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1
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Kraj L, Chmiel P, Gryziak M, Grabowska-Derlatka L, Szymański Ł, Wysokińska E. Impact of Thrombocytopenia on Survival in Patients with Hepatocellular Carcinoma: Updated Meta-Analysis and Systematic Review. Cancers (Basel) 2024; 16:1293. [PMID: 38610973 PMCID: PMC11011012 DOI: 10.3390/cancers16071293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 03/24/2024] [Accepted: 03/25/2024] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND Platelets (PLT) have a role in the pathogenesis, progression, and prognosis of hepatocellular carcinoma (HCC) and could represent a readily measurable laboratory parameter to enhance the comprehensive evaluation of HCC patients. METHODS The PubMed, Web of Science, and Scopus databases were searched with a focus on survival as well as patient and tumor-specific characteristics in correlation to reported PLT counts. Survival outcomes were analyzed with both common-effect and random-effects models. The hazard ratio (HR) and its 95% confidence interval (CI) from analyzed trials were incorporated. Studies that did not provide survival data but focused on platelet count correlation with HCC characteristics were reviewed. RESULTS In total, 26 studies, including a total of 9403 patients, met our criteria. The results showed that thrombocytopenia in HCC patients was associated with poor overall survival (common-effect HR = 1.15, 95% CI: 1.06-1.25; random-effect HR = 1.30, 95% CI: 1.05-1.63). Moreover, three studies reveal significant correlations between PLT indices and tumor characteristics such as size, foci number, and etiology of HCC development. CONCLUSION Our meta-analysis confirmed that PLT count could act as a prognostic marker in HCC, especially with a PLT count cut off <100 × 103/mm3. Further prospective studies focusing on the role of PLT in clearly defined subgroups are necessary.
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Affiliation(s)
- Leszek Kraj
- Department of Oncology, University Clinical Centre, Medical University of Warsaw, 02-091 Warsaw, Poland
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Science, 01-447 Magdalenka, Poland;
| | - Paulina Chmiel
- University Clinical Centre, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Maciej Gryziak
- Department of Oncology, University Clinical Centre, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Laretta Grabowska-Derlatka
- 2nd Department of Clinical Radiology, University Clinical Centre, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Łukasz Szymański
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Science, 01-447 Magdalenka, Poland;
| | - Ewa Wysokińska
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL 32224, USA
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Chang PY, Lee RC, Liang PC, Liu YS, Chuang VP, Wu DK, Cheng YF, Huang JI, Tseng HS, Hung CF, Wu RH, Chern MC, Cheng HM, Wu CH, Cheng SM, Chiang CL, Liang HL. Multidisciplinary Taiwan consensus for the use of conventional TACE in hepatocellular carcinoma treatment. Front Oncol 2023; 13:1186674. [PMID: 37427137 PMCID: PMC10328116 DOI: 10.3389/fonc.2023.1186674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as "conventional TACE" (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.
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Affiliation(s)
- Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Yi-Sheng Liu
- Department of Medical Imagine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Vicent P. Chuang
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Ding-Kwo Wu
- Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jen-I. Huang
- Department of Radiology, Tungs’ Taichung Metroharbor Hospital, Taichung, Taiwan
| | - Hsiuo-Shan Tseng
- Department of Radiology, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Chien-Fu Hung
- Department of Radiology, Chang−Gung Memorial Hospital, Taoyuan, Taiwan
| | - Reng-Hong Wu
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Chih Chern
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Hua-Ming Cheng
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chih-Horng Wu
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - She-Meng Cheng
- Department of Radiology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chia-Ling Chiang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Choudhary HB, Mandlik SK, Mandlik DS. Role of p53 suppression in the pathogenesis of hepatocellular carcinoma. World J Gastrointest Pathophysiol 2023; 14:46-70. [PMID: 37304923 PMCID: PMC10251250 DOI: 10.4291/wjgp.v14.i3.46] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/19/2023] [Accepted: 05/31/2023] [Indexed: 06/01/2023] Open
Abstract
In the world, hepatocellular carcinoma (HCC) is among the top 10 most prevalent malignancies. HCC formation has indeed been linked to numerous etiological factors, including alcohol usage, hepatitis viruses and liver cirrhosis. Among the most prevalent defects in a wide range of tumours, notably HCC, is the silencing of the p53 tumour suppressor gene. The control of the cell cycle and the preservation of gene function are both critically important functions of p53. In order to pinpoint the core mechanisms of HCC and find more efficient treatments, molecular research employing HCC tissues has been the main focus. Stimulated p53 triggers necessary reactions that achieve cell cycle arrest, genetic stability, DNA repair and the elimination of DNA-damaged cells’ responses to biological stressors (like oncogenes or DNA damage). To the contrary hand, the oncogene protein of the murine double minute 2 (MDM2) is a significant biological inhibitor of p53. MDM2 causes p53 protein degradation, which in turn adversely controls p53 function. Despite carrying wt-p53, the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway. High p53 in-vivo expression might have two clinical impacts on HCC: (1) Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways; and (2) Exogenous p53 makes HCC susceptible to various anticancer drugs. This review describes the functions and primary mechanisms of p53 in pathological mechanism, chemoresistance and therapeutic mechanisms of HCC.
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Affiliation(s)
- Heena B Choudhary
- Department of Pharmacology, BVDU, Poona College of Pharmacy, Pune 411038, Maharashtra, India
| | - Satish K Mandlik
- Department of Pharmaceutics, BVDU, Poona College of Pharmacy, Pune 411038, Maharashtra, India
| | - Deepa S Mandlik
- Department of Pharmacology, BVDU, Poona College of Pharmacy, Pune 411038, Maharashtra, India
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Liu J, Zhang J, Wang Y, Shu G, Lou C, Du Z. HAIC versus TACE for patients with unresectable hepatocellular carcinoma: A systematic review and meta-analysis. Medicine (Baltimore) 2022; 101:e32390. [PMID: 36595819 PMCID: PMC9794325 DOI: 10.1097/md.0000000000032390] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 12/02/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Hepatic arterial infusion chemotherapy (HAIC) and Transarterial chemoembolization (TACE) both showed good local efficacy in advanced or unresectable hepatocellular carcinoma (HCC). We performed a systematic review and meta-analysis to compare the effect of HAIC with TACE in patients with unresectable HCC. METHODS Clinical trials, which were about HAIC or TACE in Patients with unresectable HCC, were identified by searching PubMed, Medline, and EMBASE from January 2010 to March 2022. A meta-analysis was performed to analyze HAIC in comparison with TACE. Treatment response, 1-year overall survival (OS), 2-year OS and serious adverse events were evaluated in this meta-analysis. RESULTS This meta-analysis included 6 studies. Objective response rate or Partial response in the HAIC group was significantly more than that in the TACE group (P < .05). But, stable disease showed no difference between the 2 groups (P = .52). Disease control rate in the HAIC group was better than that in the TACE group (P < .05). Progressive disease in the HAIC group was less than that in the TACE group (P < .05). In 1-year OS, there was no significant deterioration between the 2 groups (P = .53). There was not significant difference in 2-year OS between the 2 groups (P = .05). serious adverse events in the HAIC group was significantly less than that in the TACE group (P < .05). CONCLUSION To some degree, HAIC may be a better therapeutic method in patients with unresectable HCC than TACE.
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Affiliation(s)
- Junguo Liu
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Jinjuan Zhang
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Yijun Wang
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Guiming Shu
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Cheng Lou
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Zhi Du
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
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Aramaki O, Takayama T, Moriguchi M, Sakamoto H, Yodono H, Kokudo N, Yamanaka N, Kawasaki S, Sasaki Y, Kubota K, Otsuji E, Tanaka S, Matsuyama Y, Fujii M. Arterial chemoembolisation with cisplatin versus epirubicin for hepatocellular carcinoma (ACE 500 study): A multicentre, randomised controlled phase 2/3 trial. Eur J Cancer 2021; 157:373-382. [PMID: 34563992 DOI: 10.1016/j.ejca.2021.08.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 08/06/2021] [Accepted: 08/19/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND Transarterial chemoembolisation (TACE) is a treatment option for hepatocellular carcinoma (HCC), but the optimum agent for TACE remains unclear. We compared the efficacy of TACE with cisplatin versus with epirubicin in patients with unresectable HCC. METHODS This multicentre, randomised, phase 2/3 trial was performed at 21 hospitals in Japan. Patients with liver-confined HCC, performance status 0-2, and Child-Pugh class A/B were randomised to receive TACE with cisplatin or epirubicin. Patients were stratified in accordance with the institution, Child-Pugh class, tumour size, tumour thrombosis, α-fetoprotein and prior treatment. The primary end-point was overall survival in the intention-to-treat population. Tumour response was evaluated in accordance with the Response evaluation criteria in solid tumours criteria. FINDINGS Between 2008 and 2012, 455 patients were randomly assigned to undergo TACE with cisplatin (n = 228) or epirubicin (n = 227). Eleven patients were ineligible, and 444 patients were included in the full analysis. Twelve patients not receiving TACE were excluded, and 432 patients were included in the safety analysis set. In phase 2, disease control rates in cisplatin (91·7%) and epirubicin (91·8%) groups exceeded the predefined threshold of 70%, and the study proceeded to phase 3. After a median follow-up of 32·7 months (IQR = 15·3-49·3), median overall survival periods were 2·93 years (95% CI 2·60-3·79) and 2·74 years (95%CI 2·26-3·21), respectively (hazard ratio 0·90 [95% CI 0·71-1·15], p = 0·22). Median times to treatment failure were 1·38 and 1·46 years (hazard ratio 1·09 [95% CI 0·88-1·35], p = 0·88), response rates were 65·3% and 60·6% (p = 0·31), and serious adverse event rates were 49·8% and 48·3% (p = 0·56), respectively. No treatment-related deaths occurred in either group. INTERPRETATION In our phase 2/3 randomised trial, cisplatin is not significantly superior to epirubicin in TACE for patients with HCC.
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Affiliation(s)
- Osamu Aramaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
| | - Masamichi Moriguchi
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Hidemori Sakamoto
- Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki, Japan
| | - Hiraku Yodono
- Department of Radiology, Narumi Hospital, Hirosaki, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, University of Tokyo, Tokyo, Japan
| | | | - Seiji Kawasaki
- Department of Hepato-Biliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yo Sasaki
- Department of Surgery, Yao Municipal Hospital, Osaka, Japan
| | - Keiichi Kubota
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shinji Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | | | - Masashi Fujii
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
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Cai Z, He C, Zhao C, Lin X. Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma. Front Oncol 2021; 11:611118. [PMID: 33868997 PMCID: PMC8047640 DOI: 10.3389/fonc.2021.611118] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 03/18/2021] [Indexed: 12/30/2022] Open
Abstract
Background Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis and 40%-60% of patients present with advanced disease at the time of diagnosis. Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have recently been used in unresectable ICC. The aim of this study was to compare the survival differences of unresectable ICC patients after TACE and HAIC treatment. Methods Between March 2011 and October 2019, a total of 126 patients with unresectable ICC, as evident from biopsies and imaging, and who had received TACE or HAIC were enrolled in this study. Baseline characteristics and survival differences were compared between the TACE and HAIC treatment groups. Results ICC Patients had significantly higher survival rates after the HAIC treatment, compared with those after TACE treatment [1-year overall survival (OS) rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P=0.028; 1-year progression-free survival (PFS) rates: 15.0% vs. 20.0%, 2-year PFS rates: 0% vs. 0%, P=0.641; 1-year only intrahepatic PFS (OIPFS) rates: 35.0% vs. 24.4%, 2-year OIPFS rates: 13.1% vs. 14.6%, P = 0.026]. Multivariate Cox regression analysis showed that HAIC was a significant and independent factor for OS and OIPFS in the study cohort. Conclusions HAIC is superior to TACE for treatment of unresectable ICC. A new tumor response evaluation procedure for HAIC treatment in unresectable ICC patients is needed to provide better therapeutic strategies. A randomized clinical trial comparing the survival benefits of HAIC and TACE is therefore being considered.
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Affiliation(s)
- Zhiyuan Cai
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Chaobin He
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chongyu Zhao
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaojun Lin
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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Kloeckner R, Galle PR, Bruix J. Local and Regional Therapies for Hepatocellular Carcinoma. Hepatology 2021; 73 Suppl 1:137-149. [PMID: 32557715 DOI: 10.1002/hep.31424] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 05/21/2020] [Accepted: 05/26/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Peter Robert Galle
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, CIBEREHD Barcelona, Barcelona, Spain
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Becker LS, Maschke SK, Dewald CLA, Meine TC, Winther HBM, Kirstein MM, Kloeckner R, Meyer BC, Wacker F, Hinrichs JB. Two-dimensional parametric parenchymal blood flow in transarterial chemoembolisation for hepatocellular carcinoma: perfusion change quantification and tumour response prediction at 3 months post-intervention. Clin Radiol 2020; 76:160.e27-160.e33. [PMID: 33028487 DOI: 10.1016/j.crad.2020.09.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 09/09/2020] [Indexed: 11/19/2022]
Abstract
AIM To evaluate the feasibility and potential value of two-dimensional (2D) parametric parenchymal blood flow (2D-PPBF) for the assessment of perfusion changes during transarterial chemoembolisation with drug-eluting beads (DEB-TACE) and to analyse correlations of 2D-PPBF parameters and tumour response. MATERIALS AND METHODS Thirty-two patients (six women, 26 men, mean age: 67±8.9 years) with unresectable hepatocellular carcinoma (HCC) who underwent their first DEB-TACE were included in this study. To quantify perfusion changes using 2D-PPBF, the acquired digital subtraction angiography (DSA) series were post-processed. Ratios were calculated between the reference region of interest (ROI) and the wash-in rate (WIR), the arrival to peak (AP) and the area under the curve (AUC) of the generated time-density curves. Comparisons between pre- and post-embolisation data were made using the Wilcoxon signed-rank test. Tumour response was assessed at 3 months using the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and correlated to changes of 2D-PPBF parameters. RESULTS All 2D-PPBF parameters derived from the ROI-based time-attenuation curves were significantly different pre-versus post-DEB-TACE. Although the AUC, the WIR and target lesion size measured in accordance with mRECIST decreased (p≤0.0001) significantly, AP values showed a significant increase (p = 0.0033). Tumour response after DEB-TACE correlated with changes in the AUC (p = 0.01, r = -0.45). CONCLUSION 2D-PPBF offers an objective approach to analyse perfusion changes of embolised tumour tissue following DEB-TACE and can therefore be used to predict tumour response.
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Affiliation(s)
- L S Becker
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - S K Maschke
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - C L A Dewald
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - T C Meine
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - H B M Winther
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - M M Kirstein
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - R Kloeckner
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Centre, Mainz, Germany
| | - B C Meyer
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - F Wacker
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - J B Hinrichs
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.
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Wang B, Li F, Cheng L, Zhan Y, Wu B, Chen P, Shen J, Wu W, Ma X, Zhu J, Pan B, Guo W, Cheng Y. The pretreatment platelet count is an independent predictor of tumor progression in patients undergoing transcatheter arterial chemoembolization with hepatitis B virus-related hepatocellular carcinoma. Future Oncol 2019; 15:827-839. [PMID: 30714399 DOI: 10.2217/fon-2018-0591] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Aim: To explore the prognostic value of the pretreatment platelet (PLT) count in patients undergoing transcatheter arterial chemoembolization (TACE) with hepatocellular carcinoma (HCC). Materials & methods: We prospectively analyzed 317 hepatitis B virus-related HCC patients undergoing TACE. Time to progression (TTP) was selected to evaluate the clinical significance of PLT level in HCC patients. Results: PLT was the only parameter showing statistical significance of all the clinical characteristics between two distinct tumor response groups. After ruling out cirrhosis as a potential major confounding factor, the conclusion was further established. Higher pretreatment PLT level, portal vessel invasion and higher stratification of α-fetoprotein level were independently associated with longer TTP. The prognostic score model combining the three risk factors revealed that higher risk scores might mean shorter TTP. Conclusion: The pretreatment PLT level is a potentially useful biomarker to predict the prognostic outcomes in HCC patients undergoing TACE and deserves to be further explored in subsequent works.
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Affiliation(s)
- Beili Wang
- Department of Clinical Laboratory, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Feng Li
- Department of Hematology, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
- Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan Universiy, Shanghai 201700, PR China
| | - Luya Cheng
- Department of Hematology, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Yanxia Zhan
- Department of Hematology, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Boting Wu
- Department of Transfusion Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China
| | - Pu Chen
- Department of Clinical Laboratory, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Junfei Shen
- Department of Clinical Laboratory, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Wenhao Wu
- Department of Clinical Laboratory, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Xiaolu Ma
- Department of Clinical Laboratory, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Jie Zhu
- Department of Clinical Laboratory, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Baishen Pan
- Department of Clinical Laboratory, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Wei Guo
- Department of Clinical Laboratory, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
| | - Yunfeng Cheng
- Department of Hematology, Zhongshan Hospital Fudan University, Shanghai 200032, PR China
- Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan Universiy, Shanghai 201700, PR China
- Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China
- Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Shanghai 200032, PR China
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10
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Lin EY, Lee RC, Guo WY, Wu FCH, Gehrisch S, Kowarschik M. Three-Dimensional Quantitative Color-Coding Analysis of Hepatic Arterial Flow Change during Chemoembolization of Hepatocellular Carcinoma. J Vasc Interv Radiol 2018; 29:1362-1368. [PMID: 30170947 DOI: 10.1016/j.jvir.2018.04.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 03/28/2018] [Accepted: 04/07/2018] [Indexed: 01/15/2023] Open
Abstract
PURPOSE To evaluate feasibility of using three-dimensional (3D) quantitative color-coding analysis (QCA) to quantify substasis endpoints after transcatheter arterial chemoembolization of hepatocellular carcinoma (HCC). MATERIALS AND METHODS This single-institution prospective study included 20 patients with HCC who had undergone segmental or subsegmental transcatheter arterial chemoembolization between December 2015 and March 2017. The chemoembolization endpoint was a sluggish anterograde tumor-feeding arterial flow without residual tumor stains. Contrast medium bolus arrival time (BAT) was used as an indicator of arterial flow. BAT of the proper hepatic artery was obtained as a reference point. BATs of the proximal right lobar artery, proximal left lobar artery, and segmental artery that received embolization were analyzed before and after chemoembolization. Wilcoxon signed rank test was used to evaluate the difference between BATs before and after chemoembolization. RESULTS BATs before and after chemoembolization of the segmental artery that received embolization were 0.47 seconds (interquartile range [IQR], 0.31-0.70 s) and 1.04 seconds (IQR, 0.78-2.01 s; P < .001), respectively. BATs before and after chemoembolization of the proximal left lobar hepatic artery (0.35 s [IQR, 0.11-0.55] and 0.13 s [IQR, 0.05-0.32], P = .025) and right lobar hepatic artery (0.23 s [IQR, 0.13-0.65] and 0.22 s [IQR, 0.08-0.39], P = .027) exhibited no significant change. CONCLUSIONS 3D QCA is a feasible method for quantifying sluggish segmental arterial flow after transcatheter arterial chemoembolization in patients with HCC.
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Affiliation(s)
- Ethan Yiyang Lin
- Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Radiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City 11217, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City 11217, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Wan-Yuo Guo
- Department of Radiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City 11217, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | | | - Sonja Gehrisch
- Advanced Therapies, Siemens Healthcare GmbH, Forchheim, Germany
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Liu Q, Fan D, Adah D, Wu Z, Liu R, Yan QT, Zhang Y, Du ZY, Wang D, Li Y, Bao SY, Liu LP. CRISPR/Cas9‑mediated hypoxia inducible factor‑1α knockout enhances the antitumor effect of transarterial embolization in hepatocellular carcinoma. Oncol Rep 2018; 40:2547-2557. [PMID: 30226584 PMCID: PMC6151876 DOI: 10.3892/or.2018.6667] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Accepted: 07/31/2018] [Indexed: 12/15/2022] Open
Abstract
Transarterial embolization (TAE) is a palliative option commonly used for the treatment of advanced, unresectable hepatocellular carcinoma (HCC). However, patient prognosis in regards to overall survival has not improved with this method, mainly due to hypoxia-inducible factor-1α (HIF-1α)-induced angiogenesis and invasiveness. Thus, it is hypothesized that HIF-1α may be an ideal knockout target for the treatment of HCC in combination with TAE. Thus, in the present study, HIF-1α knockout was conducted in human liver cancer SMMC-7721 cells and a xenograft HCC model was established using a lentivirus-mediated CRISPR/Cas system (LV-Cas) with small guide RNA-721 (LV-H721). Furthermore, hepatic artery ligation (HAL) was used to mimic human transarterial chemoembolization in mice. The results revealed that HIF-1α was highly expressed in both HCC patient tissues and SMMC-7721-induced tumor tissues. The HIF-1α knockout in SMMC-7721 cells significantly suppressed cell invasiveness and migration, and induced cell apoptosis under CoCl2-mimicking hypoxic conditions. Compared with the control groups, HAL + LV-H721 inhibited SMMC-7721 tumor growth in orthotopic HCC and markedly prolonged the survival of HCC-bearing mice, which was accompanied by a lower CD31 expression (tumor angiogenesis) and increased apoptosis in the tumor cells. These findings demonstrated a valuable antitumor synergism in combining CRISPR/Cas9-mediated HIF-1α knockout with TAE in mice and highlighted the possibility that HIF-1α may be an effective therapeutic knockout target in combination with TAE for HCC treatment.
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Affiliation(s)
- Quan Liu
- Department of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
| | - Dahua Fan
- Department of Chinese and Western Integrative Medicine, The Eighth Affiliated Hospital of Sun Yat‑Sen University, Shenzhen, Guangdong 518033, P.R. China
| | - Dickson Adah
- University of Chinese Academy of Sciences, Beijing 100049, P.R. China
| | - Zhengzhi Wu
- Department of Chinese and Western Integrative Medicine, The Eighth Affiliated Hospital of Sun Yat‑Sen University, Shenzhen, Guangdong 518033, P.R. China
| | - Renyan Liu
- Department of Pharmacology, Upstate Medical University, State University of New York, Syracuse, NY 13210, USA
| | - Qiao-Ting Yan
- Department of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
| | - Yue Zhang
- Department of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
| | - Zhi-Yong Du
- Department of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
| | - Dou Wang
- Department of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
| | - Yan Li
- Department of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
| | - Shi-Yun Bao
- Department of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
| | - Li-Ping Liu
- Department of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
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12
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Maschke SK, Werncke T, Klöckner R, Rodt T, Renne J, Kirstein MM, Vogel A, Wacker FK, Meyer BC, Hinrichs JB. Quantification of perfusion reduction by using 2D-perfusion angiography following transarterial chemoembolization with drug-eluting beads. Abdom Radiol (NY) 2018; 43:1245-1253. [PMID: 28840307 DOI: 10.1007/s00261-017-1296-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE To analyze the feasibility of 2D-perfusion angiography (2D-PA) for the quantification of perfusion reduction following transarterial chemoembolization with drug-eluting beads (DEB-TACE). METHODS Overall, 24 DEB-TACE procedures in 19 patients were included. To quantify changes in tumor perfusion following DEB-TACE using 2D-PA, the acquired digital subtraction angiography (DSA) series were post-processed. A reference region-of-interest (ROI) in a main hepatic artery and two, distal target ROIs in embolized tumor tissue and in non-target liver parenchyma were placed in corresponding areas on DSA pre- and post-DEB-TACE. The time to peak (TTP), peak density (PD), and the area under the curve (AUC) were assessed and the ratios reference ROI/target ROIs were calculated. RESULTS In the embolized tumor, the 2D-PA ratios changed significantly (p < 0.05) after DEB-TACE, whereas no significant change was observed for non-target liver parenchyma (p > 0.05). PDtumor/PDinflow differed significantly to PDparenchyma/PDinflow pre-DEB-TACE (p < 0.0001), likewise AUCtumor/AUCinflow to AUCparenchyma/AUCinflow (p < 0.0001) with higher values in tumor tissue. The post-DEB-TACE ratios of AUC decreased significantly in the tumor tissue compared to the non-target liver parenchyma (p < 0.05). CONCLUSION 2D-PA offers an objective approach to quantify the immediate perfusion reduction of embolized tumor tissue following DEB-TACE and may therefore be used to monitor peri-interventional stasis and to quantify technical success.
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Affiliation(s)
- Sabine K Maschke
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Thomas Werncke
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Roman Klöckner
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Centre, Mainz, Germany
| | - Thomas Rodt
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Julius Renne
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Martha M Kirstein
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Frank K Wacker
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Bernhard C Meyer
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Jan B Hinrichs
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
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Liu X, Wang Z, Chen Z, Liu L, Ma L, Dong L, Zhang Z, Zhang S, Yang L, Shi J, Fan J, Wang X, Gao Q. Efficacy and Safety of Transcatheter Arterial Chemoembolization and Transcatheter Arterial Chemotherapy Infusion in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Oncol Res 2017; 26:231-239. [PMID: 28911342 PMCID: PMC7844720 DOI: 10.3727/096504017x15051752095738] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a worldwide health threat with increasing incidence and a high mortality rate. Most HCC patients are diagnosed at an advanced stage and are unable to undergo potential curative surgery. Transcatheter arterial chemoembolization (TACE) and transcatheter arterial chemotherapy infusion (TACI) are two of the main palliative treatments for advanced HCC patients. The clinical efficacy and safety of TACE and TACI are controversial. For this reason, we conducted a systematic review and meta-analysis to summarize the current evidence. We searched for randomized controlled trials (RCTs) and cohort studies that compared the clinical outcomes and adverse effects in HCC patients who received TACE or TACI treatments. The database search was performed and last updated on November 1, 2016. Overall survival and clinical response were compared using a hazard ratio (HR) with a 95% confidence interval (CI). A total of 11 clinical studies that included 13,090 patients were included based on the inclusion/exclusion criteria, of which 9 were cohort studies and 2 were RCTs. TACE was associated with a 23% lower hazard of death compared to TACI (pooled HR = 0.77, 95% CI = 0.67–0.88, p = 0.0002). Patients receiving TACE had a 28% higher disease control rate (DCR) and 162% higher objective response rate (ORR). Only the increase in ORR associated with TACE was statistically significant [DCR: odds ratio (OR) = 1.28, 95% CI = 0.35–4.64, p = 0.71; ORR: OR = 2.62, 95% CI = 1.33–5.15, p = 0.002]. TACE is associated with more favorable survival and response rate than TACI in patients with intermediate or advanced HCC.
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Affiliation(s)
- Xinyang Liu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Zhichao Wang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Zongwei Chen
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Longzi Liu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Lijie Ma
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Liangqing Dong
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Zhao Zhang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Shu Zhang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Liuxiao Yang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Jieyi Shi
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Jia Fan
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Xiaoying Wang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
| | - Qiang Gao
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
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14
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Zhao J, Li D, Shi Y, Shi F, Feng C, Li W, Tao M, Liang R. Transarterial Infusion Chemotherapy With and Without Embolisation in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2017. [DOI: 10.47102/annals-acadmedsg.v46n5p174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Introduction: The purpose of this meta-analysis was to compare the efficacy of transarterial chemoembolisation (TACE) and iodised oil infusion chemotherapy without embolisation (TAI) in patients with hepatocellular carcinoma. Materials and Methods: We searched for randomised controlled trials, retrospective cohort studies, and two-arm prospective studies that compared the clinical outcomes in patients who received TACE and TAI treatment. Database search was performed through 14 December 2016. Rates of survival and therapy response were compared using odds ratios (OR) with 95% confidence intervals (CI). Results: Survival rates and therapy response rates were similar between patients who received TACE and TAI treatments (pooled OR: 1.278; 95% CI , 0.783 to 2.086, P = 0.327; and pooled OR: 1.502; 95% CI, 0.930 to 2.426, P = 0.096, respectively). Conclusion: Our results suggest that treatment intensification by adding embolisation did not increase overall survival and therapy response over TAI in patients with hepatocellular carcinoma.
Key words: Liver cancer, Liver disease, Transarterial chemoembolisation
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Affiliation(s)
- Jing Zhao
- The Affiliated Hospital of Soochow University, People’s Republic of China
| | - Dapeng Li
- The Affiliated Hospital of Soochow University, People’s Republic of China
| | - Yue Shi
- The Affiliated Hospital of Soochow University, People’s Republic of China
| | - Fengling Shi
- The Affiliated Hospital of Soochow University, People’s Republic of China
| | - Chengting Feng
- The Affiliated Hospital of Soochow University, People’s Republic of China
| | - Wei Li
- The Affiliated Hospital of Soochow University, People’s Republic of China
| | - Min Tao
- The Affiliated Hospital of Soochow University, People’s Republic of China
| | - Rongrui Liang
- The Affiliated Hospital of Soochow University, People’s Republic of China
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15
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Quantitative Real-Time Fluoroscopy Analysis on Measurement of the Hepatic Arterial Flow During Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma: Comparison with Quantitative Digital Subtraction Angiography Analysis. Cardiovasc Intervent Radiol 2016; 39:1557-1563. [DOI: 10.1007/s00270-016-1421-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 07/07/2016] [Indexed: 11/25/2022]
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Wang J, Cheng JJ, Huang KY, Zhuang ZG, Zhang XB, Chi JC, Hua XL, Xu JR. Quantitative assessment of angiographic perfusion reduction using color-coded digital subtraction angiography during transarterial chemoembolization. Abdom Radiol (NY) 2016; 41:545-52. [PMID: 27039326 DOI: 10.1007/s00261-015-0622-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE The aim of this study was to develop a quantitative measurement of perfusion reduction using color-coded digital subtraction angiography (ccDSA) to monitor intra-procedural arterial stasis during TACE. MATERIALS AND METHODS A total number of 35 patients with hepatocellular carcinoma who had undergone TACE were enrolled into the study. Pre- and post-two-dimensional digital subtraction angiography scans were conducted with same protocol and post-processed with ccDSA prototype software. Time-contrast-intensity (CI[t]) curve was obtained by region-of-interest (ROI) measurement on the generated ccDSA image. Quantitative 2D perfusion parameters time to peak, area under the curve (AUC), maximum upslope, and contrast intensity peak (CI-Peak) derived from the ROI-based CI[t] curve for pre- and post-TACE were evaluated to assess the reduction of antegrade blood flow and tumor blush. Relationships between 2D perfusion parameters, subjective angiographic chemoembolization endpoint (SACE) scale, and clinical outcomes were analyzed. RESULTS Area normalized AUC and CI-Peak revealed significant reduction after the TACE (P < 0.0001). AUCnorm decreased from pre-procedure of 0.867 ± 0.242 to 0.421 ± 0.171 (P < 0.001) after completion of TACE. CI-Peaknorm was 0.739 ± 0.221 before TACE and 0.421 ± 0.174 (P < 0.001) after TACE. Tumor blood supply time slowed down obviously after embolization. A perfusion reduction either from AUCnorm or CI-Peaknorm ranging from 30% to 40% was associated with SACE level III and a reduction ranging from 60% to 70% was equivalent to SACE level IV. For intermediate reduction (SACE level III), better tumor response was found after TACE rather than a higher reduction (SACE level IV). CONCLUSION ccDSA application provides an objective approach to quantify the perfusion reduction and subjectively evaluate the arterial stasis of antegrade blood flow and tumor blush caused by TACE.
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Affiliation(s)
- Ji Wang
- Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Rd. 160, Shanghai, 200127, China
| | - Jie-Jun Cheng
- Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Rd. 160, Shanghai, 200127, China
| | - Kai-Yi Huang
- Siemens Limited China, Shanghai Branch, Zhouzhu Rd. 278, Shanghai, 201318, China
| | - Zhi-Guo Zhuang
- Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Rd. 160, Shanghai, 200127, China
| | - Xue-Bin Zhang
- Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Rd. 160, Shanghai, 200127, China
| | - Jia-Chang Chi
- Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Rd. 160, Shanghai, 200127, China
| | - Xiao-Lan Hua
- Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Rd. 160, Shanghai, 200127, China
| | - Jian-Rong Xu
- Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Rd. 160, Shanghai, 200127, China.
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Development of Conventional Transarterial Chemoembolization for Hepatocellular Carcinomas in Japan: Historical, Strategic, and Technical Review. AJR Am J Roentgenol 2015; 205:764-73. [DOI: 10.2214/ajr.15.14825] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Gao S, Zhang PJ, Guo JH, Chen H, Xu HF, Liu P, Yang RJ, Zhu X. Chemoembolization alone vs combined chemoembolization and hepatic arterial infusion chemotherapy in inoperable hepatocellular carcinoma patients. World J Gastroenterol 2015; 21:10443-10452. [PMID: 26420971 PMCID: PMC4579891 DOI: 10.3748/wjg.v21.i36.10443] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 07/13/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To compare the efficacy and safety of chemoembolization alone or chemoembolization combined with hepatic arterial infusion chemotherapy (HAIC), including oxaliplatin (OXA), 5-fluorouracil (5-FU) and folinic acid (CF), in inoperable hepatocellular carcinoma (HCC) without distant metastasis. METHODS Eighty-four inoperable HCC patients were enrolled. Thirty-nine patients underwent chemoembolization alone, and the other 45 patients underwent chemoembolization + HAIC (OXA/5-FU/CF) treatment non-randomly. The progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse reactions were compared between the two groups. RESULTS A significant difference in the ORR was observed between the chemoembolization alone and chemoembolization + HAIC groups. There was no statistically significant difference in DCR between the two groups. The median PFS (mPFS) showed a significant difference between the two groups. For patients with BCLC stage A/B disease, with or without vessel invasion, the chemoembolization + HAIC group showed better mPFS when compared to chemoembolization alone, but no significant difference was found in patients with BCLC stage C disease. The parameter of pain (grade III-IV) in the chemoembolization + HAIC group was increased statistically. CONCLUSION Chemoembolization combined with HAIC with OXA/5-FU/CF may be safe and more effective than chemoembolization alone for inoperable HCC patients without distant metastasis.
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Pang Q, Qu K, Zhang JY, Song SD, Liu SS, Tai MH, Liu HC, Liu C. The Prognostic Value of Platelet Count in Patients With Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Medicine (Baltimore) 2015; 94:e1431. [PMID: 26376382 PMCID: PMC4635796 DOI: 10.1097/md.0000000000001431] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Thrombocytopenia has been acknowledged to be a crucial risk factor for cirrhosis formation and hepatocarcinogenesis in chronic liver diseases. However, to date, the association between platelet count (PLT) and the prognosis of hepatocellular carcinoma (HCC) remains inconsistent and controversial. The aim of the present study was to determine whether PLT could be used as a useful predictor of survival in patients with HCC. We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2014. Studies were included if a statistical relationship was investigated between PLT and survival for HCC, and hazard ratio (HR) and 95% confidence intervals (CIs) for overall survival (OS) or recurrence-free survival (RFS) were provided. The quality of each included study was assessed by Newcastle-Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did subgrouped and meta-regression analysis. Finally, we identified 33 eligible articles (published from 1998 to 2014) involved 5545 patients by retrieval. A low level of preoperative PLT was found to be significantly associated with a poor survival of HCC. Irrespective of the therapy used, the pooled HRs for OS and RFS were 1.41 (95% CI, 1.14-1.75) and 1.44 (95% CI, 1.13-1.83), respectively. Specifically, in patients who underwent liver resection, the pooled HRs for OS and RFS were 1.67 (95% CI, 1.22-2.27) and 1.44 (95% CI, 1.04-1.99), respectively. Furthermore, patients with preoperative thrombocytopenia (PLT < 100 × 10⁹/L) had a worse OS (HR: 1.73, 95% CI, 1.29-2.32) and RFS (HR: 1.57, 95% CI, 1.31-1.87) in comparison with patients without thrombocytopenia. All our findings showed no significant changes due to the removal of any study or the use of an opposite-effects model, and there was no significant publication bias. The limitations of this meat-analysis were nonuniform cut-off values of PLT, high between-study heterogeneities, potential confounders, and a bias of publication year. A low preoperative PLT level results in an unfavorable outcome in HCC. PLT is a simple, inexpensive, and useful predictor of survival in patients with HCC.
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Affiliation(s)
- Qing Pang
- From the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
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Lin YY, Lee RC, Tseng HS, Liu CA, Guo WY, Chang CY. Objective Measurement of Arterial Flow Before and After Transcatheter Arterial Chemoembolization: A Feasibility Study Using Quantitative Color-Coding Analysis. Cardiovasc Intervent Radiol 2015; 38:1494-501. [DOI: 10.1007/s00270-015-1111-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Accepted: 04/03/2015] [Indexed: 10/23/2022]
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21
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Otsuji K, Takai K, Nishigaki Y, Shimizu S, Hayashi H, Imai K, Suzuki Y, Hanai T, Ideta T, Miyazaki T, Tomita E, Shimizu M, Moriwaki H. Efficacy and safety of cisplatin versus miriplatin in transcatheter arterial chemoembolization and transarterial infusion chemotherapy for hepatocellular carcinoma: A randomized controlled trial. Hepatol Res 2015; 45:514-22. [PMID: 24961745 DOI: 10.1111/hepr.12376] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Revised: 05/11/2014] [Accepted: 06/16/2014] [Indexed: 02/08/2023]
Abstract
AIM Transcatheter arterial chemoembolization (TACE) and transarterial infusion chemotherapy (TAI) are the main therapeutic strategies for treatment of advanced hepatocellular carcinoma (HCC). We conducted a randomized controlled trial to compare the efficacy and safety of cisplatin and miriplatin in TACE and TAI. METHODS Patients with HCC of indication for TACE or TAI were randomly assigned to receive either cisplatin or miriplatin (49 patients per group) between April 2010 and May 2013. The primary end-point was the therapeutic effect (TE) 3 months after initial treatment, and the secondary end-point was overall survival. RESULTS TE could be evaluated in 26 patients of the cisplatin group and 20 patients of the miriplatin group. In the cisplatin group, 11 (42.3%) and 15 (57.7%) patients were classified as showing TE3 + 4 and TE1 + 2, respectively, while in the miriplatin group, each number was nine (45.0%) and 11 (55.0%) (P = 0.8551). Furthermore, no significant difference in overall survival was found between two groups for all patients (P = 0.905) or those treated only with TAI (10 in the cisplatin group and eight in the miriplatin group; P = 0.695). TE3 + 4 group showed better overall survival than TE1 + 2 group (P = 0.0263). Grade 4 or higher adverse event did not occur in either group. Creatinine levels in the cisplatin group rose 3 days after TACE or TAI (P = 0.0397). CONCLUSION Cisplatin and miriplatin had equal efficacy for TACE and TAI, but cisplatin should be avoided for patients with renal dysfunction or inadequate hydration. Good TE improved overall survival.
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Affiliation(s)
- Kentarou Otsuji
- Department of Gastroenterology and Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
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Abstract
Over the last decade, transarterial therapies have gained worldwide acceptance as standard of care for inoperable primary liver cancer. Survival times after transarterial chemoembolization (TACE) continue to improve as the technique and selection criteria are refined. Transarterial treatments, frequently provided in an outpatient setting, are now safely and effectively being applied to patients with even advanced malignancy or partially decompensated cirrhosis. In the coming years, newer transarterial therapies such as radiation segmentectomy, boosted-transarterial radioembolzation, combined TACE-ablation, TACE-portal vein embolization, and transarterial infusion of cancer-specific metabolic inhibitors promise to continue improving survival and quality of life.
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Handa T, Imai Y, Sugawara K, Chikayama T, Nakazawa M, Ando S, Hamaoka K, Inao M, Nakayama N, Mochida S. Transcatheter arterial chemoembolization for hepatocellular carcinoma: Comparison of the therapeutic efficacies between miriplatin and epirubicin. Hepatol Res 2014; 44:1072-80. [PMID: 23957866 DOI: 10.1111/hepr.12225] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Revised: 07/22/2013] [Accepted: 08/12/2013] [Indexed: 02/08/2023]
Abstract
AIM The therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using miriplatin was evaluated in comparison with that using epirubicin in patients with hepatocellular carcinoma (HCC). METHODS Two hundred and eight-nine HCC patients receiving TACE were retrospectively enrolled; none of the patients gave a previous TACE history. The short-term therapeutic efficacy was evaluated by computed tomography (CT) performed 1 month later. In patients showing TE-4, CT and/or magnetic resonance imaging examinations were performed repeatedly and the long-term therapeutic efficacy was assessed based on local tumor recurrence. RESULTS After exclusion of 68 patients (CT not performed at 1 month), 97 patients treated with epirubicin and 124 treated with miriplatin were analyzed. The percentage of patients showing TE-4 was 46.8% in the miriplatin-TACE group, being significantly higher than that in the epirubicin-TACE group (33.0%). The cumulative local recurrence rates at 18 months were 71.2% in the miriplatin-TACE group and 43.1% in the epirubicin-TACE group; multivariate analysis revealed higher local tumor recurrence rates in the miriplatin-TACE group than in the epirubicin-TACE group. CONCLUSION For HCC patients, although miriplatin-TACE was superior to epirubicin-TACE in the short term, it proved inferior to the latter in the long term. The merits of TACE using miriplatin should be further investigated, because adverse effects appear to be minimal after miriplatin administration.
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Affiliation(s)
- Takahiro Handa
- Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyamacho, Saitama, Japan
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Matsumoto T, Endo J, Hashida K, Ichikawa H, Kojima S, Takashimizu S, Watanabe N, Yamagami T, Hasebe T. Balloon-occluded transarterial chemoembolization using a 1.8-French tip coaxial microballoon catheter for hepatocellular carcinoma: technical and safety considerations. MINIM INVASIV THER 2014; 24:94-100. [PMID: 25263680 DOI: 10.3109/13645706.2014.951657] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To evaluate the technical feasibility and safety considerations of balloon-occluded transarterial chemoembolization (B-TACE) using a newly developed 1.8-French (Fr) tip microballoon catheter for hepatocellular carcinoma (HCC). MATERIAL AND METHODS Between February 2013 and May 2013, 31 patients (20 males, 11 females; age range 56-85 years) underwent B-TACE using a 1.8-Fr tip microballoon catheter for unresectable HCC. The technical success rate, procedural complications, and adverse events of B-TACE were retrospectively investigated. RESULTS A total of 31 patients were subjected to 70 sessions of B-TACE using a 1.8-Fr tip microballoon catheter. The level of B-TACE was sub-subsegmental in 11, subsegmental in 35, segmental in 14, lobar in five, and right inferior phrenic artery in five sessions. The overall technical success rate was 99% (69 out of 70 sessions). As procedural complications, rupturing of the microballoon (n = 3) and aneurysmal dilatation at the site of balloon occlusion (n = 2) were encountered. There were no significant differences in any parameters between blood biochemical examination before and between two to four weeks after the procedure. CONCLUSION A 1.8-Fr tip microballoon catheter enables selective catheterization in patients with HCC and B-TACE using the 1.8-Fr tip microballoon catheter is a safe procedure.
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Affiliation(s)
- Tomohiro Matsumoto
- Department of Radiology, Tokai University Hachioji Hospital, Tokai University School of Medicine , Tokyo , Japan
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Park HC, Park HB, Chung CY, Jung MW, Joo YE, Choi SK, Cho SB. Acute Obstructive Cholangitis Complicated by Tumor Migration after Transarterial Chemoembolization: A Case Report and Literature Review. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2014; 63:171-5. [DOI: 10.4166/kjg.2014.63.3.171] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- Hyung Chul Park
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun Bum Park
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Cho Yun Chung
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Min Woo Jung
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Young Eun Joo
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Sung Kyu Choi
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Sung Bum Cho
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
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NISHIKAWA HIROKI, OSAKI YUKIO, KITA RYUICHI, KIMURA TORU, OHARA YOSHIAKI, TAKEDA HARUHIKO, SAKAMOTO AZUSA, SAITO SUMIO, NISHIJIMA NORIHIRO, NASU AKIHIRO, KOMEKADO HIDEYUKI, NISHIGUCHI SHUHEI. Comparison of transcatheter arterial chemoembolization and transcatheter arterial chemotherapy infusion for patients with intermediate-stage hepatocellular carcinoma. Oncol Rep 2013; 31:65-72. [DOI: 10.3892/or.2013.2845] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Accepted: 10/25/2013] [Indexed: 11/06/2022] Open
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Seko Y, Ikeda K, Kawamura Y, Fukushima T, Hara T, Sezaki H, Hosaka T, Akuta N, Suzuki F, Kobayashi M, Suzuki Y, Saitoh S, Arase Y, Kumada H. Antitumor efficacy of transcatheter arterial chemoembolization with warmed miriplatin in hepatocellular carcinoma. Hepatol Res 2013; 43:942-9. [PMID: 23301851 DOI: 10.1111/hepr.12041] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2012] [Revised: 11/11/2012] [Accepted: 12/03/2012] [Indexed: 12/31/2022]
Abstract
AIM Patients with unresectable hepatocellular carcinoma (HCC) often undergo transcatheter arterial chemoembolization (TACE). Miriplatin is a lipophilic cisplatin derivative used in TACE that is effective in HCC. However, the difference in antitumor efficacy between warmed versus room temperature miriplatin is unclear. METHODS Chemotherapy efficacy was evaluated by dynamic computed tomography 1-3 months after TACE, according to the Modified Response Evaluation Criteria in Solid Tumors. A total of 203 patients with HCC who received TACE with miriplatin for the first time were included in a follow-up study to retrospectively investigate its efficacy and safety. Overall, 45 patients underwent TACE with warmed (40°C) miriplatin and 158 patients received TACE with room temperature miriplatin. RESULTS Seventy patients (44.3%) treated with room temperature miriplatin and 32 patients (71.1%) who received warmed miriplatin experienced complete or partial responses. Multivariate analysis identified miriplatin temperature (warmed miriplatin, risk ratio (RR) = 2.26, P = 0.047), tumor number (solitary, RR = 3.48, P = 0.007), α-fetoprotein (AFP) level (<50 ng/mL, RR = 2.35, P = 0.012) and history of TACE (no history, RR = 2.22, P = 0.041) as predictors of objective response following TACE with miriplatin, and no serious complications were observed. CONCLUSION Warm temperature, solitary tumors, low AFP level and first TACE are significant and independent predictors of objective response after TACE using miriplatin. These results suggest that warmed miriplatin can be considered as one of the standard treatments for unresectable HCC.
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Affiliation(s)
- Yuya Seko
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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Kawamura Y, Ikeda K, Fukushima T, Seko Y, Hara T, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H. What Is the Most Effective Drug Delivery System for Cisplatin during the Treatment of Hepatic Tumors with Single-Session Transcatheter Chemotherapy? A Pilot Study. Gut Liver 2013; 7:576-84. [PMID: 24073316 PMCID: PMC3782673 DOI: 10.5009/gnl.2013.7.5.576] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2012] [Revised: 01/07/2013] [Accepted: 01/31/2013] [Indexed: 12/30/2022] Open
Abstract
Background/Aims The aim of this study was to determine the pharmacodynamics of cisplatin following three different treatment procedures for intrahepatic arterial infusion therapy for hepatocellular carcinoma (HCC). Methods We divided 13 HCC patients into the following three groups: group A, lone injection of cisplatin (n=3); group B, combined injection of cisplatin and lipiodol, with embolization using small gelatin cubes (GCs) (n=5); and group C, injection of suspended lipiodol with cisplatin powder, with embolization using small GCs (n=5). In each group, the free cisplatin concentration in the hepatic vein was measured at 0, 5, 10, and 30 minutes. Results The mean free cisplatin concentrations were as follows. For group A, the mean was 48.58 µg/mL at 0 minute, 7.31 µg/mL at 5 minutes, 5.70 µg/mL at 10 minutes, and 7.15 µg/mL at 30 minutes. For the same time points, for group B, the concentrations were 8.66, 4.23, 3.22, and 1.65 µg/mL, respectively, and for group C, the concentrations were 4.81, 2.61, 2.52, and 1.75 µg/mL, respectively. The mean area under the curve (AUC)0-infinity for the free cisplatin concentration was 7.80 in group A, 2.48 in group B, and 2.27 in group C. The AUC0-infinity for the free cisplatin concentration gradually decreased, from group A to group C. Conclusions These results indicate that the combination of lipiodol and small GCs may be useful for delaying cisplatin drainage from the liver.
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Lin WY, Luo TY, Tsai SC, Kao CH, Tang IC, Huang PW. A comparison of Re-188-MN-16ET-lipiodol and transcatheter arterial chemoembolization in the treatment of hepatoma: An animal study. Nucl Med Biol 2013; 40:437-41. [DOI: 10.1016/j.nucmedbio.2012.11.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2012] [Revised: 10/31/2012] [Accepted: 11/19/2012] [Indexed: 01/13/2023]
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Imai N, Ikeda K, Seko Y, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H. Transcatheter arterial chemotherapy with miriplatin for hepatocellular carcinoma patients with chronic renal failure: report of three cases. Gut Liver 2013; 7:246-51. [PMID: 23560163 PMCID: PMC3607781 DOI: 10.5009/gnl.2013.7.2.246] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2011] [Revised: 04/29/2011] [Accepted: 06/12/2011] [Indexed: 12/11/2022] Open
Abstract
Miriplatin is a novel lipophilic platinum complex that was developed to treat hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting chronic renal failure, little prospective data are available regarding the clinical toxicity of chemotherapeutic agents used to treat HCC patients with chronic renal failure. In a phase II study, the plasma concentration of total platinum in patients who received miriplatin was very low, and no severe renal toxicity caused by miriplatin injection was reported. Here, we present three cases of HCC with stage 4 chronic renal failure who received transcatheter arterial chemotherapy with miriplatin. All cases were male, ages 72, 84, and 83 years, and had serum creatinine levels of 2.3, 1.6, and 1.9 mg/dL, respectively. Their estimated glomerular filtration rates were 21.9, 20.3, and 22.2 mL/min, respectively. All cases were treated for unresectable HCC with transcatheter arterial chemotherapy with miriplatin. No serious adverse events were observed, and serum creatinine levels did not elevate, even in the patient who experienced renal failure caused by cisplatin administration. These results might suggest that transcatheter arterial chemotherapy with miriplatin can be safely used in HCC patients with chronic renal failure.
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Affiliation(s)
- Norihiro Imai
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Yuya Seko
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | | | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | | | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | | | | | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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Shi M, Lu LG, Fang WQ, Guo RP, Chen MS, Li Y, Luo J, Xu L, Zou RH, Lin XJ, Zhang YQ. Roles played by chemolipiodolization and embolization in chemoembolization for hepatocellular carcinoma: single-blind, randomized trial. J Natl Cancer Inst 2012; 105:59-68. [PMID: 23150720 DOI: 10.1093/jnci/djs464] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The aim of our study was to compare the efficacy and safety of: 1) transarterial chemolipiodolization with gelatin sponge embolization vs chemolipiodolization without embolization, and 2) chemolipiodolization with triple chemotherapeutic agents vs epirubicin alone. METHODS A single-blind, three parallel arm, randomized trial was conducted at three clinical centers with patients with biopsy-confirmed unresectable hepatocellular carcinoma. Arm 1 received triple-drug chemolipiodolization and sponge embolization, whereas Arm 2 received triple-drug chemolipiodolization only. Patients in arm 3 were treated with single-drug chemolipiodolization and sponge embolization. We compared overall survival and time to progression. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS From July 2007 to November 2009, 365 patients (Arm 1: n = 122; Arm 2: n = 121; Arm 3: n = 122) were recruited. The median tumor size was 10.9cm (range = 7-22cm), and 34.5% had macrovascular invasion. The median survivals and time to progression in Arm 1, Arm 2, and Arm 3 were 10.5 and 3.6 months, 10.1 and 3.1 months, and 5.9 and 3.1 months, respectively. Survival was statistically significantly better in Arm 1 than in Arm 3 (P < .001), whereas there was no statistically significant difference between Arm 1 and Arm 2 (P = .20). Objective response rates were 45.9%, 29.7%, and 18.9% for Arm 1, Arm 2, and Arm 3, respectively. CONCLUSIONS Chemolipiodolization played an important role in transarterial chemoembolization, and the choice of chemotherapy regimen may largely affect survival outcomes. However, the removal of embolization from chemoembolization might not statistically significantly decrease survival.
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Affiliation(s)
- Ming Shi
- Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
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Short-term therapeutic effects of transcatheter arterial chemoembolization using miriplatin–lipiodol suspension for hepatocellular carcinoma. Jpn J Radiol 2012; 30:735-42. [DOI: 10.1007/s11604-012-0116-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2012] [Accepted: 08/06/2012] [Indexed: 01/13/2023]
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Zhou LH, Peng JH, Qian K, Qian J. Combined use of mitomycin, lipiodol and hepatic artery ligation for treating liver cancer in rats. Shijie Huaren Xiaohua Zazhi 2012; 20:1542-1546. [DOI: 10.11569/wcjd.v20.i17.1542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [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 establish a rat model of Walker 256 liver cancer to evaluate the role of embolic agents, lipiodol (LP) and chemotherapeutic agents in transcatheter arterial chemoembolization.
METHODS: Subcapsular implantation of carcinoma tissue of Walker 256 in the liver was carried out in 35 male SD rats. Tumor volume (V1) was measured by magnetic resonance imaging (MRI) on day 9 after implantation. All rats were randomly divided into experiment groups and control group by the agents which were injectd via the gastroduodenal artery to hepatic artery. The experiment groups included group A (n = 7), mitomycin (MMC, 0.1 mg) + LP (0.1 mL) + hepatic artery ligation (HAL); group B (n = 7), MMC (0.1 mg) + LP (0.1 mL); group C (n = 7), MMC (0.1 mg) + HAL; group D (n = 7), LP (0.1 mL) + HAL. The control group (group E, n = 7) was given 0.9% NaCl (0.1 mL). Tumor volume (V2) was assessed by MRI (on day 9 after treatment) and the growth ratio of tumor (V2/V1) was calculated.
RESULTS: The mean tumor volume before and after treatment was 0.017 cm3 ± 0.008 cm3, 0.038 cm3 ± 0.017 cm3; 0.019 cm3 ± 0.011 cm3, 0.152 cm3 ± 0.069 cm3; 0.022 cm3 ± 0.010 cm3, 0.302 cm3 ± 0.134 cm3; 0.019 cm3 ± 0.008 cm3, 0.382 cm3 ± 0.049 cm3; and 0.021 cm3 ± 0.006 cm3, 0.715 cm3 ± 0.307 cm3 in groups A, B, C, D and E, respectively. The tumor growth ratio (V2/V1) was 2.50 ± 1.08, 8.73 ± 2.38, 14.66 ± 4.96, 21.26 ± 5.19, 33.10 ± 8.17 in groups A, B, C, D and group E, respectively. The tumor growth ratio was significantly lower in the experiment groups than in the control group (all P < 0.05). There were significant differences in the tumor growth ratio among groups A, B, C and D (all P < 0.05).
CONCLUSION: Combined use of mitomycin, lipiodol and hepatic artery ligation could achieve satisfactory results in the treatment of liver cancer.
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Effect of transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma. J Gastroenterol 2012; 47:715-22. [PMID: 22322658 DOI: 10.1007/s00535-012-0537-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2011] [Accepted: 12/26/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND Transcatheter arterial infusion chemotherapy (TAI) using a combination of iodized oil (lipiodol) and degradable starch microspheres (DSMs) has been reported to be superior to TAI with either lipiodol or DSMs separately for the treatment of hepatocellular carcinoma (HCC), based on the results of a prospective randomized study. In the study reported here, we investigated the predictors influencing response and survival in HCC patients receiving TAI using lipiodol and DSMs. METHODS A total of 50 HCC patients [Child-Pugh A/B, 34/16 patients; maximum tumor size 2.9 cm (mean); tumor number <5/≥5 = 29/21 patients] were administered a mixture of cisplatin and lipiodol, followed by the injection of DSMs. RESULTS According to the criteria of the Liver Cancer Study Group of Japan, the response [complete response (CR) + partial response (PR)] rate and CR rate were 72 and 38%, respectively [CR, 19 patients; PR, 17; stable disease, 9; progressive disease, 5]. The 1-, 2-, 3-, and 4-year cumulative survival rates were 85, 67, 41, and 35%, respectively, and the median survival time was 32.6 months. Multivariate analysis identified tumor number <5 nodules [odds ratio 10.651, 95% confidence interval (CI) 2.168-52.317; P = 0.004] as an independent predictor of response and des-γ-carboxyprothrombin level <100 mAU/mL [hazard ratio (HR), 0.268, 95% CI 0.091-0.786, P = 0.017] and therapeutic effect CR or PR (HR 0.255, 95% CI 0.099-0.659; P = 0.005) as independent predictors of survival. CONCLUSION Transcatheter arterial infusion chemotherapy using lipiodol and DSMs might be considered as a potential intervention in HCC patients, especially those with tumors of <5 nodules.
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A transcatheter arterial chemotherapy using a novel lipophilic platinum derivative (miriplatin) for patients with small and multiple hepatocellular carcinomas. Eur J Gastroenterol Hepatol 2012; 24:583-8. [PMID: 22330234 DOI: 10.1097/meg.0b013e3283513488] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND/PURPOSE Miriplatin is a platinum complex developed to treat hepatocellular carcinoma (HCC) through administration into the hepatic artery as a sustained-release formulation suspended in lipiodol. A single-institute pilot study was conducted to investigate the antitumor efficacy of miriplatin infusion therapy for small and multiple HCCs. MATERIALS AND METHODS Small HCCs sized 2 cm or less, judged to be inadequate for curative treatment, were indicated for transcatheter arterial miriplatin infusion therapy. We prospectively investigated the course of patients treated with miriplatin between March 2010 and September 2010. Efficacy was evaluated by computed tomography at 4-8 weeks and the overall evaluation was carried out more than 3 months after treatment. RESULTS The study included 14 patients, of whom 13 were evaluable for efficacy. Of the 13 patients, one (8%) showed a complete response and three (23%) showed a partial response, with an overall response rate of 31%. Grade 3/4 hematological toxicity including thrombocytopenia was not seen. Increases to grade 3/4 in aspartate aminotransferase and alanine aminotransferase were observed for nonhematological toxicity. Irreversible deleterious changes in hepatic function were not seen. CONCLUSION Miriplatin infusion therapy showed safe and moderate effects on small HCCs. However, transarterial chemoembolization as a standard therapy cannot be replaced. We await the results of an ongoing study of transarterial chemoembolization with miriplatin.
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Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in Japan. Cancers (Basel) 2012; 4:165-83. [PMID: 24213234 PMCID: PMC3712670 DOI: 10.3390/cancers4010165] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Revised: 02/08/2012] [Accepted: 02/16/2012] [Indexed: 12/17/2022] Open
Abstract
Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.
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Imai Y, Chikayama T, Nakazawa M, Watanabe K, Ando S, Mizuno Y, Yoshino K, Sugawara K, Hamaoka K, Fujimori K, Inao M, Nakayama N, Oka M, Nagoshi S, Mochida S. Usefulness of miriplatin as an anticancer agent for transcatheter arterial chemoembolization in patients with unresectable hepatocellular carcinoma. J Gastroenterol 2012; 47:179-86. [PMID: 21976133 DOI: 10.1007/s00535-011-0475-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2011] [Accepted: 08/10/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND Injection of a suspension of miriplatin into the hepatic artery has been employed for the treatment of hepatocellular carcinoma (HCC). The efficacy and safety of transcatheter arterial chemoembolization (TACE) using miriplatin were evaluated. METHODS A total of 236 patients with unresectable HCC received miriplatin administration through the hepatic artery, followed by embolization with porous gelatin particles. The efficacy of this treatment modality was evaluated by contrast-enhanced computed tomography performed 1 month later and its safety based on the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS Miriplatin was used at a median dose of 66 mg. The therapeutic efficacy was evaluated in 130 patients, and the overall and complete response rates were 70.0 and 37.7%, respectively. The efficacies differed depending on the staging and Japan integrated staging (JIS) scores of the HCCs, with the overall and complete response rates being 87.7 and 66.7% for stage I and stage II HCC, and 56.2 and 15.1% for stage III and stage IV HCC, respectively; the corresponding rates were 93.2 and 70.5%, respectively, for HCCs with score 0 and score 1, and 58.1 and 20.9%, respectively, for those with scores 2-4. The stage of HCC was a significant independent factor associated with curative effects of TACE using miriplatin. Grade 3 elevation of serum transaminase levels was found in 23.4% of the patients; however, the values returned to the baseline levels. CONCLUSIONS Miriplatin is a useful and safe agent for TACE in patients with HCC stage I or II and/or JIS score 0 or 1 only when radiofrequency ablation and liver resection cannot be performed.
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Affiliation(s)
- Yukinori Imai
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan.
| | - Taku Chikayama
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Manabu Nakazawa
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Kazuhiro Watanabe
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Satsuki Ando
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Yoshie Mizuno
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Kiyoko Yoshino
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Kayoko Sugawara
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Kazuhiro Hamaoka
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Kenji Fujimori
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Mie Inao
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Masashi Oka
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Sumiko Nagoshi
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
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Brown DB, Nikolic B, Covey AM, Nutting CW, Saad WEA, Salem R, Sofocleous CT, Sze DY. Quality improvement guidelines for transhepatic arterial chemoembolization, embolization, and chemotherapeutic infusion for hepatic malignancy. J Vasc Interv Radiol 2012; 23:287-94. [PMID: 22284821 DOI: 10.1016/j.jvir.2011.11.029] [Citation(s) in RCA: 140] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2011] [Revised: 11/22/2011] [Accepted: 11/23/2011] [Indexed: 12/17/2022] Open
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Imai N, Ikeda K, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H. Transcatheter arterial chemotherapy using miriplatin-lipiodol suspension with or without embolization for unresectable hepatocellular carcinoma. Jpn J Clin Oncol 2011; 42:175-82. [PMID: 22210921 DOI: 10.1093/jjco/hyr189] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE The purpose of this retrospective study was to compare the anti-tumor and adverse effects of transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy using miriplatin-lipiodol suspension in patients with unresectable hepatocellular carcinoma. METHODS From 2007 to 2010, 162 consecutive patients with unresectable hepatocellular carcinoma were treated using miriplatin. Of these, 122 patients were treated by transcatheter arterial chemoembolization and 40 were treated by transcatheter arterial infusion chemotherapy. There were no significant differences in baseline characteristics between the two groups, except for prothrombin activity. Assessments were performed 1-3 months after treatment. RESULTS Objective responses were achieved in 13 patients undergoing transcatheter arterial infusion chemotherapy and 70 patients undergoing transcatheter arterial chemoembolization (33 versus 57%, P = 0.003). By multivariate logistic regression analysis, objective response was significantly associated with (i) a Lens culinaris agglutinin-reactive fraction of α-fetoprotein ≤10% (P = 0.004; risk ratio = 3.09; 95% confidence interval = 1.42-6.70), (ii) no previous transcatheter arterial chemoembolization (P = 0.007; risk ratio = 4.41; 95% confidence interval = 1.49-13.07) and (iii) transcatheter arterial chemoembolization using gelatin sponge 1 mm particles (P = 0.021; risk ratio = 2.97; 95% confidence interval = 1.17-7.49). Fever, anorexia and elevated serum transaminase levels were observed in most patients after miriplatin administration; there were no significant differences in the number of adverse effects between the two groups. CONCLUSIONS These results suggest that the addition of embolizing agents to a treatment regimen using miriplatin-lipiodol suspension can be safely used for patients with unresectable hepatocellular carcinoma. Objective response was achieved in a significantly higher number of transcatheter arterial chemoembolization patients than transcatheter arterial infusion chemotherapy patients.
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Affiliation(s)
- Norihiro Imai
- Department of Hepatology, Toranomon Hospital, Toranomon, Minato-ku, Tokyo, Japan.
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Jin B, Wang D, Lewandowski RJ, Ryu RK, Sato KT, Larson AC, Salem R, Omary RA. Quantitative 4D transcatheter intraarterial perfusion MRI for standardizing angiographic chemoembolization endpoints. AJR Am J Roentgenol 2011; 197:1237-43. [PMID: 22021520 PMCID: PMC3202346 DOI: 10.2214/ajr.10.5821] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The purpose of this study was to test the hypothesis that subjective angiographic endpoints during transarterial chemoembolization (TACE) of hepatocellular carcinoma are consistent and correlate with objective intraprocedural reductions in tumor perfusion determined with quantitative 4D transcatheter intraarterial perfusion MRI. SUBJECTS AND METHODS In this prospective study, 18 consecutively registered patients underwent TACE in a combined MRI-interventional radiology suite. Three board-certified interventional radiologists independently graded the angiographic endpoint of each procedure using a previously described subjective angiographic chemoembolization endpoint scale. A consensus endpoint rating was established for each patient. Patients underwent quantitative 4D transcatheter intraarterial perfusion MRI immediately before and after TACE, and mean whole tumor perfusion was calculated from the images. Consistency of subjective angiographic endpoint ratings between observers was evaluated with the intraclass correlation coefficient. The relation between the endpoint ratings and intraprocedural transcatheter intraarterial perfusion MRI changes was evaluated with the Spearman rank correlation coefficient. RESULTS The subjective angiographic chemoembolization endpoint rating scale showed very good consistency among all observers (intraclass correlation coefficient, 0.80). The consensus endpoint rating correlated significantly with both absolute (r = 0.54, p = 0.022) and percentage (r = 0.85, p < 0.001) reduction in intraprocedural perfusion. CONCLUSION The subjective angiographic chemoembolization endpoint rating scale shows very good consistency between raters and significantly correlates with objectively measured intraprocedural perfusion reductions during TACE. These results support the use of the scale as a standardized alternative method in quantitative 4D transcatheter intraarterial perfusion MRI to classify patients on the basis of embolic endpoints of TACE.
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Affiliation(s)
- Brian Jin
- Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA
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Ishikawa T, Higuchi K, Kubota T, Seki K, Honma T, Yoshida T, Kamimura T. Prevention of intrahepatic distant recurrence by transcatheter arterial infusion chemotherapy with platinum agents for stage I/II hepatocellular carcinoma. Cancer 2011; 117:4018-4025. [PMID: 21365625 DOI: 10.1002/cncr.25989] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2010] [Revised: 12/27/2010] [Accepted: 12/28/2010] [Indexed: 12/15/2022]
Abstract
BACKGROUND The effectiveness of additional chemotherapy in preventing intrahepatic distant tumor recurrence of hepatocellular carcinoma (HCC) has not been fully established. The authors compared the efficacy of 2 platinum-based chemotherapeutic agents in combination with radical local treatment for preventing intrahepatic distant recurrence (IDR). METHODS Seventy-eight patients with stage I/II HCC aged 45 to 85 years underwent transcatheter arterial chemoembolization and/or radiofrequency ablation after they received hepatic arterial infusion (HAI) of platinum compounds. The HAI consisted of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin) in 25 patients and cis-diamminedichloroplatinum (II) (cisplatin) in 53 patients. Multivariate analysis was used to identify independent factors that were associated with IDR. RESULTS Cumulative IDR rates at 1 year, 2 years, and 3 years were 21.7%, 52.2% and 75.7%, respectively, in the carboplatin group and 8.1%, 22.7%, and 36.9%, respectively, in the cisplatin group. The cisplatin group had a significantly lower IDR rate compared with the carboplatin group. The selection of a platinum agent was 1 of the independent factors for IDR in a multivariate Cox proportional hazards model. CONCLUSIONS HAI chemotherapy with cisplatin before radical local treatment was effective in patients with HCC. The authors concluded that radical local treatment with concurrent HAI using cisplatin may contribute to a longer progression-free period, which could be predicted with intrahepatic imaging in patients with stage I/II HCC.
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Affiliation(s)
- Toru Ishikawa
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan.
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Imai N, Ikeda K, Seko Y, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H. Previous chemoembolization response after transcatheter arterial chemoembolization (TACE) can predict the anti-tumor effect of subsequent TACE with miriplatin in patients with recurrent hepatocellular carcinoma. Oncology 2011; 80:188-94. [PMID: 21709428 DOI: 10.1159/000328749] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Accepted: 04/04/2011] [Indexed: 01/13/2023]
Abstract
AIM The purpose of this retrospective study was to evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) with miriplatin in patients with unresectable hepatocellular carcinoma (HCC). METHODS From 2007 to 2010, 122 consecutive patients with unresectable HCC were treated by TACE with miriplatin-lipiodol suspension in our institute. Twenty-two patients (18%) had a solitary nodule and 100 patients (82%) had multiple nodules. Ninety-eight patients (80%) had a history of TACE. RESULTS Thirty-five of the 122 treated patients (29%) showed complete response (CR). And no serious complications were observed. Patients who had shown CR after previous TACE (pre-CR) were significantly more likely to show CR in the current study compared with patients who had shown less successful responses after previous TACE (56 vs. 20%, p = 0.003). Multivariate analysis revealed that response after previous TACE (pre-CR, risk ratio: 4.76; p = 0.035), tumor multiplicity (solitary, risk ratio: 9.69; p = 0.003), and injection artery (peripheral to segmental hepatic artery, risk ratio: 5.28;p = 0.040) were significant independent predictors associated with CR after TACE using miriplatin. CONCLUSION In repetition of TACE treatment, switching the TACE agent from epirubicin or cisplatin to miriplatin offered a favorable treatment effect, especially in patients who had shown a CR after previous TACE.
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Affiliation(s)
- Norihiro Imai
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan. norihiro.imai @ gmail.com
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Chemoembolization endpoints: effect on survival among patients with hepatocellular carcinoma. AJR Am J Roentgenol 2011; 196:919-28. [PMID: 21427346 DOI: 10.2214/ajr.10.4770] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The purpose of this study was to investigate the relation between angiographic embolic endpoints of transarterial chemoembolization (TACE) and the survival of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study was a retrospective assessment of the cases of 105 patients with surgically unresectable HCC who underwent TACE. The cases were classified according to a previously established subjective angiographic chemoembolization endpoint scale. Only one patient had endpoint level I embolization and was excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was used to determine independent prognostic risk factors of survival. RESULTS The overall median survival period was 21.1 months (95% CI, 15.9-26.4 months). Patients with embolization to subjective angiographic chemoembolization endpoint levels II and III were aggregated and had a significantly longer median survival period (25.6 months; 95% CI, 16.2-35.0 months) than patients with embolization to level IV (17.1 months; 95% CI, 13.3-20.9 months) (p = 0.035). The results of multivariate analysis indicated that all of the following factors were independent negative prognostic indicators of survival: subjective angiographic chemoembolization endpoint level IV (hazard ratio [HR], 2.49; 95% CI, 1.41-4.42; p = 0.002), European Cooperative Oncology Group performance status greater than 0 (HR, 1.97; 95% CI, 1.15-3.37; p = 0.013), American Joint Committee on Cancer stage III or IV (HR, 2.42; 95% CI, 1.27-4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09-3.46; p = 0.025). CONCLUSION Embolization to an intermediate, substasis endpoint (subjective angiographic chemoembolization endpoint levels II and III) during TACE improves survival compared with embolization to a higher, stasis endpoint (level IV). Interventional oncologists should consider aiming for these intermediate, substasis angiographic endpoints during TACE.
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A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial. J Gastroenterol 2011; 46:359-66. [PMID: 20737175 DOI: 10.1007/s00535-010-0306-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2010] [Accepted: 08/02/2010] [Indexed: 02/04/2023]
Abstract
BACKGROUND We designed a novel transcatheter arterial infusion chemotherapy (TAI) using iodized oil (lipiodol) and degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) patients. In this study, we investigated the efficacy of TAI using lipiodol and DSM in a prospective randomized trial. METHODS We randomly divided 45 patients with HCC into 3 groups: TAI using lipiodol (lipiodol group, n = 15), TAI using DSM (DSM group, n = 15), and TAI using lipiodol and DSM (lipiodol + DSM group, n = 15). In the lipiodol group, a mixture of cisplatin and lipiodol was administered. In the DSM group, a mixture of cisplatin and DSM was administered. In the lipiodol + DSM group, a mixture of cisplatin and lipiodol was administered, followed by DSM. RESULTS The response rates were 40% in the lipiodol group, 53.4% in the DSM group, and 80% in the lipiodol + DSM group, respectively. The response rate tended to improve in the lipiodol + DSM group (lipiodol group vs. lipiodol + DSM group, P = 0.07). The median progression-free survival time was 177 days in the lipiodol group, 287 days in the DSM group, and 377 days in the lipiodol + DSM group. The progression-free survival in the lipiodol + DSM group was significantly better than those in the DSM group (P = 0.020) and the lipiodol group (P = 0.035). There were no serious adverse effects among the 3 groups. CONCLUSIONS TAI using lipiodol and DSM was superior to TAI using lipiodol only and TAI using DSM only because of improvements in therapeutic effects and progression-free survival.
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Kawaoka T, Aikata H, Takaki S, Hashimoto Y, Katamura Y, Hiramatsu A, Waki K, Takahashi S, Kamada K, Kitamoto M, Nakanishi T, Ishikawa M, Hieda M, Kakizawa H, Tanaka J, Chayama K. Transcatheter chemoembolization for unresectable hepatocellular carcinoma and comparison of five staging systems. Hepatol Res 2010; 40:1082-91. [PMID: 20880059 DOI: 10.1111/j.1872-034x.2010.00714.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
AIM We compared the ability of five staging system to predict survival in patients with hepatocellular carcinoma (HCC) treated with chemoembolization. METHODS The study subjects were 214 patients with HCC treated with repeated chemoembolization alone using cisplatin and lipiodol. Predictors of survival were assessed by multivariate analysis. Before chemoembolization was carried out, the modified Japan Integrated Staging (m-JIS), Japan Integrated Staging (JIS score), Barcelona (BCLC) stage, Liver Cancer Study Group of Japan/Tumor-Node-Metastasis (LCSGJ/TNM) and Italian score (CLIP score) were checked. To validate the prognostic value of these staging systems, the survival curve was obtained and analyzed by the Kaplan-Meier method. Discriminatory ability and predictive power were compared using Akaike's information criterion (AIC) score and the likelihood ratio (LR) χ(2) . RESULTS Overall survival was 1 year in 82.9%, 3 years in 39.9% and 5 years in 15.1%. Multivariate analysis identified more than 90% lipiodol accumulation (grade I) after the first chemoembolization (P = 0.001), absence of portal vein tumor thrombosis (PVTT) (P < 0.001) and liver damage A (P = 0.012) as independent determinants of survival. AIC score and the LR χ(2) showed superior predictive power of the m-JIS system in 95 patients with grade I accumulation of lipiodol after first chemoembolization. CONCLUSION The discriminate ability of the m-JIS score is substantially better than those of other staging systems and has better prognostic predictive power in patients with grade I accumulation of lipiodol after first chemoembolization.
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Affiliation(s)
- Tomokazu Kawaoka
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
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Ikeda M, Maeda S, Ashihara H, Nagahama H, Tanaka M, Sasaki Y. Transcatheter arterial infusion chemotherapy with cisplatin-lipiodol suspension in patients with hepatocellular carcinoma. J Gastroenterol 2010; 45:60-7. [PMID: 19655081 DOI: 10.1007/s00535-009-0109-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2008] [Accepted: 07/12/2009] [Indexed: 02/04/2023]
Abstract
PURPOSE The aim of this study was to investigate the antitumor efficacy of treatment, identify prognostic factors, and construct a prognostic index in patients with hepatocellular carcinoma treated by transcatheter arterial infusion chemotherapy (TAI) using cisplatin suspended in lipiodol. METHODS We analyzed the outcomes in a total of 94 consecutive patients with previously untreated hepatocellular carcinoma who were treated by TAI using cisplatin suspended in lipiodol. RESULTS Twenty-seven patients (29%) showed complete response and 21 patients (22%) showed partial response, with an overall response rate of 51% (95% confidence interval, 41-61%). The median survival time was 2.5 years and the proportions of survivors at 1, 2, and 5 years were 81.6, 65.2, and 18.3%, respectively. The results of multivariate analysis indicated a significant association of serum albumin > or =3.0 g/dL, maximum tumor size < or =3.0 cm, absence of ascites, and unilateral distribution of the tumors with a favorable survival. For clinical application, we also propose a prognostic index based on a combination of these prognostic factors. Based on this index, the patients were classified into three groups: those with good, intermediate, and poor prognosis. The median survival times in these three groups were 4.3, 2.7, and 1.1 years, respectively (p < 0.01). CONCLUSIONS TAI with cisplatin suspended in lipiodol exhibited favorable tumor efficacy and survival in patients with hepatocellular carcinoma. The prognostic factors identified and the index proposed based on these factors may be useful for predicting life expectancy, determining treatment strategies, and designing future clinical trials.
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Affiliation(s)
- Masafumi Ikeda
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan
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Moriguchi M, Takayama T, Nakamura M, Aramaki O, Higaki T, Nakayama H, Ohkubo T, Fujii M. Phase I/II study of a fine-powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinoma. Hepatol Res 2010; 40:369-75. [PMID: 20070392 DOI: 10.1111/j.1872-034x.2009.00606.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM The clinical feasibility of transcatheter arterial chemoembolization (TACE) with fine-powder cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC) has not been investigated. A phase I/II study was conducted to investigate the safety and tolerability of fine-powder CDDP when it was used with lipiodol and gelatin sponge particles for TACE. METHODS Fine-powder CDDP emulsified in lipiodol was injected into tumor arteries. Embolization was subsequently performed with gelatin sponge particles. The CDDP dose was started at 45 mg/m(2) (level 1) and increased to 65 mg/m(2) in 10 mg/m(2) increments. RESULTS Thirteen patients were enrolled in phase I study since no dose limiting toxicity was observed in any patients, even in seven patients at level 3 (65 mg/m(2)), the recommended dose was 65 mg/m(2). The major adverse event was grade 3 thrombocytopenia, which occurred in 8% of patients. The incidence of hematological toxicities was 15% for leukocytopenia, 84% for thrombocytopenia, and 84% for anemia. Increased serum total bilirubin was observed in 54% and increased aspartate aminotransferase or alanine aminotransferase in all patients. All digestive tract symptoms (nausea 77%, anorexia 84%, vomiting 31%) were grade 2 or lower. Total adverse events were grade 3 or higher in 44%. The response rate in 19 patients who received the recommended dose was 21%. CONCLUSIONS TACE with a fine-powder formulation of CDDP at a dose of 65 mg/m(2) is well tolerated in patients with unresectable HCC.
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Affiliation(s)
- Masamichi Moriguchi
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
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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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Ishikawa T. Future perspectives on the treatment of hepatocellular carcinoma with cisplatin. World J Hepatol 2009; 1:8-16. [PMID: 21160960 PMCID: PMC2998955 DOI: 10.4254/wjh.v1.i1.8] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2009] [Revised: 09/09/2009] [Accepted: 09/16/2009] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the commonest primary liver malignancy. Its incidence is increasing worldwide. Surgery, including transplantation resection, is currently the most effective treatment for HCC. However, recurrence rates are high and long-term survival is poor. Conventional cytotoxic chemotherapy has not provided clinical benefit or prolonged survival for patients with advanced HCC. Cisplatin (CDDP) is a key drug for the standard regimens of various cancers in the respiratory, digestive and genitourinary organs. Recently, several encouraging results have been shown in using CDDP in the treatment of advanced HCC patients. This review examines current knowledge regarding the chemotherapeutic potential of CDDP.
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Affiliation(s)
- Toru Ishikawa
- Toru Ishikawa, Department of Gastroenterology and Hepatology, Saiseikai Niigata Second Hospital, Niigata 950-1104, Japan
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Brown DB, Cardella JF, Sacks D, Goldberg SN, Gervais DA, Rajan DK, Vedantham S, Miller DL, Brountzos EN, Grassi CJ, Towbin RB, Angle JF, Balter S, Clark TWI, Cole PE, Drescher P, Freeman NJ, Georgia JD, Haskal Z, Hovsepian DM, Kilnani NM, Kundu S, Malloy PC, Martin LG, McGraw JK, Meranze SG, Meyers PM, Millward SF, Murphy K, Neithamer CD, Omary RA, Patel NH, Roberts AC, Schwartzberg MS, Siskin GP, Smouse HR, Swan TL, Thorpe PE, Vesely TM, Wagner LK, Wiechmann BN, Bakal CW, Lewis CA, Nemcek AA, Rholl KS. Quality improvement guidelines for transhepatic arterial chemoembolization, embolization, and chemotherapeutic infusion for hepatic malignancy. J Vasc Interv Radiol 2009; 20:S219-S226, S226.e1-10. [PMID: 19560002 DOI: 10.1016/j.jvir.2009.04.033] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2005] [Accepted: 10/29/2005] [Indexed: 01/01/2023] Open
Affiliation(s)
- Daniel B Brown
- Mallinckrodt Institute of Radiology, Siteman Cancer Center, Washington University School of Medicine, 510 South Kingshighway Boulevard, Box 8131, St. Louis, MO 63110, USA.
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