagy through the dramatic increase of intracellular Ca2+ content, which synergistically enhances the toxicity of EPI. TACE with EPI-loaded PAA/CaP NPs dispersed in lipiodol shows an obvious enhanced therapeutic outcome compared to the treatment with EPI-lipiodol emulsion in an orthotopic rabbit liver cancer model. This study not only develops a new delivery system for TACE but also provides a promising strategy targeting autophagy inhibition to improve the therapeutic effect of TACE for the HCC treatment.
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Affiliation(s)
- Gang Yuan
- State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
- Department of Interventional Radiology, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou 646000, China
| | - Yanneng Xu
- State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
- Department of Interventional Radiology, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou 646000, China
| | - Xiaopeng Bai
- Department of Physics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR 999077, China
| | - Weiming Wang
- State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
- Department of General Surgery (Vascular Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Xuan Wu
- State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
| | - Jianli Chen
- State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
| | - Jie Li
- State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
| | - Xiaohui Jia
- State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
| | - Zeyun Gu
- State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
| | - Xun Zhang
- Department of Interventional Radiology, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou 646000, China
| | - Wei Hu
- Department of Interventional Radiology, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou 646000, China
| | - Jianfang Wang
- Department of Physics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR 999077, China
| | - Yong Liu
- Department of General Surgery (Vascular Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Xiao-Ming Zhu
- State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
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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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Chai NX, Chapiro J. Therapy of Intermediate-Stage Hepatocellular Carcinoma: Current Evidence and Clinical Practice. Semin Intervent Radiol 2020; 37:456-465. [PMID: 33328701 PMCID: PMC7732559 DOI: 10.1055/s-0040-1719186] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Intermediate-stage Hepatocellular Carcinoma (HCC) represents a wide range of disease burden. Patients with different levels of liver function, tumor size, and number of lesions may all have intermediate-stage disease according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Several minimally invasive image-guided locoregional therapies are available for the treatment of intermediate-stage HCC, including conventional transarterial chemoembolization (cTACE), drug-eluting bead TACE (DEB-TACE), yttrium-90 radioembolization (Y-90 RE), thermal ablation, bland embolization, and combination therapy. Available clinical evidence points to cTACE as the current gold standard for the locoregional treatment of intermediate-stage HCC. DEB-TACE is at best non-inferior to cTACE in terms of survival benefit. Y-90 RE is a maturing therapy, and some institutions have adopted it as first-line therapy for intermediate-stage HCC. Thermal ablation combined with TACE may be used in select patients, while bland embolization has only limited evidence for its use. The combination of locoregional therapy with VEGF inhibitors or immune checkpoint inhibitors has also been explored. This article will examine in detail the clinical evidence supporting available locoregional treatment options for intermediate-stage HCC.
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Affiliation(s)
- Nathan X. Chai
- Division of Vascular and Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut
| | - Julius Chapiro
- Division of Vascular and Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut
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Lee IJ, Lee JH, Lee YB, Kim YJ, Yoon JH, Yin YH, Lee M, Hur S, Kim HC, Jae HJ, Chung JW. Effectiveness of drug-eluting bead transarterial chemoembolization versus conventional transarterial chemoembolization for small hepatocellular carcinoma in Child-Pugh class A patients. Ther Adv Med Oncol 2019; 11:1758835919866072. [PMID: 31447948 PMCID: PMC6689910 DOI: 10.1177/1758835919866072] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Accepted: 06/30/2019] [Indexed: 01/27/2023] Open
Abstract
Background: This study aimed to compare the therapeutic effectiveness including
progression-free survival (PFS), overall survival (OS), and safety of
conventional transarterial chemoembolization (cTACE) and drug-eluting bead
transarterial chemoembolization (DEB-TACE) in a superselective fashion for
the patients with nodular hepatocellular carcinoma (HCC)
(n ⩽ 5) and Child–Pugh class A. Methods: A total of 198 consecutive patients with nodular HCCs
(n ⩽ 5) and Child–Pugh class A liver function who were
initially treated with cTACE (n = 125) or DEB-TACE
(n = 57) were included retrospectively. The primary
endpoint was PFS. Secondary endpoints included time-to-target lesion
progression (TTTLP), OS, and safety. Results: The median follow up was 62 months (range, 1–87 months). The PFS was
significantly longer in the cTACE group than in the DEB-TACE group (median,
18 months versus 7 months; hazard ratio [HR] = 0.658,
log-rank p = 0.031), whereas OS was comparable (log-rank
p = 0.299). TTTLP was significantly longer in the cTACE
group than in the DEB-TACE group (median, 34 months versus
11 months; log-rank p < 0.001). In the stratification
analysis based on tumor size, the cTACE group showed significantly longer
TTTLP than the DEB-TACE group in the 1.0–2.0 cm and 2.1–3.0 cm subgroups
(HR = 0.188, log-rank p < 0.001 and HR = 0.410,
p = 0.015, respectively) but not in the 3.1–5.0 cm and
5.1–10.0 cm subgroups (all p > 0.05). Postembolization
syndrome occurred more frequently in the cTACE group than in the DEB-TACE
group (p = 0.006). Conclusions: DEB-TACE is followed by significantly shorter PFS than cTACE in patients with
nodular HCCs (n ⩽ 5) and Child–Pugh class A, although OS is
comparable. Postembolization syndrome occurs more frequently in cTACE than
in DEB-TACE.
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Affiliation(s)
- In Joon Lee
- Department of Radiology, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yong Hu Yin
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Myungsu Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Saebeom Hur
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hwan Jun Jae
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
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Caine M, Chung T, Kilpatrick H, Bascal Z, Willis S, Tang Y, de Baere T, Dreher M, Lewis A. Evaluation of novel formulations for transarterial chemoembolization: combining elements of Lipiodol emulsions with Drug-eluting Beads. Am J Cancer Res 2019; 9:5626-5641. [PMID: 31534507 PMCID: PMC6735388 DOI: 10.7150/thno.34778] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 06/19/2019] [Indexed: 02/06/2023] Open
Abstract
There are currently two methods widely used in clinical practice to perform transarterial chemoembolization (TACE). One is based on mixing an aqueous drug with an iodized oil (Lipiodol) and creating an emulsion that is delivered intraarterially, followed by embolization with a particulate agent. The other is based on a one-step TACE using Drug-eluting Beads (DEBs) loaded with drug. It is not recommended to mix Lipiodol with DEBs due to incompatibility. For the first time, novel DEB: Lipiodol: doxorubicin (Dox) emulsions are identified using lyophilized polyvinyl alcohol (PVA) hydrogels (non-iodinated or iodinated) DEBs. Methods: 15 DEB emulsions (50mg Dox) were assessed for stability and deliverability in vitro and in vivo in a swine model. Dox release from selected formulations was measured in vitro using a vascular flow model and in vivo in a VX2 rabbit tumor model. Results: Both DEB formats were shown to be able to form emulsions, however only Iodinated DEBs consistently met defined handling criteria. Those based on the non-iodinated DEB achieved >99%+ Dox loading in <5 minutes but were generally less stable. Those prepared using iodinated DEBs, which are more hydrophobic, were able to form stable Pickering-like emulsions (separation time ≥ 20 minutes) and demonstrated handling, administration and imaging observations more akin to Lipiodol™ TACE emulsions in both embolization models. Controlled Dox release and hence beneficial in vivo pharmacokinetics associated with DEB-TACE were maintained. Conclusions: This study demonstrates that it is possible to formulate novel DEB emulsions suitable for TACE that combine positive elements of both Lipiodol™ based and DEB-TACE procedures.
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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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Lewis AL, Willis SL, Dreher MR, Tang Y, Ashrafi K, Wood BJ, Levy EB, Sharma KV, Negussie AH, Mikhail AS. Bench-to-clinic development of imageable drug-eluting embolization beads: finding the balance. Future Oncol 2018; 14:2741-2760. [PMID: 29944007 DOI: 10.2217/fon-2018-0196] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
This review describes the historical development of an imageable spherical embolic agent and focuses on work performed in collaboration between Biocompatibles UK Ltd (a BTG International group company) and the NIH to demonstrate radiopaque bead utility and bring a commercial offering to market that meets a clinical need. Various chemistries have been investigated and multiple prototypes evaluated in search of an optimized product with the right balance of handling and imaging properties. Herein, we describe the steps taken in the development of DC Bead LUMI™, the first commercially available radiopaque drug-eluting bead, ultimately leading to the first human experience of this novel embolic agent in the treatment of liver tumors.
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Affiliation(s)
- Andrew L Lewis
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, Surrey, GU15 3YL, UK
| | - Sean L Willis
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, Surrey, GU15 3YL, UK
| | - Matthew R Dreher
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, Surrey, GU15 3YL, UK
| | - Yiqing Tang
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, Surrey, GU15 3YL, UK
| | - Koorosh Ashrafi
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, Surrey, GU15 3YL, UK
| | - Bradford J Wood
- Center for Interventional Oncology, Radiology & Imaging Sciences, NIH Clinical Center, National Institute of Biomedical Imaging & Bioengineering, & National Cancer Institute Center for Cancer Research, NIH, 10 Center Drive, Bethesda, MD 20892, USA
| | - Elliot B Levy
- Center for Interventional Oncology, Radiology & Imaging Sciences, NIH Clinical Center, National Institute of Biomedical Imaging & Bioengineering, & National Cancer Institute Center for Cancer Research, NIH, 10 Center Drive, Bethesda, MD 20892, USA
| | - Karun V Sharma
- Department of Radiology & Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, Washington, DC 20010, USA
| | - Ayele H Negussie
- Center for Interventional Oncology, Radiology & Imaging Sciences, NIH Clinical Center, National Institute of Biomedical Imaging & Bioengineering, & National Cancer Institute Center for Cancer Research, NIH, 10 Center Drive, Bethesda, MD 20892, USA
| | - Andrew S Mikhail
- Center for Interventional Oncology, Radiology & Imaging Sciences, NIH Clinical Center, National Institute of Biomedical Imaging & Bioengineering, & National Cancer Institute Center for Cancer Research, NIH, 10 Center Drive, Bethesda, MD 20892, USA
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Mechanism of Action, Pharmacokinetics, Efficacy, and Safety of Transarterial Therapies Using Ethiodized Oil: Preclinical Review in Liver Cancer Models. J Vasc Interv Radiol 2017; 29:413-424. [PMID: 29289495 DOI: 10.1016/j.jvir.2017.09.025] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 09/20/2017] [Accepted: 09/27/2017] [Indexed: 02/06/2023] Open
Abstract
PURPOSE To systematically review mechanism of action, pharmacokinetics (PKs), efficacy, and safety of ethiodized oil-based locoregional therapy (LRT) for liver cancer in preclinical models. MATERIALS AND METHODS A MEDLINE search was performed from 1988 to 2016. Search terms included hepatocellular carcinoma (HCC), HCC, liver-cell carcinoma, liver, hepatic, hepatocarcinoma, transarterial or chemoembolization, TACE, animal, Lipiodol, Ethiodol, iodized oil, and/or poppy-seed oil. Inclusion criteria were: publication in a peer-reviewed journal, an accepted animal model, and PK/safety/efficacy data reported. Exclusion criteria were: inadequate PK, safety, or efficacy data; anticancer drug name/dose not available; and article not in English. Outcomes included intratumoral anticancer drug uptake, PKs, tolerance, tumor response, and survival. RESULTS Of 102 identified articles, 49 (49%) met the inclusion criteria. Seventeen, 35, and 2 articles used rat, rabbit, and pig models. Mechanism of action was investigated in 11 articles. Eleven articles reported drug uptake, PK, and tolerance data, showing 0.5%-9.5% of injected chemotherapy dose in tumor. Tumor-to-liver drug distribution ratios were 2-157. Toxicology data across 6 articles showed transient liver laboratory level elevations 1 day after LRT. There was no noteworthy liver or extrahepatic histologic damage. Nine articles reported tumor response, with 0%-30% viable tumor and -10% to -38% tumor growth at 7 days after LRT. Two articles reported survival, showing significantly longer survival after LRT vs untreated controls (56/60 d vs 33/28 d). Several articles described ethiodized oil mixed with radiopharmaceutical (n = 7), antiangiogenic (n = 6), gene (n = 6), nanoembolic (n = 5), immune (n = 2), or other novel (n = 1) agents. CONCLUSIONS Animal studies show preferential tumor uptake of anticancer agent, good hepatic/systemic tolerance, high tumor response, and enhanced survival after ethiodized oil-based LRT.
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Iodized Oil in the Portal Vein after Arterial Chemoembolization of Liver Metastases — A Caution regarding Hepatic Necrosis. Acta Radiol 2016. [DOI: 10.1177/028418519403500208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Of 20 patients with hepatic metastases from colorectal cancer treated by arterial chemoembolization, 4 showed iodized oil in peripheral branches of the portal vein. Aseptic necrosis of both the tumor and normal parenchyma in corresponding liver segments developed in 2 of these patients. They were successfully treated with antibiotics and percutaneous drainage. In the 2 remaining patients, the procedure was interrupted before complete arterial occlusion when oil was detected in the portal vein on fluoroscopy, and there was no complication. Appearance of iodized oil in the portal vein during arterial chemoembolization of colorectal liver metastases is an unfavorable event signaling the risk of liver necrosis.
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11
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Pharmacokinetics, Safety, and Efficacy of Chemoembolization with Doxorubicin-Loaded Tightly Calibrated Small Microspheres in Patients with Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 2016; 39:1379-91. [PMID: 27393274 DOI: 10.1007/s00270-016-1382-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Accepted: 05/19/2016] [Indexed: 02/08/2023]
Abstract
PURPOSE This study examines safety, efficacy, and pharmacokinetics of chemoembolization with loadable microspheres ≤100 μm for hepatocellular carcinoma. MATERIALS AND METHODS A pilot safety study was performed in 19 patients with size and dose escalation and then 52 patients were enrolled prospectively and randomly assigned to chemoembolization with TANDEM™ loaded with 150 or 100 mg of doxorubicin. RESULTS The mean diameter of the tumors was 7.28 ± 2.09 cm (range 4-12) and distribution dominant/multiple 51.9/48.1 %. Child A/B distribution was 32/20 (61.5/38.5 %) and etiology HBV/HCV/HBV/HCV-hemochromatosis was 61.6/9.6/9.6/15.4 %. Twenty-five patients were assigned in the low and 27 in the high loading group. There was 1.92 % thirty-day mortality due to lesion rupture. Biliary damage was seen in 3 patients (5.7 %) in the high loading. Mean maximum plasma concentration of doxorubicin C max ± SD was 284.9 ± 276.2 ng/mL for the high and 108.5 ± 77.6 ng/mL for the low loading (p < 0.001). According to m-RECIST overall objective response after two sessions reached 61.22 and 63.82 % at 6 months. Notably, complete target lesion response (CR) after the second session was observed in 28.57 % and maintained in 23.40 % at 6 months. No statistical differences in the local response rates were observed between the two loading groups. Overall survival (OS) at 6 months, 1 , 2, and 3 years was 98.08, 92.3, 88.46, and 82.6 %, respectively. OS and Progression-Free Survival did not demonstrate statistical significance between the two loading groups. CONCLUSION Initial evidence shows that (a) TANDEM™ achieves high rates of local response and mid-term survival, (b) high loading provides no clinical benefit and is associated with biliary toxicity.
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Jeon MJ, Gordon AC, Larson AC, Chung JW, Kim YI, Kim DH. Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer. Biomaterials 2016; 88:25-33. [PMID: 26938029 PMCID: PMC4792762 DOI: 10.1016/j.biomaterials.2016.02.021] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 02/13/2016] [Accepted: 02/17/2016] [Indexed: 12/11/2022]
Abstract
A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death.
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Affiliation(s)
- Min Jeong Jeon
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea
| | - Andrew C Gordon
- Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA
| | - Andrew C Larson
- Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA; Department of Electrical Engineering and Computer Science, Evanston, IL, USA; International Institute of Nanotechnology (IIN), Northwestern University, Evanston, IL, USA
| | - Jin Wook Chung
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea
| | - Young Il Kim
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea; Department of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates.
| | - Dong-Hyun Kim
- Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA.
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Zhuang X, Wang Q, Wang N, Hou X, Zhang J, Chi H. Effects of combining transarterial chemoembolization with percutaneous microwave coagulation therapy for hepatocellular carcinoma abutting the diaphragm. MINIM INVASIV THER 2015; 25:107-12. [PMID: 26560859 DOI: 10.3109/13645706.2015.1103751] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE This study aims to explore the clinical effectiveness of a combination therapy of transarterial chemoembolization (TACE) and percutaneous microwave coagulation therapy (PMCT) in treating hepatocellular carcinoma (HCC) abutting the diaphragm. MATERIAL AND METHODS Six cases with HCC were treated with TACE followed by PMCT one month later with the aid of artificial pneumothorax. RESULTS CT/MRI revealed complete necrosis in the tumor lesions and the treated tumor margins (≥ 5 mm). Serum alpha-fetoprotein (AFP) levels markedly declined in patients who originally had higher serum AFP levels. Postoperative complications such as fever, mild hepatic dysfunction and pleural effusion were alleviated within a short period of time. All patients were closely monitored through follow-up; all patients survived, except for one patient who received a liver transplantation. CONCLUSIONS As lesions are either invisible or poorly visible in sonography, determining an effective treatment for HCC abutting the diaphragm remains a particular challenge. TACE and PMCT combined therapy with the aid of artificial pneumothorax proved to be an available treatment option.
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Affiliation(s)
- Xingjun Zhuang
- a Department of Oncology , 401th Hospital of PLA , Qingdao , China
| | - Qinxue Wang
- b Department of Infectious , Jiaozhou People's Hospital , Jiaozhou , China
| | - Ningning Wang
- a Department of Oncology , 401th Hospital of PLA , Qingdao , China
| | - Xiaowei Hou
- a Department of Oncology , 401th Hospital of PLA , Qingdao , China
| | - Jianshun Zhang
- b Department of Infectious , Jiaozhou People's Hospital , Jiaozhou , China
| | - Hongliang Chi
- b Department of Infectious , Jiaozhou People's Hospital , Jiaozhou , China
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Qu K, Yan Z, Wu Y, Chen Y, Qu P, Xu X, Yuan P, Huang X, Xing J, Zhang H, Liu C, Zhang J. Transarterial chemoembolization aggravated peritumoral fibrosis via hypoxia-inducible factor-1α dependent pathway in hepatocellular carcinoma. J Gastroenterol Hepatol 2015; 30:925-32. [PMID: 25641377 DOI: 10.1111/jgh.12873] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/09/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM It was commonly accepted that chemotherapeutic cytotoxicity was the main cause for hepatic failure in hepatocellular carcinoma patients after repeated transarterial chemoembolization (TACE). However, the effect of embolization-induced hypoxia on liver cirrhosis has rarely been concerned. METHODS Serum levels of alanine aminotransferase, aspartate aminotransferase, and albumin were used to detect liver injury. Hepatic artery ligation was performed in carbon tetrachloride-induced rat hepatic fibrosis model to mimic the effect of hepatic hypoxia on liver fibrosis after TACE. Sirius Red staining and immunohistochemical analysis of alpha-smooth muscle actin (α-SMA) were used to detect the activation of hepatic stellate cells. Moreover, the expression of hypoxia and fibrosis-related molecules were analyzed at protein and/or mRNA level. RESULTS Patients showed a significant increase in alanine aminotransferase and aspartate aminotransferase (P = 0.006), accompanied by a decrease in albumin (P = 0.005) after repeated TACE. Hepatic artery ligation significantly promoted carbon tetrachloride-induced rat liver fibrosis progression as indicated by Sirius Red and α-SMA staining, as well as increased expression of hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-β1, and vascular endothelial growth factor (VEGF). Conditioned media of hypoxia-treated L02 cells induced the expression of Collagen I and α-SMA in LX-2 cells, which was inhibited by HIF-1α small interfering RNA. Finally, HIF-1α inhibitor LW6 attenuated the hypoxia-induced fibrosis progression in vivo. CONCLUSION Our data demonstrate that TACE-induced hepatic hypoxia aggravates the fibrosis progression in peritumoral liver tissue, thus leads to the deterioration of liver function. Intervention of HIF-1α might be a valuable strategy to optimize the efficacy and reduce the complication of TACE.
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Affiliation(s)
- Kai Qu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China
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Habib A, Desai K, Hickey R, Thornburg B, Lewandowski R, Salem R. Locoregional therapy of hepatocellular carcinoma. Clin Liver Dis 2015; 19:401-20. [PMID: 25921670 DOI: 10.1016/j.cld.2015.01.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma can be treated using minimally invasive, image-guided, catheter-based or percutaneous techniques. Such procedures offer compelling clinical outcomes with a favorable side-effect profile in a population of patients who are poor candidates for surgical or systemic treatment. This article discusses key data regarding the effectiveness of locoregional therapies in treating these patients. Disease-specific treatment is discussed in the context of hepatocellular carcinoma, with additional data discussed in the context of transplantation. As rapid innovation occurs in the realm of oncology, interventional oncology represents a safe, effective alternative that continues to generate impressive data that could potentially change treatment paradigms.
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Affiliation(s)
- Ali Habib
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Kush Desai
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Ryan Hickey
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Bartley Thornburg
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Robert Lewandowski
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Riad Salem
- Vascular and Interventional Radiology, Image-Guided Therapy, Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, 676 North St. Clair, Suite 800, Chicago, IL 60611, USA.
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Zhou B, Wang J, Yan Z. Ginsenoside Rg3 attenuates hepatoma VEGF overexpression after hepatic artery embolization in an orthotopic transplantation hepatocellular carcinoma rat model. Onco Targets Ther 2014; 7:1945-54. [PMID: 25364265 PMCID: PMC4211851 DOI: 10.2147/ott.s69830] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Background Hypoxia-induced vascular endothelial growth factor (VEGF) upregulation and angiogenesis following treatment of hepatocellular carcinoma (HCC) with transarterial embolization (TAE) or transarterial chemoembolization (TACE) may be mediated by ginsenoside Rg3, an anti-angiogenic saponin extracted from ginseng. Objective To access the synergistic action of Rg3 and TAE treatment on HCC by VEGF and it’s receptor expressions decreasing in a rat model of HCC. Methods An orthotopic transplantation HCC model was established in Buffalo rats. HCC rats were treated with hepatic artery infusions of normal saline or iodized oil (0.1 mL) with or without Rg3 (1 mg/kg) (each n=15 in control, Rg3, TAE, and TAE + Rg3 groups). At 1, 2, 4, and 8 weeks, performance status (body weight), tumor progression (longest tumor diameter), metastasis rate, microvessel density (MVD), and overall survival rate were assessed. Additionally, cluster of differentiation 31 (CD31), VEGF, VEGF receptor 2 (VEGF-R2) and VEGF-R2 phosphorylation levels were assessed by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot. Results Combined Rg3 and TAE treatment reduced tumor progression, body weight loss, angiogenesis, and metastasis rate, and led to better overall survival in the HCC rat model. ELISA results showing VEGF expression in the control, Rg3, TAE, and TAE + Rg3 groups at 4 weeks following treatment were 132.6±2.38, 37.9±0.8, 87.4±0.7, and 45.3±0.4 pg/mL, respectively. Combined Rg3 and TAE reduced the protein expression of CD31 and VEGF-R2 phosphorylation, compared with those in the TAE group at 4 weeks of treatment. Conclusion Combined Rg3 and TAE treatment limited metastasis and promoted survival by downregulating VEGF overexpression in HCC tumors. Thus, this treatment may have potential clinical implications for HCC patients undergoing TAE or TACE.
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Affiliation(s)
- Bo Zhou
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, People's Republic of China
| | - Jianhua Wang
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, People's Republic of China
| | - Zhiping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, People's Republic of China
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Murata S, Mine T, Sugihara F, Yasui D, Yamaguchi H, Ueda T, Onozawa S, Kumita SI. Interventional treatment for unresectable hepatocellular carcinoma. World J Gastroenterol 2014; 20:13453-13465. [PMID: 25309076 PMCID: PMC4188897 DOI: 10.3748/wjg.v20.i37.13453] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Revised: 04/22/2014] [Accepted: 07/25/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The Barcelona clinic liver cancer classification is the current standard classification system for the clinical management of patients with HCC and suggests that patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization (TACE). Interventional treatments such as TACE, balloon-occluded TACE, drug-eluting bead embolization, radioembolization, and combined therapies including TACE and radiofrequency ablation, continue to evolve, resulting in improved patient prognosis. However, patients with advanced-stage HCC typically receive only chemotherapy with sorafenib, a multi-kinase inhibitor, or palliative and conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. However, these patients require therapy that is more effective than sorafenib or conservative treatment. Several researchers try to perform more effective therapies, such as combined therapies (TACE with radiotherapy and sorafenib with TACE), modified TACE for HCC with arterioportal or arteriohepatic vein shunts, TACE based on hepatic hemodynamics, and isolated hepatic perfusion. This review summarizes the published data and data on important ongoing studies concerning interventional treatments for unresectable HCC and discusses the technical improvements in these interventions, particularly for advanced-stage HCC.
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Murata S, Jeppsson B, Lunderquist A, Ivancev K. Hemodynamics in rat liver tumor model during retrograde-outflow isolated hepatic perfusion with aspiration from the portal vein: angiography and in vivo microscopy. Acta Radiol 2014; 55:737-44. [PMID: 24037429 DOI: 10.1177/0284185113505258] [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] [Indexed: 12/13/2022]
Abstract
BACKGROUND Orthograde percutaneous isolated hepatic perfusion (IHP) techniques using balloon occlusion catheters are relatively simple and facilitate repeated therapy, but they result in higher rates of leakage from the perfusion circuit into the systemic circulation. Therefore, a feasible protocol for percutaneous IHP with less leakage is required. PURPOSE To investigate hemodynamic changes in rat liver and tumor during retrograde-outflow isolated hepatic perfusion (R-IHP) with aspiration from the portal vein (PV). MATERIAL AND METHODS Animal experiments were approved by the Animal Experiment Ethics Committee of Lund University. Eighteen rats underwent R-IHP after laparotomy and catheterization of the PV and hepatic artery (HA). The HA, inferior vena cava (IVC), and PV were ligated, and flow through the suprahepatic IVC was controlled with a suture loop. The rats were divided into two groups to examine blood flow during R-IHP. Four rats (group 1) underwent arteriography via the HA with and without R-IHP, and 14 rats (group 2) were inoculated with tumor and examined by in vivo fluorescence microscopy of liver and tumor during R-IHP. RESULTS In group 1, hepatic arteriography during R-IHP confirmed arterioportal communication in all four rats, with the PV acting as an outflow tract. In vivo fluorescence microscopy in group 2 showed strong enhancement of tumors, and no blood supply from the portal venules to the tumors was seen in any of the 14 rats. Blood flow in the major portion of the hepatic lobules was stopped and the percentage of enhanced area was significantly lower in the normal hepatic lobules than in the tumors (P < 0.0001). CONCLUSION We confirmed reversal of blood flow concomitant with good perfusion of the liver tumor and with reduced perfusion of normal liver parenchyma during R-IHP.
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Affiliation(s)
- Satoru Murata
- Department of Radiology, Nippon Medical School, Tokyo, Japan
| | - Bengt Jeppsson
- Department of General Surgery, Lund University and Skåne University Hospital, Malmoe, Sweden
| | - Anders Lunderquist
- Department of Radiology, Lund University and Skåne University Hospital, Malmoe, Sweden
| | - Krassi Ivancev
- Department of Radiology, University College of London Hospital, London, UK
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CT-guided irreversible electroporation in an acute porcine liver model: effect of previous transarterial iodized oil tissue marking on technical parameters, 3D computed tomographic rendering of the electroporation zone, and histopathology. Cardiovasc Intervent Radiol 2014; 38:191-200. [PMID: 24870700 DOI: 10.1007/s00270-014-0910-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2013] [Accepted: 04/03/2014] [Indexed: 12/27/2022]
Abstract
PURPOSE To evaluate the effect of previous transarterial iodized oil tissue marking (ITM) on technical parameters, three-dimensional (3D) computed tomographic (CT) rendering of the electroporation zone, and histopathology after CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a potential strategy to improve IRE performance. METHODS After Ethics Committee approval was obtained, in five landrace pigs, two IREs of the right and left liver (RL and LL) were performed under CT guidance with identical electroporation parameters. Before IRE, transarterial marking of the LL was performed with iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour after IRE, animals were killed and livers collected. Mean resulting voltage and amperage during IRE were assessed. For 3D CT rendering of the electroporation zone, parameters for size and shape were analyzed. Quantitative data were compared by the Mann-Whitney test. Histopathological differences were assessed. RESULTS Mean resulting voltage and amperage were 2,545.3 ± 66.0 V and 26.1 ± 1.8 A for RL, and 2,537.3 ± 69.0 V and 27.7 ± 1.8 A for LL without significant differences. Short axis, volume, and sphericity index were 16.5 ± 4.4 mm, 8.6 ± 3.2 cm(3), and 1.7 ± 0.3 for RL, and 18.2 ± 3.4 mm, 9.8 ± 3.8 cm(3), and 1.7 ± 0.3 for LL without significant differences. For RL and LL, the electroporation zone consisted of severely widened hepatic sinusoids containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil could be detected in the center and at the rim of the electroporation zone. CONCLUSION There is no adverse effect of previous ITM on technical parameters, 3D CT rendering of the electroporation zone, and histopathology after CT-guided IRE of the liver.
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Treatment of intermediate stage hepatocellular carcinoma: a review of intrahepatic doxorubicin drug-delivery systems. Ther Deliv 2014; 5:447-66. [DOI: 10.4155/tde.14.11] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The biopharmaceutical properties of doxorubicin delivered via two drug-delivery systems (DDSs) for the palliative treatment of unresectable hepatocellular carcinoma were reviewed with relation to the associated liver and tumor (patho)physiology. These two DDSs, doxorubicin emulsified with Lipiodol® and doxorubicin loaded into DC Bead® are different regarding tumor delivery, release rate, local bioavailability, if and how they can be given repeatedly, biodegradability, length of embolization and safety profile. There have been few direct head-to-head comparisons of these DDSs, and in-depth investigations into their in vitro and in vivo performance is warranted.
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Ogi T, Matsui O, Sanada J, Minami T, Kozaka K, Inoue D, Gabata T. Forcible intraarterial injection of a nonadhesive liquid embolic agent under microballoon occlusion: experimental study in swine liver. J Vasc Interv Radiol 2014; 25:579-585.e2. [PMID: 24508348 DOI: 10.1016/j.jvir.2013.11.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Revised: 11/28/2013] [Accepted: 11/28/2013] [Indexed: 10/25/2022] Open
Abstract
PURPOSE To evaluate the feasibility and effectiveness of transcatheter embolization by forcible intraarterial injection of a mixture of ethylene vinyl alcohol copolymer (EVAL) and ethanol under microballoon occlusion compared with conventional transcatheter arterial embolization methods in nontumoral swine liver. MATERIALS AND METHODS Nine swine were divided into three groups: embolization with EVAL/ethanol mixture (EVAL group, n = 5), with ethiodized oil (ethiodized oil group, n = 2), and with microspheres (microspheres group, n = 2). Embolization was performed at the subsegmental hepatic artery. The EVAL/ethanol mixture was injected forcibly through a microcatheter with a balloon, which was inflated to prevent backflow of the mixture during the injection. Ethiodized oil or microspheres were injected into the artery using a microcatheter without balloon occlusion. Two animals of the EVAL group were euthanized immediately after embolization, and the distribution of EVAL was assessed microscopically. The remaining seven animals were euthanized 4 weeks after embolization, and the histopathologic changes were assessed. RESULTS All procedures were technically successful. EVAL occupied > 80% of the hepatic arterial, portal venous, and sinusoidal lumens after embolization. Ischemic coagulation necrosis was observed 4 weeks after embolization in the EVAL group. Parenchymal necrosis was not observed in the ethiodized oil and microspheres groups. CONCLUSIONS Transcatheter embolization by forcible intraarterial injection of an EVAL/ethanol mixture under microballoon occlusion was feasible and achieved the simultaneous embolization of hepatic artery, portal vein, and sinusoids in swine liver, resulting in complete necrosis of the segment that received embolization.
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Affiliation(s)
- Takahiro Ogi
- Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa 920-8640, Japan.
| | - Osamu Matsui
- Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa 920-8640, Japan
| | - Junichiro Sanada
- Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa 920-8640, Japan
| | - Tetsuya Minami
- Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa 920-8640, Japan
| | - Kazuto Kozaka
- Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa 920-8640, Japan
| | - Dai Inoue
- Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa 920-8640, Japan
| | - Toshifumi Gabata
- Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa 920-8640, Japan
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Idée JM, Guiu B. Use of Lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: a review. Crit Rev Oncol Hematol 2013; 88:530-49. [PMID: 23921081 DOI: 10.1016/j.critrevonc.2013.07.003] [Citation(s) in RCA: 153] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 06/05/2013] [Accepted: 07/09/2013] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains a major public health problem. Transarterial chemoembolization (TACE) is recognized as the standard of care for patients with unresectable, asymptomatic, noninvasive and multinodular HCC. This procedure is based on percutaneous administration of a cytotoxic drug emulsified with Lipiodol followed by embolization of the tumour-feeding arteries. The standard procedure involves Lipiodol, an oily contrast medium which consists of a mixture of long-chain di-iodinated ethyl esters of poppy seed fatty acids. The aim of this review is to discuss the physical properties, tumour uptake behaviour and drug delivery effects of Lipiodol, the parameters influencing tumour uptake and future prospects. Lipiodol has a unique place in TACE as it combines three specific characteristics: drug delivery, transient and plastic embolization and radiopacity properties. Substantial heterogeneity in the physicochemical characteristics of Lipiodol/cytotoxic agent emulsions might reduce the efficacy of this procedure and justifies the current interest in Lipiodol for drug delivery.
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Affiliation(s)
- Jean-Marc Idée
- Guerbet, Research and Innovation Division, BP 57400, 95943 Roissy-Charles de Gaulle cedex, France.
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Transcatheter arterial chemoembolization based on hepatic hemodynamics for hepatocellular carcinoma. ScientificWorldJournal 2013; 2013:479805. [PMID: 23606815 PMCID: PMC3628498 DOI: 10.1155/2013/479805] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Accepted: 02/25/2013] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related deaths in the world. The Barcelona Clinic Liver Cancer (BCLC) classification has recently emerged as the standard classification system for clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, and percutaneous ablation) can improve survival in HCC patients diagnosed at an early stage and offer potential long-term curative effects. Patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization (TACE), and those diagnosed at an advanced stage receive sorafenib, a multikinase inhibitor, or conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. TACE is often recommended for advanced-stage HCC patients all over the world because these patients desire therapy that is more effective than systemic chemotherapy or conservative treatment. This paper aims to summarize both the published data and important ongoing studies for TACE and to discuss technical improvements in TACE for advanced-stage HCC.
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Rammohan A, Sathyanesan J, Ramaswami S, Lakshmanan A, Senthil-Kumar P, Srinivasan UP, Ramasamy R, Ravichandran P. Embolization of liver tumors: Past, present and future. World J Radiol 2012; 4:405-12. [PMID: 23024842 PMCID: PMC3460228 DOI: 10.4329/wjr.v4.i9.405] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Revised: 08/26/2012] [Accepted: 09/02/2012] [Indexed: 02/06/2023] Open
Abstract
Curative therapies for hepatocellular carcinoma (HCC), such as resection and liver transplantation, can only be applied in selected patients with early tumors. More advanced stages require local or systemic therapies. Resection of HCC offers the only hope for cure. Even in patients undergoing resection, recurrences are common. Chemoembolization, a technique combining intra-arterial chemotherapy with selective tumor ischemia, has been shown by randomized controlled trials to be efficacious in the palliative setting. There is now renewed interest in transarterial embolization/transarterial chemoembolization (TACE) with regards to its use as a palliative tool in a combined modality approach, as a neoadjuvant therapy, in bridging therapy before transplantation, for symptomatic indications, and even as an alternative to resection. There have also been rapid advances in the agents being embolized trans-arterially (genes, biological response modifiers, etc.). The current review provides an evidence-based overview of the past, present and future trends of TACE in patients with HCC.
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Mine T, Murata S, Ueda T, Onozawa S, Onda M, Naito Z, Kumita S. Comparative study of cisplatin-iodized oil suspension and emulsion for transcatheter arterial chemoembolization of rabbit VX2 liver tumors. Hepatol Res 2012; 42:473-81. [PMID: 22176437 DOI: 10.1111/j.1872-034x.2011.00942.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM To evaluate the antitumor effects and hepatotoxicity of transcatheter arterial chemoembolization (TACE) with cisplatin-iodized oil suspension and emulsion in a rabbit tumor model. METHODS Transcatheter arterial chemoembolization was performed on 12 rabbits with hepatic VX2 tumors using a cisplatin suspension (1 mg/kg cisplatin and 0.1 mL/kg iodized oil, n = 6) or emulsion (1 mg/kg cisplatin, 0.1 mL/kg of iodized oil, and 0.1 mL/kg saline solution, n = 6). Time series changes in plasma platinum concentration were compared over 24 h. All rabbits were killed at 7 days after TACE, and the growth ratio and residual viable proportion of tumors were calculated on the basis of ultrasonographic and histopathological findings. Hepatotoxicity was also evaluated. Differences between the two groups were statistically assessed with the Mann-Whitney U-test. The animal care committee of our institute approved this study. RESULTS Plasma platinum concentrations were significantly higher in the suspension group than in the emulsion group at 0.5-24 h after TACE (P < 0.05). Growth ratios (-24.6 ± 9.98% vs. 21.4 ± 8.87%, respectively; P = 0.004) and residual viable proportions of tumors (25.8 ± 5.02% vs. 51.1 ± 11.4%, respectively; P = 0.009) were significantly lower in the suspension group than in the emulsion group. Hepatotoxicity was transient in all rabbits. CONCLUSION Cisplatin-iodized oil suspensions facilitated the slow release of cisplatin at the tumor border. A suspension is preferable to an emulsion for drug delivery and the antitumor effect during the treatment of VX2 liver tumors with TACE.
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Affiliation(s)
- Takahiko Mine
- Departments of Radiology Integrative Pathology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
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Wang Y, Zheng C, Liang B, Zhao H, Qian J, Liang H, Feng G. Hepatocellular necrosis, apoptosis, and proliferation after transcatheter arterial embolization or chemoembolization in a standardized rabbit model. J Vasc Interv Radiol 2011; 22:1606-12. [PMID: 21959058 DOI: 10.1016/j.jvir.2011.08.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2011] [Revised: 07/23/2011] [Accepted: 08/04/2011] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To evaluate the effect of transcatheter arterial chemoembolization versus transcatheter arterial embolization on hepatocellular damage, apoptosis, proliferation, and proinflammatory response in a rabbit VX2 tumor model. MATERIALS AND METHODS Rabbits implanted with VX2 tumors in left liver lobes were randomly divided into three groups: a control group (n = 9) that underwent infusion of distilled water into the left hepatic artery, an embolization group (n = 15) that underwent left hepatic artery embolization with polyvinyl alcohol (PVA) particles, and a chemoembolization group (n = 15) that underwent left hepatic artery infusion of a mixture of 10-hydroxycamptothecin and iodized oil followed by PVA embolization. Serum and liver samples were collected at 6 hours, 3 days, and 7 days postoperatively. Liver damage was measured by liver function tests and histologic analysis. Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling were performed to quantify proliferating and apoptotic cells. Serum tumor necrosis factor (TNF)-α levels were measured to assess proinflammatory response. RESULTS Compared with embolization, chemoembolization caused liver injury with a greater increase in serum alanine aminotransferase and aspartate aminotransferase levels on days 3 and 7; histologic analysis showed increased hepatic necrosis in adjacent liver tissue beginning at day 3 and increased serum levels of TNF-α at 6 hours. By contrast, chemoembolization resulted in a slower increase in hepatocyte proliferation. Additionally, increased apoptotic hepatocytes were observed after embolization and chemoembolization. CONCLUSIONS In contrast to embolization, nonsuperselective transcatheter arterial chemoembolization increased hepatocellular damage and stimulated systemic proinflammatory cytokine release, but inhibited hepatocyte proliferation.
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Affiliation(s)
- Yong Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-fang Rd., Wuhan 430022, China
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Abstract
Comprehension of the structural and functional characteristics of the hepatic microcirculation can help improve the design, planning, and practice of imaging-guided treatment for hepatic tumors and for portal vein embolization (PVE). The hepatic microcirculation derives dual blood supply from the portal vein and the hepatic artery. The terminal portal venules directly connect to the hepatic sinusoids, but the terminal hepatic arterioles connect to arterioportal communications before entering the sinusoids: the peribiliary plexus, the terminal arteriosinus twigs, the vasa vasorum on the portal vein, and the direct arterioportal anastomosis. These communications play important roles in the balance of blood perfusion to the liver parenchyma and in controlling the blood supply to hepatic tumors and the anticipated remnant liver (in cases of PVE). At the microcirculatory level, various embolic agents present different distribution patterns. To further our understanding, iodized oil has been found to pass into the portal vein after hepatic arterial administration through the peribiliary plexus and subsequently traverses the sinusoids to enter the lungs and then the systemic circulation. Ultimately, a thorough knowledge of the host environment at the microcirculatory level is essential in developing strategies for both tumor treatment and for inducing liver regeneration.
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Affiliation(s)
- Zuxing Kan
- Division of Diagnostic Imaging, Interventional Radiology Section, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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Hepatic Arterial Embolization with Doxorubicin-Loaded Superabsorbent Polymer Microspheres in a Rabbit Liver Tumor Model. Cardiovasc Intervent Radiol 2011; 34:1021-30. [DOI: 10.1007/s00270-011-0154-6] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2010] [Accepted: 12/10/2010] [Indexed: 01/25/2023]
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Sun Z, Li G, Ai X, Luo B, Wen Y, Zhao Z, Dong S, Guan J. Hepatic and biliary damage after transarterial chemoembolization for malignant hepatic tumors: incidence, diagnosis, treatment, outcome and mechanism. Crit Rev Oncol Hematol 2010; 79:164-74. [PMID: 20719529 DOI: 10.1016/j.critrevonc.2010.07.019] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2009] [Revised: 03/19/2010] [Accepted: 07/19/2010] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To provide an overview of recent studies on transarterial chemoembolization-related hepatic and biliary damage (TRHBD) in patients with malignant hepatic tumors (MHT) and to explore the reasons for TRHBD. METHODS Literature on the treatments for MHT by TACE was sought in PubMed and the related information was summarized. RESULTS TRHBD is found to occur in the hepatic parenchymal cells, biliary tree and blood-vascular system. The damage is mainly due to ischemia resulting from embolic materials such as gelatin sponge and lipiodol. In addition, clinicians' skill levels in non-superselective catheterization, the health condition of the patients, and the chemical agents used may also be related to the damage. Most of the deterioration can be reversed if the patients are diagnosed and treated properly and promptly. CONCLUSIONS Understanding the mechanisms of TRHBD more comprehensively is helpful in developing effective methods for prevention and treatment.
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Affiliation(s)
- Zhengang Sun
- Department of Hepatobiliary Surgery, Jingzhou Central Hospital, JingZhou 4343100, Hubei Province, China
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Overall survival after transarterial lipiodol infusion chemotherapy with or without embolization for unresectable hepatocellular carcinoma: propensity score analysis. AJR Am J Roentgenol 2010; 194:830-7. [PMID: 20173167 DOI: 10.2214/ajr.09.3308] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Although iodized oil transarterial chemoembolization (TACE) has been found to have survival benefit in the care of patients with unresectable hepatocellular carcinoma, iodized oil infusion chemotherapy without embolization has not been clearly found inferior to or equal to TACE. The purpose of this study was to determine whether one of these therapies is superior to the other or the two are equal in survival benefit and whether embolization with gelatin sponge particles is indispensable to prolonging survival. SUBJECTS AND METHODS A prospective nonrandomized observational cohort study was conducted over 8 years. Among 11,030 patients with unresectable hepatocellular carcinoma, 8,507 underwent TACE, and 2,523 underwent transarterial infusion therapy with an emulsion of iodized oil and an anticancer agent as initial treatment. Patients with extrahepatic metastasis or any previous treatment were excluded. The primary end point was all-cause mortality. To minimize selection bias, propensity score analysis was used to compare the two groups. RESULTS During the follow-up period, 5,044 patients (46%) died. In the analysis of all patients, TACE was associated with a significantly higher survival rate than infusion therapy without embolization (hazard ratio, 0.60; 95% CI, 0.56-0.64; p = 0.0001). The propensity score analysis showed that the hazard ratio for death in the TACE group (n = 1,699 patients) compared with the group who underwent infusion therapy without embolization (n = 1,699) was 0.70 (95% CI, 0.63-0.76; p = 0.0001). The median survival time of the TACE group was 2.74 years, and the 1-, 3-, and 5-year survival rates were 81%, 46%, and 25%. The corresponding values for the group who underwent transarterial infusion therapy without embolization were 1.98 years and 71%, 33%, and 16%. CONCLUSION Propensity score analysis showed that in the treatment of patients with unresectable hepatocellular carcinoma, TACE was associated with significantly better overall survival rates than was transarterial infusion therapy without embolization. TACE can be recommended as initial treatment of these patients.
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Hu ML, Tai WC, Chuah SK, Chiu YC, Wu KL, Chou YP, Kuo CM, Hu TH, Chiu KW. Gastric metastasis of hepatocellular carcinoma via a possible existing retrograde hematogenous pathway. J Gastroenterol Hepatol 2010; 25:408-412. [PMID: 19929932 DOI: 10.1111/j.1440-1746.2009.06022.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND AIM Hepatocellular carcinoma (HCC) tends to metastasize to extrahepatic organs. Stomach involvement has been seldom reported and has always been considered as direct invasion. This study aims to propose a possible existing pathway for the hematogenous metastasis of HCC to the stomach. METHODS Only seven cases with stomach involvement were found from 8267 HCC patients registered at our hospital between 2000 and 2007. Their laboratory data, the findings of computed tomography and upper endoscopy, therapeutic procedures, such as esophageal variceal banding ligation (EVL), and transhepatic arterial embolization (TAE) were further studied. RESULTS All seven patients were male. Liver cirrhosis was found in six patients (6/7 = 85.7%), HCC with portal vein thrombosis (PVT) in six patients (6/7 = 85.7%), splenomegaly in five patients (5/7 = 71.4%) and esophageal varices in five patients (5/7 = 71.4%). Six patients underwent TAE and one patient underwent EVL before the development of HCC in the stomach. Four patients had HCC at the cardia, one patient at the anterior wall of the high body and two patients at the greater curvature of the high body, far away from the original HCC. Six patients eventually developed distant metastasis. HCC with gastric metastasis developed 53-126 days after TAE in five patients and 74 days after EVL in one patient. CONCLUSIONS When cirrhotic patients with portal hypertension have HCC with PVT, a hematogenous pathway can exist for gastric metastasis of tumor thrombi involving hepatofugal flow to the stomach after TAE or EVL apart from the major pathway of direct invasion.
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Affiliation(s)
- Ming-Luen Hu
- Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan
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Shin SW. The current practice of transarterial chemoembolization for the treatment of hepatocellular carcinoma. Korean J Radiol 2009; 10:425-34. [PMID: 19721826 PMCID: PMC2731859 DOI: 10.3348/kjr.2009.10.5.425] [Citation(s) in RCA: 127] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2009] [Accepted: 04/03/2009] [Indexed: 12/27/2022] Open
Abstract
Despite remarkable advancement in the surveillance and treatment of hepatocellular carcinoma (HCC) and the availability of novel curative options, a great proportion of HCC patients are still not eligible for curative treatment due to an advanced tumor stage or poor hepatic functional reserve. Therefore, there is a continuing need for effective palliative treatments. Although practiced widely, it has only recently been demonstrated that the use of transarterial chemoembolization (TACE) provides a survival benefit based on randomized controlled studies. Hence, TACE has become standard treatment in selected patients. TACE combines the effect of targeted chemotherapy with the effect of ischemic necrosis induced by arterial embolization. Most of the TACE procedures have been based on iodized oil utilizing the microembolic and drug-carrying characteristic of iodized oil. Recently, there have been efforts to improve the delivery of chemotherapeutic agents to a tumor. In this review, the basic principles, technical issues and complications of TACE are reviewed and recent advancement in TACE technique and clinical applicability are briefed.
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Affiliation(s)
- Sung Wook Shin
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Chung PJ, Park SY, Kim YI, Yoon KW, Cho SB, Choi SK, Rew JS. [Cerebral lipiodol embolism after transcatheter arterial chemoembolization of hepatocellular carcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2009; 54:130-4. [PMID: 19696542 DOI: 10.4166/kjg.2009.54.2.130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Transcatheter arterial chemoembolization (TACE) is the mainstay of treatment for unresectable hepatocellular carcinoma (HCC). Although various complications of TACE have been reported, cerebral lipiodol embolism after TACE is rare. We report a 67-year-old man, who had patent foramen ovale and developed cerebral lipiodol embolism after TACE via the inferior phrenic artery. At 20 months after third TACE of 3 cm sized HCC in the left hepatic lobe, computed tomography (CT) revealed about 1.6 cm newly developed HCC in the anterior superior segment of right hepatic lobe. The angiogram revealed the HCC was supplied from the right inferior phrenic artery. Toward the end of TACE, there were accumulations of the iodized oil in the pulmonary vasculature. Immediately after TACE, he complained of weakness in right upper and lower limbs and sensory decrease in right limbs and right hemitrunk. Magnetic resonance imaging revealed a cerebral lipiodol embolism. Transesophageal echocardiography revealed no visible thrombi but contrast-echocardiography using hand agitated saline revealed an intracardiac right to left shunt consistent with patent foramen ovale. Motor weakness and sensory decrease were gradually improved, and all neurological symptoms disappeared over 4 weeks.
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Affiliation(s)
- Pil Jin Chung
- Miraero 21 Medical Center, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
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Yang WZ, Jiang N, Huang N, Huang JY, Zheng QB, Shen Q. Combined therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation for small hepatocellular carcinoma. World J Gastroenterol 2009; 15:748-52. [PMID: 19222102 PMCID: PMC2653446 DOI: 10.3748/wjg.15.748] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the efficacy of combined transcatheter arterial chemoembolization (TACE) and percutaneous microwave coagulation therapy (PMCT) for small hepatocellular carcinoma (HCC).
METHODS: Thirty-five patients with a total of 41 HCC nodules (≤ 3 cm in diameter) were treated with TACE followed by computed tomograghy (CT)-guided percutaneous microwave coagulation therapy (PMCT) within 1-3 wk.
RESULTS: By biopsies and enhanced CT scans, complete necrosis of the tumor and 3-5 mm of the surrounding non-cancerous area were observed in 34 foci. In seven foci, incomplete necrosis of the surrounding parenchyma was observed. Serum alpha-fetoprotein (AFP) levels returned to normal 10 d after treatment in 25 patients who originally had high serum AFP levels. The follow-up period was 6-31 mo, and all patients remained alive. One patient had a recurrence in the subsegments of the liver, and another patient had a recurrence near the original lesion.
CONCLUSION: Combined therapy with TACE and PMCT is a safe and effective treatment without severe complications for small HCC.
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Hepatocellular carcinoma invading the main portal vein: treatment with transcatheter arterial chemoembolization and portal vein stenting. Cardiovasc Intervent Radiol 2008; 32:52-61. [PMID: 18931871 DOI: 10.1007/s00270-008-9454-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2008] [Revised: 08/28/2008] [Accepted: 09/19/2008] [Indexed: 12/20/2022]
Abstract
To retrospectively analyze the therapeutic results of percutaneous transhepatic portal vein stenting (PTPVS) and transcatheter arterial chemoembolization (TACE) treatment in 58 patients with hepatocellular carcinoma (HCC) invading the main portal vein (MPV). A total of 58 procedures of PTPVS were performed, immediately after which TACE was undertaken to control HCC. The clinical effects, complications, digital subtraction angiographic appearance, stent patency rates, cumulative survival rates, and predictive factors for survival were evaluated. The Kaplan-Meyer method and the log rank test were used for survival analysis. Multivariable analysis was also conducted by the Cox proportional hazard model. No patient died during stent placement or within the first 24 h. No severe procedure-related complications were observed. After stent placement, the mean +/- standard deviation portal venous pressure levels decreased from 41.43 +/- 8.56 cmH(2)O to 37.19 +/- 7.89 cmH(2)O (p < 0.01). At the time of analysis, 9 of the 58 patients survived. The 60-, 180-, 360-, and 720-day cumulative patency rates were 98.1%, 71.0%, 52.6%, and 42.1%, respectively, with a mean patency time of 552.9 +/- 88.2 days and a median patency time of 639.00 +/- 310.00 (95% confidence interval [95% CI], 31.40-1246.60) days. The 60-, 180-, 360-, and 720-day cumulative survival rates for the total study population were 74.1%, 27.1%, 17.2%, and 13.8%, respectively, with a median survival time of 113 +/- 27.29 (95% CI, 59.51-166.49) days. In the univariate analysis, the following six variables were significantly associated with the prognosis: (1) HCC type; (2) Child-Pugh grade; (3) MPV stenosis/occlusion; (4) arteriovenous shunt; (5) iodized oil deposition; and (6) number of TACE procedure. In addition, having diffuse-type HCC and Child-Pugh grade B disease were each independent factors associated with decreased survival time in the multivariate analysis. PTPVS-TACE is feasible and may be useful to control HCC invading the MPV.
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Takamatsu S, Matsui O, Gabata T, Kobayashi S, Okuda M, Ougi T, Ikehata Y, Nagano I, Nagae H. Selective induction hyperthermia following transcatheter arterial embolization with a mixture of nano-sized magnetic particles (ferucarbotran) and embolic materials: feasibility study in rabbits. ACTA ACUST UNITED AC 2008; 26:179-87. [PMID: 18509717 DOI: 10.1007/s11604-007-0212-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2007] [Accepted: 11/19/2007] [Indexed: 11/29/2022]
Abstract
PURPOSE To evaluate the possibility of selective hyperthermia following transcatheter arterial embolization (TAE) with ferucarbotran using a newly developed inductive heating (IH) device. MATERIALS AND METHODS Twelve Japanese white rabbits were separated into four groups: those treated with TAE using a mixture of ferucarbotran and lipiodol (F-L group); those treated with ferucarbotran and gelatin sponge powder; those treated with saline and lipiodol; and a control group. These four groups received IH. Nine rabbits with renal VX2 carcinoma were separated into three groups: IH after TAE (IH-TAE tumor), TAE without IH (TAE tumor), and no treatment (control tumor). The temperature of the tumor was kept at 45 degrees C for 20 min. The therapeutic effect was pathologically evaluated by TUNEL staining. RESULTS In the heating rates of the kidney, the F-L group showed significantly greater values than the group in which iron was not used. In the IH-TAE tumor group, tumors could be selectively heated. In TUNEL staining, the IH-TAE tumor and TAE tumor groups showed significantly greater values of apoptosis rate than in the control tumor group. CONCLUSION IH following TAE with a mixture of ferucarbotran and lipiodol was capable of inducing selective hyperthermia with our device. However, further investigation is needed to confirm its safety and effectiveness in the treatment of malignant neoplasms in humans.
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Affiliation(s)
- Shigeyuki Takamatsu
- Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
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Komada Y, Murata S, Tajima H, Kumita S, Kanazawa H, Tajiri T. Haemodynamic changes in the liver under balloon occlusion of a portal vein branch: evaluation with single-level dynamic computed tomography during hepatic arteriography. Clin Radiol 2007; 62:579-86. [PMID: 17467396 DOI: 10.1016/j.crad.2007.01.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2006] [Revised: 12/23/2006] [Accepted: 01/11/2007] [Indexed: 02/08/2023]
Abstract
AIM To assess haemodynamic changes in the liver under temporary occlusion of an intrahepatic portal vein. MATERIALS AND METHODS Between February 2000 and October 2004, 16 patients with hepatobiliary disease underwent single-level dynamic computed tomography during hepatic arteriography (SLD-CTHA) under temporary balloon occlusion of an intrahepatic portal vein. All patients needed percutaneous transhepatic portography for therapy of their disease. SLD-CTHA was undertaken to clarify the time-attenuation curve influenced by portal vein occlusion, and it was performed continuously over a period of 30s. The difference in absolute attenuation of the liver parenchyma in segments with occluded and non-occluded portal vein branches was determined by means of the CT number, and the difference in absolute attenuation of the occluded and non-occluded portal veins themselves was also evaluated. RESULTS SLD-CTHA demonstrated a demarcated hyperattenuation area in the corresponding distribution of the occluded portal vein branch. The attenuation of the liver parenchyma supplied by the occluded portal vein was significantly higher than that in the non-occluded area (p<0.01). The balloon-occluded portal branch enhancement in 15 of 16 cases (94%) appears due to arterio-portal communications. Failure to evaluate a remaining case for portal branch enhancement was due to absence of a visualized portal branch in the section. CONCLUSION Under temporary occlusion of an intrahepatic portal vein, hepatic angiography produced enhancement of the occluded portal branches and their corresponding parenchymal distribution; this finding is considered consistent with the presence of arterio-portal communications.
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Affiliation(s)
- Y Komada
- Department of Radiology, Center for Advanced Medical Technology, Sendagi, Tokyo, Japan.
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Madoff DC, Gupta S, Pillsbury EP, Kan Z, Tinkey PT, Stephens LC, Ensor JE, Hicks ME, Wright KC. Transarterial versus Transhepatic Portal Vein Embolization to Induce Selective Hepatic Hypertrophy: A Comparative Study in Swine. J Vasc Interv Radiol 2007; 18:79-93. [PMID: 17296708 DOI: 10.1016/j.jvir.2006.10.018] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Portal vein embolization (PVE) is used to induce liver hypertrophy for surgical candidates with marginal future liver remnant (FLR) volumes. We compared the feasibility, safety, and effectiveness of a transarterial approach for PVE (TA-PVE) with those of a transhepatic approach for PVE (TH-PVE) in a swine model. MATERIALS AND METHODS Ten experimental pigs (TA-PVE, n = 5; TH-PVE, n = 5) and six controls (TA, n = 3; TH, n = 3) were studied. For TA-PVE, a microcatheter was advanced into arteries supplying the left and left middle hepatic lobes. A 3 to 1 Ethiodol-ethanol mixture was infused into selected arteries to cross the arterioportal peribiliary plexus and remain within the portal veins (PVs). For TH-PVE, PVs in the same lobar distribution were embolized with 355- to 500-micro m polyvinyl alcohol particles and coils. Controls were similarly catheterized for saline infusion. Computed tomography with volumetry was performed before and 7, 14, 21, and 28 days after PVE to assess FLR hypertrophy (absolute FLR volume change and FLR/total liver volume [TLV]). Computed tomographic volumetry, laboratory data, and histopathology were compared between groups. RESULTS All procedures were technically successful. The increases in mean absolute FLR volume (TA-PVE, 148 +/- 84 cm(3); TH-PVE, 62 +/- 19 cm(3); P = .082), mean FLR hypertrophy (TA-PVE, 93.2%; TH-PVE, 48.4%; P = .178), and mean FLR/TLV (TA-PVE, 31.0%; TH-PVE, 16.2%; P = .130) from day 0 to day 28 between experimental groups were better for TA-PVE. Changes in laboratory data among all groups were minimal. Two complications occurred from TA-PVE (right gastric artery embolization [n = 2] without sequela) and two from TH-PVE (acute segmental right PV thrombosis [n = 1]; death 3 weeks after PVE of unknown cause [n = 1]). CONCLUSIONS Transarterial portal vein embolization is feasible, safe, and effective for inducing future liver remnant hypertrophy in swine and may represent an improvement over previously reported transhepatic portal vein embolization methods.
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Affiliation(s)
- David C Madoff
- John S Dunn Center for Radiological Sciences, Division of Diagnostic Imaging, Interventional Radiology Section, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
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Wang J, Murata S, Kumazaki T. Liver microcirculation after hepatic artery embolization with degradable starch microspheres in vivo. World J Gastroenterol 2006; 12:4214-8. [PMID: 16830378 PMCID: PMC4087377 DOI: 10.3748/wjg.v12.i26.4214] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To observe the dynamic changes of liver microcirculation in vivo after arterial embolization with degradable starch microspheres (DSM).
METHODS: DSM were injected into the proper hepatic artery through a silastic tube inserted retrogradely in gastroduodenal artery (GDA) of SD rats. Fluorescent microscopy was used to evaluate the dynamic changes of blood flow through the terminal portal venules (TPVs), sinusoids and terminal hepatic venules (THVs). The movements of DSM debris were also recorded. Six hours after injection of DSM, percentages of THVs with completely stagnant blood flow were recorded.
RESULTS: Two phases of blood flow change were recorded. In phase one: after intra-arterial injection of DSM, slow or stagnant blood flow was immediately recorded in TPVs, sinusoids and THVs. This change was reversible, and blood flow resumed completely. In phase two: after phase one, blood flow in TPVs changed again and three patterns of blood flow were recorded. Six hours after DSM injection, 36.9% ± 9.2% of THVs were found with completely stagnant blood flow.
CONCLUSION: DSM can stop the microcirculatory blood flow in some areas of liver parenchyma. Liver parenchyma supplied by arteries with larger A-P shunt is considered at a higher risk of total microcirculatory blood stagnation after injection of DSM through hepatic artery.
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Affiliation(s)
- Jian Wang
- Department of Interventional Radiology and Vascular Surgery, the First Hospital of Peking University, 100034 Beijing, China.
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Affiliation(s)
- Pierre Deltenre
- Service d'Hépato-Gastroentérologie, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
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Maataoui A, Qian J, Mack MG, Khan MF, Oppermann E, Roozru M, Schmidt S, Bechstein WO, Vogl TJ. Liver Metastases in Rats: Chemoembolization Combined with Interstitial Laser Ablation for Treatment. Radiology 2005; 237:479-84. [PMID: 16244257 DOI: 10.1148/radiol.2372041494] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
PURPOSE To assess the effect of transcatheter arterial chemoembolization (TACE) combined with laser-induced thermotherapy (LITT) for treatment of liver metastases in an animal model. MATERIALS AND METHODS All experiments were approved by the German government and the institutional animal research review board. After subcapsular liver implantation of colorectal cancer cells in 30 WAG rats (on day 0), the animals were randomly assigned to three interventional treatment groups. In the 10 rats in group A, TACE was performed: Fourteen days after cancer cell implantation and within 20 minutes after laparotomy and retrograde placement of a microcatheter into the gastroduodenal artery, these rats were injected with mitomycin (0.1 mg), iodized oil (0.1 mL), and degradable starch microspheres (5.0 mg). In the 10 rats in group B, LITT was performed: Also on day 14, the tumors in these animals were exposed to Nd:YAG laser light of 1064 nm at 2 W for 5 minutes. In the 10 rats in group C, combined treatment was administered: TACE was performed on day 14, and LITT was performed on day 21. Tumor volumes were measured before (on day 13) and after (on day 28) treatment with magnetic resonance (MR) imaging, and the mean tumor growth ratio (day 13 tumor volume divided by day 28 tumor volume) was calculated. RESULTS The mean tumor volumes measured before and after the treatments were, respectively, 0.11 and 0.60 cm(3) in group A, 0.11 and 0.68 cm(3) in group B, and 0.11 and 0.35 cm(3) in group C. The mean tumor growth ratio was 5.42 in group A, 6.14 in group B, and 3.15 in group C. According to Bonferroni test results, compared with the rats in groups A and B (controls), the group C rats had significantly inhibited tumor growth (P < .01 for both comparisons). CONCLUSION Use of combined TACE-LITT treatment, compared with the use of TACE or LITT alone, significantly inhibits tumor growth.
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Affiliation(s)
- Adel Maataoui
- Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe University, 60590 Frankfurt, Germany.
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Wu RH, Tzeng WS, Chang CM. Iodized oil embolization to brain following transcatheter arterial embolization of liver. J Gastroenterol Hepatol 2005; 20:1465-7. [PMID: 16105143 DOI: 10.1111/j.1440-1746.2005.03412.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Ikeda O, Mizukami N, Murata Y, Arakawa A, Katabuchi H, Okamoto H, Yasunaga T, Tsunawaki A, Yamashita Y. Randomized Comparison of Intra-Arterial Chemotherapy Versus Intra-Arterial Chemotherapy and Gelfoam Embolization for Treatment of Advanced Cervical Carcinoma. Cardiovasc Intervent Radiol 2005; 28:736-43. [PMID: 16132387 DOI: 10.1007/s00270-004-4178-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
PURPOSE We evaluated the effects of intra-arterial infusion therapy by comparing the results obtained with a combination of intra-arterial anticancer drugs with and without transcatheter arterial embolization (TAE) in patients with cervical cancer. METHODS Between April 1999 and March 2003, intra-arterial therapy was administered to 45 patients (mean age 49 years) with cervical cancer. Of these, 18 had stage IIb , 4 had stage IIIa, 19 had stage IIIb, and 4 had stage IVb cancer; the histopathologic types were squamous cell carcinoma (n = 35), adenocarcinoma (n = 8), and adenosquamous carcinoma (n = 2). A total of 45 patients gave their informed consent and were randomized on a continuous basis into one of three groups according to the therapeutic protocols: group A consisted of 15 patients who received cisplatin, group B consisted of 17 patients who received cisplatin, mitomycin, doxorubicin hydrochloride, and 5-fluorouracil, and group C consisted of 13 patients who received cisplatin and TAE. Each protocol was administered twice with a 3 week interval between treatments. The efficacy of treatment was evaluated on the basis of the tumor reduction ratio (%) using MR imaging and the side effects were analyzed. RESULTS In groups A, B, and C, the tumor reduction ratio was 54%, 84%, and 86%, respectively; it was significantly greater in groups B and C than in group A (p < 0.01). The difference between groups B and C was not statistically significant. Although all group C patients developed severe pain after TAE, the pain was controlled with analgesics. Thrombocytopenia occurred in 6 of 17 (35%) group B patients. CONCLUSION Group B and C patients had better tumor reduction than those in group A. Fewer hematologic complications occurred in group C patients compared with group B.
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MESH Headings
- Adult
- Aged
- Antibiotics, Antineoplastic/adverse effects
- Antibiotics, Antineoplastic/therapeutic use
- Antimetabolites, Antineoplastic/adverse effects
- Antimetabolites, Antineoplastic/therapeutic use
- Antineoplastic Agents/adverse effects
- Antineoplastic Agents/therapeutic use
- Carcinoma/diagnosis
- Carcinoma/drug therapy
- Carcinoma/therapy
- Cervix Uteri/pathology
- Cisplatin/adverse effects
- Cisplatin/therapeutic use
- Combined Modality Therapy/adverse effects
- Combined Modality Therapy/methods
- Doxorubicin/adverse effects
- Doxorubicin/therapeutic use
- Drug Therapy, Combination
- Embolization, Therapeutic/adverse effects
- Embolization, Therapeutic/methods
- Female
- Fluorouracil/adverse effects
- Fluorouracil/therapeutic use
- Gelatin Sponge, Absorbable/adverse effects
- Gelatin Sponge, Absorbable/therapeutic use
- Hemostatics/adverse effects
- Hemostatics/therapeutic use
- Humans
- Infusions, Intra-Arterial/methods
- Magnetic Resonance Imaging/methods
- Middle Aged
- Mitomycin/adverse effects
- Mitomycin/therapeutic use
- Treatment Outcome
- Uterine Cervical Neoplasms/diagnosis
- Uterine Cervical Neoplasms/drug therapy
- Uterine Cervical Neoplasms/therapy
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Affiliation(s)
- O Ikeda
- Department of Diagnostic Radiology, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, 1-1-1 Honjo, Kumamoto, 860-8505, Japan.
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Wu HP, Feng GS, Tian Y. Hepatic artery infusion of antisense oligodeoxynucleotide and lipiodol mixture transfect liver cancer in rats. World J Gastroenterol 2005; 11:2408-12. [PMID: 15832409 PMCID: PMC4305626 DOI: 10.3748/wjg.v11.i16.2408] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the distribution and stability of antisense oligodeoxynucleotide (ASODN) in Walker-256 cells and their distribution in liver, lung and kidney tissues after being infused alone or mixed with lipiodol via hepatic artery in a rat liver tumor model.
METHODS: 5’-Isothiocyananate (FITC)-labeled vascular endothelial growth factor (VEGF) ASODN was added into Walker-256 cell culture media. Its distribution in cells was observed by fluorescence microscope at different time points. Walker-256 carcinosarcoma was transplanted into Wistar rat liver to establish a liver cancer model. 5’-FITC-labeled VEGF ASODN mixed with (mixed group, n = 6) or without (TAI group, n = 6) ultra-fluid lipiodol was administrated via hepatic artery. Frozen samples of liver, lung and kidney tissue were taken from rats after 1, 3 and 6 d, respectively. The distribution of ASODN was observed under fluorescent microscope.
RESULTS: ASODN could enter cytoplasm within 2 h and nuclei within 6 h. Accumulation of ASODN reached the peak point in nuclei at 12 h, and then disappeared gradually. No fluorescence could be seen in cells at 48 h. In vivo experiment, on d 1 and 3 the fluorescence staining in liver was stronger in mixed group than in TAI group and more fluorescence could be detected in lung and kidney in TAI group than in mixed group. On d 6, no fluorescence could be detected in TAI group, but faint fluorescence could be seen in mixed group. ASODN could be seen in cancer cells and normal hepatic cells. In mixed group, ASODN was mainly distributed in liver tumor tissues.
CONCLUSION: ASODN can transfect Walker-256 cells. ASODN mixed with lipiodol infusion via hepatic artery can be used in the treatment of HCC.
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Affiliation(s)
- Han-Ping Wu
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
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Wu HP, Feng GS, Liang HM, Zheng CS, Li X. Vascular endothelial growth factor antisense oligodeoxynucleotides with lipiodol in arterial embolization of liver cancer in rats. World J Gastroenterol 2004; 10:813-8. [PMID: 15040023 PMCID: PMC4727012 DOI: 10.3748/wjg.v10.i6.813] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: Transcatheter arterial embolization (TAE) of the hepatic artery has been accepted as an effective treatment for unresectable hepatocellular carcinoma (HCC). However, embolized vessel recanalization and collateral circulation formation are the main factors of HCC growth and recurrence and metastasis after TAE. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. This study was to explore the inhibitory effect of VEGF antisense oligodeoxynucleotides (ODNs) on VEGF expression in cultured Walker-256 cells and to observe the anti-tumor effect of intra-arterial infusion of antisense ODNs mixed with lipiodol on rat liver cancer.
METHODS: VEGF antisense ODNs and sense ODNs were added to the media of non-serum cultured Walker-256 cells. Forty-eight hours later, VEGF concentrations of supernatants were detected by ELISA. Endothelial cell line ECV-304 cells were cultured in the supernatants. Seventy-two hours later, growth of ECV-304 cells was analyzed by MTT method. Thirty Walker-256 cell implanted rat liver tumor models were divided into 3 groups. 0.2 mL lipiodol (LP group, n = 10), 3OD antisense ODNs mixed with 0.2 mL lipiodol (LP+ODNs group, n = 10) and 0.2 mL normal saline (control group, n = 10) were infused into the hepatic artery. Volumes of tumors were measured by MRI before and 7 d after the treatment. VEGF mRNA in cancerous and peri-cancerous tissues was detected by RT-PCR. Microvessel density (MVD) and VEGF expression were observed by immunohistochemistry.
RESULTS: Antisense ODNs inhibited Walker-256 cells’ VEGF expression. The tumor growth rate was significantly lower in LP+ODNs group than that in LP and control groups (140.1 ± 33. 8%, 177. 9 ± 64. 9% and 403.9 ± 69.4% respectively, F = 60.019, P < 0.01). VEGF mRNAs in cancerous and peri-cancerous tissues were expressed highest in LP group and lowest in LP+ODNs group. The VEGF positive rates showed no significant difference among LP, control and LP+ODNs groups (90%, 70% and 50%, H = 3.731, P>0.05). The MVD in LP+ODNs group (53.1 ± 18.4) was significantly less than that in control group (73.2 ± 20.4) and LP group (80.3 ± 18.5) (F = 5.44, P < 0.05)
CONCLUSION: VEGF antisense ODNs can inhibit VEGF expression of Walker-256 cells. It maybe an antiangiogenesis therapy agent for malignant tumors. VEGF antisense ODNs mixed with lipiodol embolizing liver cancer is better in inhibiting liver cancer growth, VEGF expression and microvessel density than lipiodol alone.
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Affiliation(s)
- Han-Ping Wu
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
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Trinchet JC, Ganne-Carrie N, Beaugrand M. Review article: intra-arterial treatments in patients with hepatocellular carcinoma. Aliment Pharmacol Ther 2003; 17 Suppl 2:111-8. [PMID: 12786622 DOI: 10.1046/j.1365-2036.17.s2.19.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
In Western countries, most of the patients with hepatocellular carcinoma (HCC) are not eligible for curative treatments. Intra-arterial treatments have a palliative effect that could lead to extensive tumour necrosis and therefore have been widely used. Arterial embolization, Lipiodol-targeted chemoembolization and intra-arterial injection of radioactive iodine mixed with Lipiodol provided promising results in terms of tumoral growth, but were also responsible for severe side-effects, particularly in patients with cirrhosis. Their influence on survival has been assessed by randomized trials with contradictory results. In patients with advanced cases, embolization alone has limited or no influence on survival, and chemoembolization provided a beneficial effect mostly in patients with viral liver diseases, without liver failure, and with an adequate portal flux. The effects of radioactive iodine either in the treatment of advanced cases or the prevention of recurrences after a curative treatment must be investigated further.
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Affiliation(s)
- J C Trinchet
- Service d'Hépato-Gastroentérologie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris et UFR SMBH-Université Paris XIII, Bondy, France
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Shen BZ, Liu Y, Li RF, Yang G, Yu YT, Dong BW, Liang P. Effects of intraaterial chemoembolization combined with percutaneous microwave coagulation on hepatocellular carcinoma: a clinical and experimental study. Shijie Huaren Xiaohua Zazhi 2003; 11:268-271. [DOI: 10.11569/wcjd.v11.i3.268] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the role of microwave coagulation for liver cancer after occlusion of hepatic artery in animal experiment and clinical study.
METHODS: Total 24 suitable hepatic lobes of ten dogs were separated into two groups. Microwave coagulation alone (control group) or after hepatic artery occlusion (experiment group) was performed respectively. The power of irradiation was 50 W and the duration was 300 and 400 seconds. Clinically, 25 patients with hepatocellular carcinoma (30 nodules) were treated with PMCT after TACE. The TACE was performed 1-3 times and PMCT 1-2 times totally in every patients.
RESULTS: In animal experiment, the coagulated area was elliptic in control group and was elliptic or round in experimental group. The volume of coagulated tissue in experimental group was 3.8 times bigger than that in control. Clinically, all the lesions in contrast-enhanced CT showed slight enhancement or no enhancement after treatment. Intratumoral blood flow decreased significantly in 6 patients and disappeared in 20 patients. In 19 patients with elevated a-fetoprotein, the level decreased in all patients and was normalized in 14. There were no significant side- effects.
CONCLUSION: PMCT after TACE can significantly enlarge the necrosis volume of microwave coagulation, and promote the efficacy of treatment for hepatocellular carcinoma.
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Ahrar K, Gupta S. Hepatic artery embolization for hepatocellular carcinoma: technique, patient selection, and outcomes. Surg Oncol Clin N Am 2003; 12:105-26. [PMID: 12735133 DOI: 10.1016/s1055-3207(02)00089-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Most patients with HCC do not qualify for surgical interventions. In carefully selected patients, TACE may improve survival, reduce the rate of tumor growth, and decrease the incidence of portal vein occlusion. Since the introduction of TACE in the 1980s, the technical aspects of the procedure have significantly improved. Sophisticated angiographic equipment and techniques have made superselective arterial catheterization possible for more focused drug delivery. The use of ethiodized oil allows for more effective targeting of HCC and provides dual embolization of the hepatic artery and the portal venules supplying the tumor. Many important technical questions about TACE remain unanswered at this time: there are no reliable, standardized patient selection criteria, ideal cytotoxic agents have not yet been identified, the optimal dose of ethiodized oil has not been confirmed, and the optimal frequency and timing of repeat treatment sessions remain unknown. One major limitation of TACE--the need for repeated treatments, which can result in deterioration of liver function--may be avoided by use of a combination of interventional therapies. The combination of limited TACE with PEI or RFA may lead to improved survival and decreased risk of liver failure. More recently, two excellent randomized clinical trials have demonstrated significant survival benefit for patients treated with TACE when compared with those treated symptomatically.
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Affiliation(s)
- Kamran Ahrar
- Section of Vascular and Interventional Radiology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 325, Houston, TX 77030, USA.
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Li X, Zheng CS, Feng GS, Zhuo CK, Zhao JG, Liu X. An implantable rat liver tumor model for experimental transarterial chemoembolization therapy and its imaging features. World J Gastroenterol 2002; 8:1035-9. [PMID: 12439920 PMCID: PMC4656375 DOI: 10.3748/wjg.v8.i6.1035] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To establish an ideal implantable rat liver tumor model for interventional therapy study and examine its angiographic signs and MRI, CT features before and after embolization.
METHODS: Forty male Wistar rats were implanted with Walker-256 tumor in the left lateral lobe of liver. Digital subtraction angiography (DSA) and transarterial chemoembolization were performed on day 14 after implantation. Native computer tomography (CT, n = 8) and native magnetic resonance (MR, n = 40) were performed between the day 8 and day 21 after implantation. The radiological morphological characteristics were correlated with histological findings.
RESULTS: Successful implantation was achieved in all forty rats, which was confirmed by CT and MRI. MR allowed tumor visualization from day 8 while CT from day 11 after implantation. The tumors were hypodensity on CT, hypointense on MR T1-weighted and hyperintense on T2-weighted. The model closely resembled human hepatocarcinoma in growth pattern and the lesions were rich in vasculature on angiography and got its filling mainly from the hepatic artery. Before therapy, tumor size was 211.9 ± 48.7 mm3. No ascites, satellite liver nodules or lung metastasis were found. One week after therapy, tumor size was 963.6 ± 214.8 mm3 in the control group and 356.5 ± 78.4 mm3 in TACE group. Ascites (4/40), satellite liver nodules (7/40) or lung metastasis (3/40) could be seen on day 21.
CONCLUSION: Walker-256 tumor rat model is suitable for the interventional experiment. CT and MRI are helpful in animal optioning and evaluating experimental results.
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Affiliation(s)
- Xin Li
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province, China.
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