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Wagner MG, Whitehead JF, Periyasamy S, Laeseke PF, Speidel MA. Spatiotemporal frequency domain analysis for blood velocity measurement during embolization procedures. Med Phys 2024; 51:1726-1737. [PMID: 37665770 PMCID: PMC10909916 DOI: 10.1002/mp.16715] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 09/06/2023] Open
Abstract
BACKGROUND Currently, determining procedural endpoints and treatment efficacy of vascular interventions is largely qualitative and relies on subjective visual assessment of digital subtraction angiography (DSA) images leading to large interobserver variabilities and poor reproducibility. Quantitative metrics such as the residual blood velocity in embolized vessel branches could help establish objective and reproducible endpoints. Recently, velocity quantification techniques based on a contrast enhanced X-ray sequence such as qDSA and 4D DSA have been proposed. These techniques must be robust, and, to avoid radiation dose concerns, they should be compatible with low dose per frame image acquisition. PURPOSE To develop and evaluate a technique for robust blood velocity quantification from low dose contrast enhanced X-ray image sequences that leverages the oscillating signal created by pulsatile blood flow. METHODS The proposed spatiotemporal frequency domain (STF) approach quantifies velocities from time attenuation maps (TAMs) representing the oscillating signal over time for all points along a vessel centerline. Due to the time it takes a contrast bolus to travel along the vessel centerline, the resulting TAM resembles a sheared sine wave. The shear angle is related to the velocity and can be determined in the spatiotemporal frequency domain after applying the 2D Fourier transform to the TAM. The approach was evaluated in a straight tube phantom using three different radiation dose levels and compared to ultrasound transit-time-based measurements. The STF velocity results were also compared to previously published approaches for the measurement of blood velocity from contrast enhanced X-ray sequences including shifted least squared (SLS) and phase shift (PHS). Additionally, an in vivo porcine study (n = 8) was performed where increasing amounts of embolic particles were injected into a hepatic or splenic artery with intermittent velocity measurements after each injection to monitor the resulting reduction in velocity. RESULTS At the lowest evaluated dose level (average air kerma rate 1.3 mGy/s at the interventional reference point), the Pearson correlation between ultrasound and STF velocity measurements was99 % $99\%$ . This was significantly higher (p < 0.0001 $p < 0.0001$ ) than corresponding correlation results between ultrasound and the previously published SLS and PHS approaches (91 $\hskip.001pt 91$ and93 % $93\%$ , respectively). In the in vivo study, a reduction in velocity was observed in85.7 % $85.7\%$ of cases after injection of 1 mL,96.4 % $96.4\%$ after 3 mL, and100.0 % $100.0\%$ after 4 mL of embolic particles. CONCLUSIONS The results show good agreement of the spatiotemporal frequency domain approach with ultrasound even in low dose per frame image sequences. Additionally, the in vivo study demonstrates the ability to monitor the physiological changes due to embolization. This could provide quantitative metrics during vascular procedures to establish objective and reproducible endpoints.
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Affiliation(s)
- Martin G Wagner
- Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
- Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, USA
| | - Joseph F Whitehead
- Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, USA
| | - Sarvesh Periyasamy
- Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
| | - Paul F Laeseke
- Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
| | - Michael A Speidel
- Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, USA
- Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA
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Balli HT, Aikimbaev K. Intra-arterial Chemotherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma. LIVER CANCER IN THE MIDDLE EAST 2021:171-187. [DOI: 10.1007/978-3-030-78737-0_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Li X, He J, Ren X, Zhao H, Zhao H. Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway. Diagn Pathol 2020; 15:141. [PMID: 33308276 PMCID: PMC7733254 DOI: 10.1186/s13000-020-01056-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 11/29/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The involvement of circular RNAs (circRNAs) in chemoresistance of tumors has been identified. Herein, this study aims to investigate the role and the underlying mechanism of circ_0003998 in doxorubicin (DOX) resistance in hepatocellular carcinoma (HCC). METHODS The expression of circ_0003998 and microRNA (miR)-218-5p and eukaryotic translation initiation factor 5A-2 (EIF5A2) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability, migration and invasion were analyzed using cell counting kit-8, colony formation and transwell assay, respectively. The levels of matrix metallopeptidase 9 (MMP-9), E-cadherin, Vimentin, N-cadherin and EIF5A2 protein were detected using western blot. The interaction between miR-218-5p and circ_0003998 or EIF5A2 was confirmed by dual-luciferase reporter assay. In vivo experiments were performed using murine xenograft models. RESULTS Circ_0003998 was elevated in HCC tissues, DOX-resistant tissues and cells, and circ_0003998 knockdown promoted DOX-sensitivity in HCC by inhibiting resistant cell viability, migration, invasion and EMT in vitro and enhanced DOX cytotoxicity in vivo. Bioinformatics analysis revealed circ_0003998 inhibited miR-218-5p expression, which was clarified to be a target of circ_0003998, and circ_0003998 knockdown sensitized HCC cell to DOX by sponging miR-218-5p. EIF5A2 was a target of miR-218-5p, and miR-218-5p mitigated DOX resistance in HCC cells through modulating EIF5A2 expression. Additionally, circ_0003998 served as a competing endogenous RNA for miR-218-5p to regulate EIF5A2 expression. CONCLUSION Circ_0003998 knockdown sensitized HCC cell to DOX by regulating miR-218-5p/EIF5A2 axis, indicating new markers of poor response to DOX and potential therapeutic strategies for the chemotherapy of HCC.
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Affiliation(s)
- Xiaomin Li
- Shanxi Medical University, Taiyuan, Shanxi, China
- Department of General Surgery, Shanxi Bethune Hospital, No. 99 Longcheng Street, Xiaodian District, Taiyuan, 030032, Shanxi, China
| | - Jiefeng He
- Department of General Surgery, Shanxi Bethune Hospital, No. 99 Longcheng Street, Xiaodian District, Taiyuan, 030032, Shanxi, China
| | - Xiaojing Ren
- Department of General Surgery, Shanxi Bethune Hospital, No. 99 Longcheng Street, Xiaodian District, Taiyuan, 030032, Shanxi, China
| | - Haichao Zhao
- Department of General Surgery, Shanxi Bethune Hospital, No. 99 Longcheng Street, Xiaodian District, Taiyuan, 030032, Shanxi, China
| | - Haoliang Zhao
- Department of General Surgery, Shanxi Bethune Hospital, No. 99 Longcheng Street, Xiaodian District, Taiyuan, 030032, Shanxi, China.
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Pang F, Li Y, Zhang W, Xia C, He Q, Li Z, Xiao L, Song S, Dong P, Zhou H, Shao T, Cai H, Li L. Biodegradable 131 Iodine-Labeled Microspheres: Potential Transarterial Radioembolization Biomaterial for Primary Hepatocellular Carcinoma Treatment. Adv Healthc Mater 2020; 9:e2000028. [PMID: 32431090 DOI: 10.1002/adhm.202000028] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 04/28/2020] [Indexed: 02/05/2023]
Abstract
Transarterial radioembolization with radionuclide-labeled microspheres is successfully used in hepatocellular carcinoma (HCC) treatment, but the non-biodegradability and rapid settlement of the microsphere material are associated with unsatisfied distribution and unable for multiple administrations. In this study, a novel biodegradable chitosan-collagen composite microsphere (CCM) with ideal settlement rate is prepared. The Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) results indicate CCMs have desirable shapes with diameters around 10 µm, and considerable biodegradability within 12 weeks. These CCMs are successfully radiolabeled with 131 I and processed efficiency of 70.4 MBq mg-1 of microspheres as well as favorable stability in vitro. Then, 131 I-CCMs are injected into rats with orthotopic HCC via the hepatic artery which effectively improves the median overall survival from 19 to 44 days (p < 0.05). Single photon emission computed tomography (SPECT/CT) imaging and immunohistochemical analysis indicate well-localized biodistribution and consistent stability of 131 I-CCMs in the liver over 28 days. Magnetic resonance imaging (MRI) and gross specimens monitoring confirm the inhibited tumor growth after 131 I-CCMs treatment. In conclusion, these biodegradable 131 I-CCMs exhibit optimal radiolabeling efficiency, stability, and favorably radioembolization effect for orthotopic HCC in a rodent model, suggesting potential for interventional cancer therapy.
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Affiliation(s)
- Fuwen Pang
- Laboratory of Clinical Nuclear MedicineDepartment of Nuclear MedicineWest China Hospital of Sichuan University Chengdu 610041 China
| | - Yuhao Li
- Laboratory of Clinical Nuclear MedicineDepartment of Nuclear MedicineWest China Hospital of Sichuan University Chengdu 610041 China
| | - Wenjie Zhang
- Laboratory of Clinical Nuclear MedicineDepartment of Nuclear MedicineWest China Hospital of Sichuan University Chengdu 610041 China
| | - Chunchao Xia
- Department of RadiologyWest China Hospital of Sichuan University Chengdu 610041 China
| | - Qing He
- Department of OncologyWest China Hospital of Sichuan University Chengdu 610041 China
| | - Zhenlin Li
- Department of RadiologyWest China Hospital of Sichuan University Chengdu 610041 China
| | - Liu Xiao
- Laboratory of Clinical Nuclear MedicineDepartment of Nuclear MedicineWest China Hospital of Sichuan University Chengdu 610041 China
| | - Simin Song
- Department of Nuclear MedicineCentral Hospital Guangyuan China
| | - Ping Dong
- Laboratory of Clinical Nuclear MedicineDepartment of Nuclear MedicineWest China Hospital of Sichuan University Chengdu 610041 China
| | - Huijun Zhou
- Laboratory of Clinical Nuclear MedicineDepartment of Nuclear MedicineWest China Hospital of Sichuan University Chengdu 610041 China
| | - Tuo Shao
- Division of Nuclear Medicine and Molecular ImagingMassachusetts General Hospital & Department of RadiologyHarvard Medical School Boston MA 02114 USA
| | - Huawei Cai
- Laboratory of Clinical Nuclear MedicineDepartment of Nuclear MedicineWest China Hospital of Sichuan University Chengdu 610041 China
| | - Lin Li
- Laboratory of Clinical Nuclear MedicineDepartment of Nuclear MedicineWest China Hospital of Sichuan University Chengdu 610041 China
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Watanabe Y, Ogawa M, Kumagawa M, Hirayama M, Miura T, Matsumoto N, Nakagawara H, Yamamoto T, Moriyama M. Utility of Contrast-Enhanced Ultrasound for Early Therapeutic Evaluation of Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2020; 39:431-440. [PMID: 31436341 DOI: 10.1002/jum.15118] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 08/03/2019] [Indexed: 06/10/2023]
Abstract
OBJECTIVES We aimed to investigate whether contrast-enhanced ultrasound (CEUS) could be useful for early evaluation of the treatment response to transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). METHODS This study retrospectively selected HCCs in which homogeneous retention of iodized oil was confirmed on non-contrast-enhanced computed tomography performed immediately after TACE. Therapeutic responses of HCCs were evaluated by CEUS 1 to 2 days after TACE and by contrast-enhanced computed tomography (CECT) approximately 4 weeks after TACE. We investigated the noninferiority of CEUS 1 to 2 days after TACE to CECT approximately 4 weeks after TACE in terms of the diagnostic accuracy of the therapeutic response to TACE on HCC. RESULTS Eighty-nine HCCs were enrolled in this study between April 2014 and June 2016. A complete response was observed in 57 of 89 nodules (64.0%), and an incomplete response was observed in the remaining 32 nodules (36.0%). The accuracy rates for CEUS 1 to 2 days after TACE and CECT approximately 4 weeks after TACE in the therapeutic effect of TACE on HCCs were 83.1% (95% confidence interval, 73.7%-90.2%) and 83.1% (95% confidence interval, 73.7%-90.2%), respectively. The difference in diagnostic accuracy between methods was 0%, which was below the predetermined noninferiority limit of 15%, and CEUS 1 to 2 days after TACE was noninferior to CECT approximately 4 weeks after TACE. CONCLUSIONS Our results suggest that CEUS is a useful modality for early therapeutic evaluation of TACE for HCC, and we can thus plan the next treatment strategies for HCC within a few days after TACE.
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Affiliation(s)
- Yukinobu Watanabe
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Masahiro Ogawa
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Mariko Kumagawa
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Midori Hirayama
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Takao Miura
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Naoki Matsumoto
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Hiroshi Nakagawara
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Toshiki Yamamoto
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Mitsuhiko Moriyama
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
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Lee GC, Gamblin TC, Qadan M. Percutaneous Transcatheter Particle Therapies. CANCER REGIONAL THERAPY 2020:265-279. [DOI: 10.1007/978-3-030-28891-4_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Tu C, Chen W, Wang S, Tan W, Guo J, Shao C, Wang W. MicroRNA-383 inhibits doxorubicin resistance in hepatocellular carcinoma by targeting eukaryotic translation initiation factor 5A2. J Cell Mol Med 2019; 23:7190-7199. [PMID: 30801960 PMCID: PMC6815770 DOI: 10.1111/jcmm.14197] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 01/02/2019] [Accepted: 01/10/2019] [Indexed: 12/19/2022] Open
Abstract
Drug resistance occurs commonly in cancers, especially in hepatocellular carcinoma (HCC). Accumulating evidence has demonstrated that microRNAs (miRNAs) play a vital role in tumour chemoresistance. However, little is known about the role of miR-383 in HCC chemoresistance. In the present study, RT-PCR and western blotting were used to identify the expression profile of miR-383 and eukaryotic translation initiation factor 5A2 (EIF5A2). The bioinformatics website Targetscan was used to predict the target genes of miR-383. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and potential mechanism of the miR-383/EIF5A2 axis in chemoresistance of HCC cells. The expression level of miR-383 correlated negatively with doxorubicin (Dox) sensitivity. Overexpression of miR-383 promoted HCC cells to undergo Dox-induced cytotoxicity and apoptosis, whereas miR-383 knockdown had the opposite effects. EIF5A2 was predicted as a target gene of miR-383. EIF5A2 knockdown sensitized HCC cells to Dox. Moreover, miR-383 inhibition-mediated HCC Dox resistance could be reversed by silencing EIF5A2. Finally, we demonstrated that miR-383 inhibition could enhance Dox sensitivity by targeting EIF5A2 in vivo. The results indicated that miR-383 inhibited Dox resistance in HCC cells by targeting EIF5A2. Targeting the miR-383/EIF5A2 axis might help to alleviate the chemoresistance of HCC cells.
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MESH Headings
- Animals
- Antibiotics, Antineoplastic/pharmacology
- Apoptosis
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/metabolism
- Carcinoma, Hepatocellular/pathology
- Cell Proliferation
- Doxorubicin/pharmacology
- Drug Resistance, Neoplasm/genetics
- Gene Expression Regulation, Neoplastic/drug effects
- Humans
- Liver Neoplasms/drug therapy
- Liver Neoplasms/genetics
- Liver Neoplasms/metabolism
- Liver Neoplasms/pathology
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- MicroRNAs/genetics
- Peptide Initiation Factors/genetics
- Peptide Initiation Factors/metabolism
- Prognosis
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
- Eukaryotic Translation Initiation Factor 5A
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Affiliation(s)
- Chaoyong Tu
- Department of Hepatobiliary and Pancreatic SurgeryThe Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangP.R. China
- Department of Hepatobiliary and Pancreatic Surgery, Lishui HospitalZhejiang University School of Medicine, The Fifth Affiliated Hospital of Wenzhou Medical UniversityLishuiZhejiangP.R. China
| | - Wei Chen
- Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated traditional Chinese and Western MedicineZhejiang Academy of Traditional Chinese MedicineHangzhouZhejiangChina
| | - Shuqian Wang
- Division of Breast Surgery, Department of SurgeryThe First Affiliated Hospital, School of Medicine, Zhejiang UniversityHangzhouZhejiangP.R. China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang ProvinceThe First Affiliated Hospital, School of Medicine, Zhejiang UniversityHangzhouZhejiangP.R. China
| | - Wei Tan
- Department of Hepatobiliary and Pancreatic Surgery, Lishui HospitalZhejiang University School of Medicine, The Fifth Affiliated Hospital of Wenzhou Medical UniversityLishuiZhejiangP.R. China
| | - Jingqiang Guo
- Department of Hepatobiliary and Pancreatic Surgery, Lishui HospitalZhejiang University School of Medicine, The Fifth Affiliated Hospital of Wenzhou Medical UniversityLishuiZhejiangP.R. China
| | - Chuxiao Shao
- Department of Hepatobiliary and Pancreatic Surgery, Lishui HospitalZhejiang University School of Medicine, The Fifth Affiliated Hospital of Wenzhou Medical UniversityLishuiZhejiangP.R. China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic SurgeryThe Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangP.R. China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang ProvinceThe First Affiliated Hospital, School of Medicine, Zhejiang UniversityHangzhouZhejiangP.R. China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, School of MedicineThe First Affiliated Hospital, Zhejiang UniversityHangzhouZhejiangP.R. China
- State Key Laboratory & Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseaseZhejiang UniversityHangzhouZhejiangP.R. China
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Pratama MY, Pascut D, Massi MN, Tiribelli C. The role of microRNA in the resistance to treatment of hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:577. [PMID: 31807558 DOI: 10.21037/atm.2019.09.142] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death with a limited efficacy of treatment for intermediate and advanced stages of the disease. Several therapeutic approaches such as trans-arterial chemoembolization (TACE) with anthracyclines, cisplatin and multikinase inhibitor sorafenib have been appealing choices of treatments yet failed to reach a satisfactory outcome mainly due to the numerous mechanisms that influence patient's response. MicroRNAs (miRNAs) are key regulators of many intracellular processes related to drug resistance. This phenomenon has been linked to the modulation of several complex pathways, ranging from the loss of ability of drug accumulation, protective mechanism of autophagy, adaptive mechanism of cancer cells towards the drugs-induced environment, decrease DNA damage and suppression of downstream events that transduce its signal into apoptosis. We summarize the recent findings on the involvement of miRNAs in various drug resistance-related mechanisms in the development of resistance to anthracyclines, cisplatin and sorafenib therapies. Furthermore, we describe the possible application of miRNAs as circulating biomarkers predicting therapy response in HCC. Thus, the undeniable potential and paramount role of miRNA in drug resistance may eventually lead to improved clinical strategies and outcomes for HCC patients.
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Affiliation(s)
- Muhammad Yogi Pratama
- Fondazione Italiana Fegato, AREA Science Park Bazovizza, Trieste, Italy.,Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia
| | - Devis Pascut
- Fondazione Italiana Fegato, AREA Science Park Bazovizza, Trieste, Italy
| | | | - Claudio Tiribelli
- Fondazione Italiana Fegato, AREA Science Park Bazovizza, Trieste, Italy
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Wei Y, Liu J, Yan M, Zhao S, Long Y, Zhang W. Effectiveness and Safety of Combination Therapy of Transarterial Chemoembolization and Apatinib for Unresectable Hepatocellular Carcinoma in the Chinese Population: A Meta-Analysis. Chemotherapy 2019; 64:94-104. [PMID: 31569090 DOI: 10.1159/000502510] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 08/05/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND The combination of transarterial chemoembolization (TACE) and apatinib has been used in the treatment of intermediate or advanced hepatocellular carcinoma (HCC). However, its effectiveness and safety are also argued. METHODS Eligible studies were collected from a computer search of literatures published from the database establishment to May 2019 in PubMed, Web of Science, EMBASE, Ovid, the Cochrane Library, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine Disc. The objective response rate (ORR), the disease control rate (DCR), survival rate (SR), and the incidences of treatment-related adverse effects (AEs) were collected as the relevant outcomes. Data were analyzed through fixed/random effects of meta-analysis models with RevMan 5.3 software. RESULTS Eight randomized controlled clinical trials comprising 528 patients and 4 cohort studies comprising 226 patients were eventually included. Compared to the control group treated with TACE solely, combination therapy group, in which intermediate or advanced HCC patients were treated with TACE and apatinib, significantly enhanced ORR (relative risk [RR] 2.06, 95% CI 1.63-2.61, p < 0.001), DCR (RR 1.65, 95% CI 1.24-2.20, p < 0.001), and whole SRs of 6-month (RR 1.52, 95% CI 1.08-2.14, p = 0.02), 1-year (RR 1.52, 95% CI 1.25-1.84, p < 0.001), and 2-year (RR 1.84, 95% CI 1.34-2.54, p < 0.001). The incidence of hand foot syndrome, proteinuria, hypertension, and diarrhea was significantly increased in the combination therapy group compared with the control group (p < 0.05), and the incidence of nausea and vomiting, fever, and myelosuppression, respectively, was similar in 2 groups (p > 0.05). CONCLUSIONS The combination therapy of TACE and apatinib can enhance the clinical effectiveness better than TACE solely in patients with intermediate or advanced HCC, while increase in the AEs is usually tolerable.
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Affiliation(s)
- Yan Wei
- Department of Gastroenterology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, China.,Department of Outpatient, 986th Military Hospital, Xi'an, China
| | - Jianjun Liu
- Department of Outpatient, 986th Military Hospital, Xi'an, China
| | - Min Yan
- Department of Epidemiology, School of Public Health, The Fourth Military Medical University, Xi'an, China
| | - Shuguang Zhao
- Department of Gastroenterology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, China
| | - Yong Long
- Department of Epidemiology, School of Public Health, The Fourth Military Medical University, Xi'an, China
| | - Weilu Zhang
- Department of Epidemiology, School of Public Health, The Fourth Military Medical University, Xi'an, China,
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Katsanos K, Kitrou P, Spiliopoulos S, Maroulis I, Petsas T, Karnabatidis D. Comparative effectiveness of different transarterial embolization therapies alone or in combination with local ablative or adjuvant systemic treatments for unresectable hepatocellular carcinoma: A network meta-analysis of randomized controlled trials. PLoS One 2017; 12:e0184597. [PMID: 28934265 PMCID: PMC5608206 DOI: 10.1371/journal.pone.0184597] [Citation(s) in RCA: 94] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Accepted: 08/26/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The optimal transcatheter embolization strategy for patients with unresectable hepatocellular carcinoma (HCC) remains elusive. We conducted a systematic review and network meta-analysis (NMA) of different embolization options for unresectable HCC. METHODS Medical databases were searched for randomized controlled trials evaluating bland transarterial embolization (TAE), conventional TACE, drug-eluting bead chemoembolization (DEB-TACE), or transarterial radioembolization (TARE), either alone or combined with adjuvant chemotherapy, or local liver ablation, or external radiotherapy for unresectable HCC up to June 2017. Random effects Bayesian models with a binomial and normal likelihood were fitted (WinBUGS). Primary endpoint was patient survival expressed as hazard ratios (HR) and 95% credible intervals. An exponential model was used to fit patient survival curves. Safety and objective response were calculated as odds ratios (OR) and accompanying 95% credible intervals. Competing treatments were ranked with the SUCRA statistic. Heterogeneity-adjusted effective sample sizes were calculated to evaluate information size for each comparison. Quality of evidence (QoE) was assessed with the GRADE system adapted for NMA reports. All analyses complied with the ISPOR-AMCP-NCP Task Force Report for good practice in NMA. FINDINGS The network of evidence included 55 RCTs (12 direct comparisons) with 5,763 patients with preserved liver function and unresectable HCC (intermediate to advanced stage). All embolization strategies achieved a significant survival gain over control treatment (HR range, 0.42-0.76; very low-to-moderate QoE). However, TACE, DEB-TACE, TARE and adjuvant systemic agents did not confer any survival benefit over bland TAE alone (moderate QoE, except low in case of TARE). There was moderate QoE that TACE combined with external radiation or liver ablation achieved the best patient survival (SUCRA 86% and 96%, respectively). Estimated median survival was 13.9 months in control, 18.1 months in TACE, 20.6 months with DEB-TACE, 20.8 months with bland TAE, 30.1 months in TACE plus external radiotherapy, and 33.3 months in TACE plus liver ablation. TARE was the safest treatment (SUCRA 77%), however, all examined therapies were associated with a significantly higher risk of toxicity over control (OR range, 6.35 to 68.5). TACE, DEB-TACE, TARE and adjuvant systemic agents did not improve objective response over bland embolization alone (OR range, 0.85 to 1.65). There was clinical diversity among included randomized controlled trials, but statistical heterogeneity was low. CONCLUSIONS Chemo- and radio-embolization for unresectable hepatocellular carcinoma may improve tumour objective response and patient survival, but are not more effective than bland particle embolization. Chemoembolization combined with external radiotherapy or local liver ablation may significantly improve tumour response and patient survival rates over embolization monotherapies. Quality of evidence remains mostly low to moderate because of clinical diversity. SYSTEMATIC REVIEW REGISTRATION CRD42016035796 (http://www.crd.york.ac.uk/PROSPERO).
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Affiliation(s)
- Konstantinos Katsanos
- Department of Interventional Radiology, Patras University Hospital, School of Medicine, Rion, Greece
- Department of Interventional Radiology, Guy's and St. Thomas' Hospitals, NHS Foundation Trust, King's Health Partners, London, United Kingdom
| | - Panagiotis Kitrou
- Department of Interventional Radiology, Patras University Hospital, School of Medicine, Rion, Greece
| | - Stavros Spiliopoulos
- Department of Interventional Radiology, Attikon University Hospital, School of Medicine, Athens, Greece
| | - Ioannis Maroulis
- Department of Liver Surgery, Patras University Hospital, School of Medicine, Rion, Greece
| | - Theodore Petsas
- Department of Interventional Radiology, Patras University Hospital, School of Medicine, Rion, Greece
| | - Dimitris Karnabatidis
- Department of Interventional Radiology, Patras University Hospital, School of Medicine, Rion, Greece
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Bossé D, Ng T, Ahmad C, Alfakeeh A, Alruzug I, Biagi J, Brierley J, Chaudhury P, Cleary S, Colwell B, Cripps C, Dawson LA, Dorreen M, Ferland E, Galiatsatos P, Girard S, Gray S, Halwani F, Kopek N, Mahmud A, Martel G, Robillard L, Samson B, Seal M, Siddiqui J, Sideris L, Snow S, Thirwell M, Vickers M, Goodwin R, Goel R, Hsu T, Tsvetkova E, Ward B, Asmis T. Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016. ACTA ACUST UNITED AC 2016; 23:e605-e614. [PMID: 28050151 DOI: 10.3747/co.23.3394] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.
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Affiliation(s)
- D Bossé
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - T Ng
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - C Ahmad
- Newfoundland and Labrador: Dr. H. Bliss Murphy Cancer Centre, St. John's (Ahmad, Seal, Siddiqui)
| | - A Alfakeeh
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - I Alruzug
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - J Biagi
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - J Brierley
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - P Chaudhury
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - S Cleary
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - B Colwell
- Nova Scotia: QEII Health Sciences Centre, Halifax (Colwell, Dorreen, Snow)
| | - C Cripps
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - L A Dawson
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - M Dorreen
- Nova Scotia: QEII Health Sciences Centre, Halifax (Colwell, Dorreen, Snow)
| | - E Ferland
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - P Galiatsatos
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - S Girard
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - S Gray
- New Brunswick: Saint John Regional Hospital, Saint John (Gray)
| | - F Halwani
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - N Kopek
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - A Mahmud
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - G Martel
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - L Robillard
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - B Samson
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - M Seal
- Newfoundland and Labrador: Dr. H. Bliss Murphy Cancer Centre, St. John's (Ahmad, Seal, Siddiqui)
| | - J Siddiqui
- Newfoundland and Labrador: Dr. H. Bliss Murphy Cancer Centre, St. John's (Ahmad, Seal, Siddiqui)
| | - L Sideris
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - S Snow
- Nova Scotia: QEII Health Sciences Centre, Halifax (Colwell, Dorreen, Snow)
| | - M Thirwell
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - M Vickers
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - R Goodwin
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - R Goel
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - T Hsu
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - E Tsvetkova
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - B Ward
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - T Asmis
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
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Chen R, Gan Y, Ge N, Chen Y, Wang Y, Zhang B, Wang Y, Ye S, Ren Z. Transarterial Chemoembolization versus Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma after Resection within Barcelona Clinic Liver Cancer Stage 0/A: A Retrospective Comparative Study. J Vasc Interv Radiol 2016; 27:1829-1836. [PMID: 27553917 DOI: 10.1016/j.jvir.2016.06.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 06/09/2016] [Accepted: 06/13/2016] [Indexed: 02/07/2023] Open
Abstract
PURPOSE To compare outcomes of transarterial chemoembolization with radiofrequency (RF) ablation in treatment of recurrent hepatocellular carcinoma (HCC) after resection within Barcelona Clinic Liver Cancer (BCLC) stage 0/A. MATERIALS AND METHODS From January 2007 to December 2011, 110 consecutive patients with recurrent HCC meeting BCLC stage 0/A criteria underwent transarterial chemoembolization (n = 78; mean tumor size, 1.9 cm ± 1.0) or RF ablation (n = 32; mean tumor size, 1.9 cm ± 0.6) as initial treatment. The primary outcome was overall survival (OS). Kaplan-Meier method was used to construct survival curves, which were compared by log-rank test. Prognostic factors for OS were analyzed using univariate and multivariate Cox proportional hazard models. RESULTS No significant differences between baseline clinical characteristics of the 2 treatment groups were identified. The 1-, 3-, and 5-year OS rates were 89.7%, 61.0%, and 36.6% for the transarterial chemoembolization group and 90.1%, 72.8%, and 60.0% for the RF ablation group. There was no significant difference in OS rates between the groups (P = .159). Subgroup analysis indicated that RF ablation achieved better survival than transarterial chemoembolization among patients ≤ 55 years old and patients with BCLC stage 0 (P = .036 and P = .045). Multivariate analysis revealed that serum albumin (≤ 35 g/L) (hazard ratio = 2.797; 95% confidence interval, 1.366-2.726; P = .005) and α-fetoprotein (> 400 ng/mL) (HR = 2.336; 95% CI, 1.210-4.508; P = .011) levels before treatment were 2 significant risk factors for poor prognosis. CONCLUSIONS Transarterial chemoembolization might provide a similar OS as RF ablation in patients with recurrent BCLC stage A HCC. However, RF ablation could provide better OS in patients with recurrent BCLC stage 0 HCC.
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Affiliation(s)
- Rongxin Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China
| | - Yuhong Gan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China
| | - Ninglin Ge
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China
| | - Yi Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China
| | - Yan Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China
| | - Boheng Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China
| | - Yanhong Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China
| | - Shenglong Ye
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China
| | - Zhenggang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China.
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Bellissimo F, Pinzone MR, Cacopardo B, Nunnari G. Diagnostic and therapeutic management of hepatocellular carcinoma. World J Gastroenterol 2015; 21:12003-12021. [PMID: 26576088 PMCID: PMC4641121 DOI: 10.3748/wjg.v21.i42.12003] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 08/03/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemo-embolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines.
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Transarterial bland versus chemoembolization for hepatocellular carcinoma: rethinking a gold standard. J Surg Res 2015; 200:552-9. [PMID: 26507276 DOI: 10.1016/j.jss.2015.09.034] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 08/25/2015] [Accepted: 09/25/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Transarterial chemoembolization (TACE) is the most common procedure for the treatment of hepatocellular carcinoma (HCC). However, HCC is generally considered chemoresistant and data demonstrating the superiority of TACE over bland embolization (TAE) are lacking. MATERIALS AND METHODS A nationwide, retrospective cohort study of HCC patients treated with first-line TACE or TAE within the Veterans Affairs health care system (2005-2012) was performed. The primary outcome was overall survival. Risk of death by treatment type (TACE or TAE) was evaluated using multivariate (adjusted for age, presence of cirrhosis, Barcelona Clinic Liver Cancer stage, and Charlson comorbidity score) and propensity score-adjusted Cox regression. RESULTS The cohort included 405 patients treated with first-line transarterial embolization. Among these patients, 32 (7.9%) underwent TAE. Most of the patients (76.8%) had intermediate or advanced stage at presentation. Similar proportions of patients (TACE 53.3% versus TAE 43.7%; P = 0.30) received more than one embolization procedure. There was no difference in median survival (20.1 versus 23.1 mo, respectively; log-rank P = 0.84). Compared to TACE, there was no difference in risk of death associated with TAE after multivariate (hazard ratio [HR] 0.92; 95% CI, 0.61-1.37) and propensity score adjustment (HR = 0.86; 95% CI = 0.58-1.29). CONCLUSIONS There is no clear benefit associated with chemotherapy infusion over bland embolization for HCC treatment. Given the rising incidence of HCC in the United States and considering the added costs associated with TACE compared to TAE, future work comparing these competing management strategies is needed.
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Slotta JE, Kollmar O, Ellenrieder V, Ghadimi BM, Homayounfar K. Hepatocellular carcinoma: Surgeon's view on latest findings and future perspectives. World J Hepatol 2015; 7:1168-1183. [PMID: 26019733 PMCID: PMC4438492 DOI: 10.4254/wjh.v7.i9.1168] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 11/14/2014] [Accepted: 03/20/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver-derived malignancy with a high fatality rate. Risk factors for the development of HCC have been identified and are clearly described. However, due to the lack of tumor-specific symptoms, HCC are diagnosed at progressed tumor stages in most patients, and thus curative therapeutic options are limited. The focus of this review is on surgical therapeutic options which can be offered to patients with HCC with special regard to recent findings, not exclusively focused on surgical therapy, but also to other treatment modalities. Further, potential promising future perspectives for the treatment of HCC are discussed.
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