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Chen YF, Lin ZY, Chen LT, Zhang Y, Du ZQ. Cystic artery embolism after transarterial chemoembolization for hepatocellular carcinoma: A case report and review of the literature. World J Gastrointest Oncol 2025; 17:99129. [PMID: 40092942 PMCID: PMC11866240 DOI: 10.4251/wjgo.v17.i3.99129] [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] [Received: 07/14/2024] [Revised: 11/22/2024] [Accepted: 12/19/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Acute cholecystitis due to unintended cystic artery embolism is an uncommon and mostly self-limiting complication after transarterial chemoembolization procedure for treatment of hepatocellular carcinoma. Usually, conservative management is sufficient for complete recovery of patients who develop this complication. If conservative treatment is ineffective, urgent surgical intervention may be required to prevent the progression of complications. CASE SUMMARY This article reports a rare and serious case of acute cholecystitis complicated by gallbladder necrosis and biliary peritonitis, which was initially treated conservatively but eventually necessitated emergency laparotomy. The patient initially presented with equivocal symptoms of fever and upper abdominal pain and distention, which worsened at the two weeks mark along with emergence of signs of peritonitis. This was managed by emergency laparotomy and cholecystostomy, allowing rapid symptom relief. The patient ultimately discharged and succumbed to advanced liver cancer 11 months after diagnosis. CONCLUSION After cholecystostomy, the patient showed symptom relief and was discharged, surviving 11 months post-stage IIIB liver cancer diagnosis.
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Affiliation(s)
- Yi-Fan Chen
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Zhen-Yi Lin
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
- Medical Student, 10 Medical Dr, Singapore 117597, Singapore
| | - Lin-Tao Chen
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
- Xizang Minzu University, Xianyang 712082, Shaanxi Province, China
| | - Yu Zhang
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
| | - Zhao-Qing Du
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
- National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University of Xi'an, Xi'an 710069, Shaanxi Province, China
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Abi-Jaoudeh N, Sadeghi B, Javan H, Na J, Beaton G, Tucci F, Ravula S, Imagawa DK. Drug-Eluting Embolic Loaded with Tyrosine Kinase Inhibitor Targeted Therapies for Transarterial Chemoembolization in a VX2 Model. Cancers (Basel) 2023; 15:3236. [PMID: 37370846 DOI: 10.3390/cancers15123236] [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: 04/26/2023] [Revised: 06/05/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
Drug-eluting embolic transarterial chemoembolization (DEE-TACE) improves the overall survival of hepatocellular carcinoma (HCC), but the agents used are not tailored to HCC. Our patented liposomal formulation enables the loading and elution of targeted therapies onto DEEs. This study aimed to establish the safety, feasibility, and pharmacokinetics of sorafenib or regorafenib DEE-TACE in a VX2 model. DEE-TACE was performed in VX2 hepatic tumors in a selective manner until stasis using liposomal sorafenib- or regorafenib-loaded DEEs. The animals were euthanized at 1, 24, and 72 h timepoints post embolization. Blood samples were taken for pharmacokinetics at 5 and 20 min and at 1, 24, and 72 h. Measurements of sorafenib or regorafenib were performed in all tissue samples on explanted hepatic tissue using the same mass spectrometry method. Histopathological examinations were carried out on tumor tissues and non-embolized hepatic specimens. DEE-TACE was performed on 23 rabbits. The plasma concentrations of sorafenib and regorafenib were statistically significantly several folds lower than the embolized liver at all examined timepoints. This study demonstrates the feasibility of loading sorafenib or regorafenib onto commercially available DEEs for use in TACE. The drugs eluted locally without release into systemic circulation.
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Affiliation(s)
- Nadine Abi-Jaoudeh
- Department of Radiological Sciences, University of California Irvine, Orange, CA 92697, USA
| | - Ben Sadeghi
- Department of Radiological Sciences, University of California Irvine, Orange, CA 92697, USA
| | - Hanna Javan
- Department of Radiological Sciences, University of California Irvine, Orange, CA 92697, USA
| | - Jim Na
- Cullgen, Inc., San Diego, CA 92130, USA
| | | | - Fabio Tucci
- Epigen Biosciences, San Diego, CA 92121, USA
| | | | - David K Imagawa
- Department of Surgery, University of California Irvine, Orange, CA 92697, USA
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Safety, Efficacy and Distribution of Doxorubicin Loaded Radiopaque Beads in Chemoembolization in Intermediate Stage Hepatocellular Carcinoma (HCC) with Correlation with Local Response. Cardiovasc Intervent Radiol 2023; 46:337-349. [PMID: 36653660 DOI: 10.1007/s00270-022-03346-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 12/14/2022] [Indexed: 01/20/2023]
Abstract
PURPOSE The primary objectives of this study were to evaluate safety, and efficacy of Transarterial Chemoembolization (TACE) using doxorubicin-loaded radiopaque microspheres (DC Bead LUMI™) for the treatment of early and intermediate stage Hepatocellular Carcinoma (HCC) not amenable for curative treatments. Distribution of the microspheres was correlated with results post embolization. MATERIALS AND METHODS This was a prospective, single arm, open label study. The primary outcome measures were distribution of the radiopaque microspheres as showed by computerized tomography (CT) and local response measured by modified Response Evaluation Criteria (mRECIST) after Magnetic Resonance Imaging (MRI). Secondary measures were Time to Progression (TTP) and Overall Survival (OS). RESULTS Fifty patients were enrolled over 36 months. Median age was 69.0 years; mean sum of target lesions diameters was 78.6 ± 36.8 mm. There were no Grade 4 or 5 adverse events (AEs). At 6 months Complete Response (CR) (18%), Partial Response (PR) (62%), Objective Response OR (80%) and Stable Disease (SD) (20%) were recorded. Before embolization, Diffusion Weighted Imaging (DWI) showed high signal (restricted diffusion). Post procedure, patients with dense deposition (< 5 mm distance of microsphere aggregations) showed 100% absence of enhancement and no restriction in 30.6%. Median TTP was 8.3 months. TTP for patients with CR was 13.3 months and 7.2 and 5.6 for PR and SD, respectively. At 6 and 36 months, survival was 94% and 34%, respectively. CONCLUSION DC Bead LUMI™ is well tolerated and effective in early and intermediate stage HCC with maximal necrosis obtained in dense deposition in the target.
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Guo J, Wang W, Zhang Y, Xu L, Kong J. Comparison of initial tumor responses to transarterial bland embolization and drug-eluting beads-transarterial chemoembolization in the management of hepatocellular carcinoma: a propensity-score matching analysis. J Gastrointest Oncol 2021; 12:1838-1850. [PMID: 34532132 DOI: 10.21037/jgo-21-370] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/26/2021] [Indexed: 11/06/2022] Open
Abstract
Background Transarterial bland embolization (TABE) is widely used to treat the spontaneous rupture of hepatocellular carcinoma (HCC), and can lead to ischemic necrosis of the tumor. In this study, we used the propensity-score matching (PSM) method to compare the initial responses of treatment-naïve HCC patients to TABE and drug-eluting beads-transarterial chemoembolization (DEB-TACE), and the safety of these treatments. Methods Patients with treatment-naïve HCC, who had been admitted to 2 medical centers from January 2016 to December 2020, were enrolled as the research subjects. The data of 26 patients treated with TABE for ruptured HCC and 52 patients treated with DEB-TACE for primary HCC were collected according to our inclusion and exclusion criteria, and a PSM analysis was conducted to assess the safety and effectiveness of these two interventional techniques 1 month postoperatively. Results In relation to ruptured HCC, TABE had a hemostatic success rate of 97.0%. Before PSM, the TABE group had a larger maximum tumor diameter (P<0.05), a higher proportion of multiple tumors (P<0.05), a higher proportion of Child-Pugh class B (P<0.05), and a higher proportion of Barcelona Clinic Liver Cancer (BCLC) stage B (P<0.05) than the DEB-TACE group. After PSM, the baseline characteristics of these two groups were well balanced, and there was no significant difference in patients' initial therapeutic responses and tumor recurrence rates (both P>0.05). The multivariate regression analysis showed that tumor size was an independent predictor of the objective response rate (ORR) [odds ratio (OR): 3.312; 95% CI: 0.152-5.944; P<0.05]. Tumor number and BCLC stage also affected ORR; however, ORR was not significantly correlated with the interventional technique (TABE vs. DEB-TACE; P>0.05). The incidences of post-embolization syndrome (PES) and 48-h hepatotoxicity were significantly lower in the TABE group than the DEB-TACE group (both P<0.05), but there was no significant difference in hepatotoxicity after 1 month (P>0.05). Conclusions TABE is highly effective at managing hemorrhage from ruptured HCC. The initial therapeutic response of HCC to TABE is similar to that to DEB-TACE; however, TABE is associated with lower hepatotoxicity and fewer adverse effects, which paves the way for subsequent treatments and systemic therapies.
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Affiliation(s)
- Jianxi Guo
- Department of Interventional Radiology, Shenzhen People's Hospital (Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, China
| | - Weidong Wang
- Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanfang Zhang
- Department of Interventional Radiology, Shenzhen People's Hospital (Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, China
| | - Linfeng Xu
- Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jian Kong
- Department of Interventional Radiology, Shenzhen People's Hospital (Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, China
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Balli HT, Aikimbaev K. Intra-arterial Chemotherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma. LIVER CANCER IN THE MIDDLE EAST 2021:171-187. [DOI: 10.1007/978-3-030-78737-0_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Biocompatibility of a New Kind of Polyvinyl Alcohol Embolic Microspheres: In Vitro and In Vivo Evaluation. Mol Biotechnol 2019; 61:610-621. [PMID: 31144113 DOI: 10.1007/s12033-019-00166-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The aim of this study is to investigate the biocompatibility of polyvinyl alcohol (PVA) embolic microspheres by in vivo and in vitro evaluations. Two specifications of PVA microspheres including colorless microspheres (1 g microspheres with 7 mL 0.9% sodium chloride (SC) per vial, size: 500-700 µm) and blue microspheres (2 g microspheres with 7 mL 0.9% SC per vial, size: 500-700 µm) were assessed for biocompatibility. The vitro cytotoxicity was evaluated in L929 cells by MTT assay. Acute systemic toxicity and 28-repeat dose intravenous subchronic toxicity were assessed in 20 ICR mice and 40 SD rates, respectively. Skin sensitization was conducted in 30 adult albino guinea pigs by maximization test, in addition, intracutaneous reaction test was performed in New Zealand white rabbits. Hemolysis ratio of PVA microspheres was evaluated with rabbit blood. Moreover, test for genotoxicity was assessed by bacterial reverse mutation test and mouse lymphoma mutagenesis assay. No cytotoxicity, hemolysis, or acute toxicity of PVA microspheres was found, and slight fluctuations of biochemical indexes were observed in test of 28-day repeat dose intravenous subchronic toxicity, while these changes remained within our historical permitted range. Maximization test and intracutaneous reactivity test disclosed no irritation to skin or tissues. According to bacterial reverse mutation test and mouse lymphoma mutagenesis assay, no genotoxicity of PVA microspheres was observed. PVA microspheres showed excellent biocompatibility both in vivo and in vitro, and they were promising embolic materials for drug-eluting beads transarterial chemoembolization (DEB-TACE) therapy.
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Change in Perfusion Angiography During Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Predicts Short-Term Outcomes. AJR Am J Roentgenol 2019; 213:746-754. [DOI: 10.2214/ajr.18.20499] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Wen P, Chen SD, Wang JR, Zeng YH. Comparison of Treatment Response and Survival Profiles Between Drug-Eluting Bead Transarterial Chemoembolization and Conventional Transarterial Chemoembolization in Chinese Hepatocellular Carcinoma Patients: A Prospective Cohort Study. Oncol Res 2019; 27:583-592. [PMID: 31053181 PMCID: PMC7848295 DOI: 10.3727/096504018x15368325811545] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
This study evaluated the difference in treatment response and survival profiles between drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) treatments in Chinese hepatocellular carcinoma (HCC) patients. A total of 120 HCC patients were consecutively enrolled in this prospective cohort study, which showed that DEB-TACE achieved higher complete response (CR) (30.8%) compared with cTACE (7.4%) with no difference in overall response rate (ORR) for patients treated with DEB-TACE and cTACE (80.8% vs. 73.5%). In addition, DEB-TACE was associated with a lower rate of progressive disease (PD) compared with cTACE (1.9% vs. 11.8%). With respect to survival, patients in the DEB-TACE group achieved median progression-free survival (PFS) of 15 months (95% CI 12-18 months), which was longer than the cTACE group [median PFS 11 months (95% CI 10-12 months)]. Median overall survival (OS) was also longer with DEB-TACE [25 months (95% CI 22-28 months)] when compared with cTACE [21 months (95% CI 18-24 months)]. Univariate and multivariate logistic regression analysis showed that DEB-TACE was an independent predictive factor for achieving CR. Univariate Cox's regression analysis revealed that DEB-TACE was a predictive factor for prolonged PFS and OS, while multivariate analysis demonstrated that DEB-TACE was not an independent factor for predicting PFS or OS. In conclusion, we found that DEB-TACE achieved higher treatment response and prolonged survival compared with cTACE in Chinese HCC patients.
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Affiliation(s)
- Ping Wen
- Division of Liver Disease, Hubei Provincial Hospital of TCM, Garden Hill School District, Wuhan, Hubei, P.R. China
| | - Sheng-Duo Chen
- Division of Liver Disease, Hubei Provincial Hospital of TCM, Garden Hill School District, Wuhan, Hubei, P.R. China
| | - Jia-Rui Wang
- Huazhong University of Science and Technology Press, Wuhan, Hubei, P.R. China
| | - Ying-He Zeng
- Division of Liver Disease, Hubei Provincial Hospital of TCM, Garden Hill School District, Wuhan, Hubei, P.R. China
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Melchiorre F, Patella F, Pescatori L, Pesapane F, Fumarola E, Biondetti P, Brambillasca P, Monaco C, Ierardi AM, Franceschelli G, Carrafiello G. DEB-TACE: a standard review. Future Oncol 2018; 14:2969-2984. [PMID: 29987957 DOI: 10.2217/fon-2018-0136] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Drug-eluting bead transarterial chemoembolization (DEB-TACE) is a relative new endovascular treatment based on the use of microspheres to release chemotherapeutic agents within a target lesion with controlled pharmacokinetics. This aspect justifies the immediate success of DEB-TACE, that nowadays represents one of the most used treatments for unresectable hepatocellular carcinoma. However, there is no consensus about the choice of the best embolotherapy technique. In this review, we describe the available microspheres and report the results of the main comparative studies, to clarify the role of DEB-TACE in the hepatocellular carcinoma management. We underline that there is no evidence about the superiority of DEB-TACE over conventional TACE in terms of efficacy, but there may be some benefits with respect to safety especially with the improvement of new technologies.
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Affiliation(s)
- Fabio Melchiorre
- Diagnostic & Interventional Radiology Service, Sant'Andrea Hospital, Vercelli, Italy
| | - Francesca Patella
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy
| | - Lorenzo Pescatori
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy
| | - Filippo Pesapane
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy
| | - Enrico Fumarola
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy
| | | | | | - Cristian Monaco
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy
| | - Anna Maria Ierardi
- Diagnostic & Interventional Radiology Service, San Paolo Hospital, Milan, Italy
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Weng L, Akurati S, Donelson RB, Rostamzadeh P, Golzarian J. In vitro evaluation of sunitinib loaded bioresorbable microspheres for potential application in arterial chemoembolization. Colloids Surf B Biointerfaces 2017; 159:705-711. [PMID: 28881297 DOI: 10.1016/j.colsurfb.2017.08.038] [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: 03/21/2017] [Revised: 07/24/2017] [Accepted: 08/22/2017] [Indexed: 11/26/2022]
Abstract
Drug-loadable bioresorbable microspheres (BRMS) are designed for treating hypervascular tumors through chemoembolization, thereby reducing systemic side effects via controllable local delivery. The present study investigated the degradation and loading capability of bioresorbable microspheres with an anti-angiogenic agent, sunitinib, and then evaluated the release profiles in different media (PBS, 10μg/mL and 4mg/mL lysozyme solutions), and tested catheter deliverability as well as potential antiangiogenic effects of the loaded microspheres. The dry weight of the BRMS showed a consistent decrease over the period of incubation in a 10μg/mL lysozyme solution with 61.3% mass remaining on day 21. Sunitinib was loaded efficiently onto the microspheres, with smaller sizes exhibiting a slightly faster loading and release rate. At 2h, the loading percentages were 99.28%, 97.95%, and 94.39% for 100-300, 300-500, and 500-700μm microspheres, respectively. At 8h, the percentage of drug released were 78.4±5.8%, 71.7±0.3%, and 67.0±2.9% for 100-300, 300-500, and 500-700μm microspheres under static medium conditions, respectively. Under replacing-medium conditions, the presence of 10μg/mL lysozyme slightly delayed the drug release while 4mg/mL lysozyme significantly facilitated the drug release from the microspheres as compared with PBS solution. Confocal imaging revealed an even distribution of sunitinib throughout the microspheres. Drug loaded microspheres were delivered through microcatheters smoothly without any clogging. Sunitinib retained its efficacy at reducing the viability of human endothelial cells after elution from the microspheres. Thus, these bioresorbable microspheres are promising for arterial chemoembolization.
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Affiliation(s)
- Lihui Weng
- Department of Radiology, University of Minnesota, Mayo B228, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
| | - Srilalitha Akurati
- Department of Radiology, University of Minnesota, Mayo B228, 420 Delaware Street SE, Minneapolis, MN 55455, USA
| | - Randy B Donelson
- Department of Radiology, University of Minnesota, Mayo B228, 420 Delaware Street SE, Minneapolis, MN 55455, USA
| | - Parinaz Rostamzadeh
- Department of Radiology, University of Minnesota, Mayo B228, 420 Delaware Street SE, Minneapolis, MN 55455, USA
| | - Jafar Golzarian
- Department of Radiology, University of Minnesota, Mayo B228, 420 Delaware Street SE, Minneapolis, MN 55455, USA
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Waziry R, Grebely J, Amin J, Alavi M, Hajarizadeh B, George J, Matthews GV, Law M, Dore GJ. Survival following hospitalization with hepatocellular carcinoma among people notified with hepatitis B or C virus in Australia (2000-2014). Hepatol Commun 2017; 1:736-747. [PMID: 29404490 PMCID: PMC5678911 DOI: 10.1002/hep4.1073] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 06/27/2017] [Accepted: 06/29/2017] [Indexed: 12/23/2022] Open
Abstract
We assessed trends in HCC survival in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in New South Wales, Australia. Data on HBV (n = 54,399) and HCV (n = 96,908) notifications (1993‐2012) were linked to a hospitalization database (July 2000‐June 2014), the New South Wales Cancer Registry, and the New South Wales Death Registry. A total of 725 (1.3%) first HBV‐hepatocellular carcinoma (HCC) and 1,309 (1.4%) first HCV‐HCC hospitalizations were included. Death occurred in 60.4% of HBV‐HCC and 69.6% of HCV‐HCC patients. Median survival following first HBV‐HCC hospitalization improved from 0.6 years (95% confidence interval [CI] 0.39‐1.28) in 2000‐2004 to 2.8 years (1.54‐5.54) in 2010‐2014. Median survival following first HCV‐HCC hospitalization was 0.8 years (0.45‐1.33) in 2000‐2004 and 0.9 (0.67‐1.18) in 2010‐2014. One‐year HBV‐HCC survival in 2010‐2014 compared to 2000‐2004 improved for those with (94% versus 81%) and without (42% versus 33%) potentially curative procedures (liver resection, liver transplantation, and radiofrequency ablation). Factors associated with improved survival following HBV‐HCC were later study period (hazard ratio [HR] = 0.74; 95% CI, 0.57‐0.97) and potentially curative procedures (liver resection, liver transplantation, and radiofrequency ablation) (HR = 0.23; 95% CI, 0.17‐0.29), while male gender (HR = 1.37; 95% CI, 1.03‐1.82), human immunodeficiency virus coinfection (HR = 3.06; 95% CI, 1.36‐6.88), and Charlson Comorbidity Index ≥3 (HR = 1.81; 95% CI, 1.35‐2.40) were associated with reduced survival. Factors associated with improved survival following HCC‐HCV were Asia‐Pacific country of birth (HR = 0.68; 95% CI, 0.55‐0.84) and potentially curative procedures (HR = 0.21; 95% CI, 0.17‐0.25), while age (HR = 1.01; 95% CI, 1.01‐1.02), rural place of residence (HR = 1.46; 95% CI, 1.22‐1.74), and human immunodeficiency virus coinfection (HR = 2.71; 95% CI, 1.19‐6.15) were associated with reduced survival. Conclusion: All‐cause survival following HBV‐HCC has improved considerably, suggesting an impact of more effective antiviral therapy and earlier HCC diagnosis; in contrast, all‐cause survival for HCV‐HCC is unchanged. (Hepatology Communications 2017;1:736–747)
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Affiliation(s)
- Reem Waziry
- The Kirby Institute UNSW Sydney Sydney Australia
| | | | - Janaki Amin
- Faculty of Medicine and Health Sciences Macquarie University Sydney Australia
| | - Maryam Alavi
- The Kirby Institute UNSW Sydney Sydney Australia
| | | | - Jacob George
- Storr Liver Unit Westmead Millennium Institute and Westmead Hospital, University of Sydney Sydney Australia
| | | | - Matthew Law
- The Kirby Institute UNSW Sydney Sydney Australia
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Greco G, Cascella T, Facciorusso A, Nani R, Lanocita R, Morosi C, Vaiani M, Calareso G, Greco FG, Ragnanese A, Bongini MA, Marchianò AV, Mazzaferro V, Spreafico C. Transarterial chemoembolization using 40 µm drug eluting beads for hepatocellular carcinoma. World J Radiol 2017; 9:245-252. [PMID: 28634515 PMCID: PMC5441456 DOI: 10.4329/wjr.v9.i5.245] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Revised: 02/20/2017] [Accepted: 03/13/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment.
METHODS Drug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. Eleven out of the 48 treated patients treated progressed on to receive liver orthotopic transplantation (OLT). This allowed for histological analysis on the treated explanted nodules.
RESULTS DEB-TACE with 40 μm showed a good safety profile without major complications or 30-d mortality. The objective response rate of treated tumors was 72.6% and 26.7% according to mRECIST and RECIST respectively. Histological examination in 11 patients assigned to OLT showed a necrosis degree > 90% in 78.6% of cases. The overall time to progression was 13 mo (11-21).
CONCLUSION DEB-TACE with 40 μm particles is an effective treatment for the treatment of HCC in early-intermediate patients (Barcelona Clinic Liver Cancer stage A/B) with a good safety profile and good results in term of objective response rate and necrosis.
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Yu CY, Ou HY, Weng CC, Huang TL, Chen TY, Leung-Chit L, Hsu HW, Chen CL, Cheng YF. Drug-Eluting Bead Transarterial Chemoembolization as Bridge Therapy for Hepatocellular Carcinoma Before Living-Donor Liver Transplantation. Transplant Proc 2017; 48:1045-8. [PMID: 27320552 DOI: 10.1016/j.transproceed.2015.12.078] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Accepted: 12/30/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND The majority of hepatocellular carcinoma (HCC) patients is diagnosed in late stages and therefore becomes ineligible for potentially curative treatment such as resection or liver transplantation. Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads, Biocompatibles, Farnham, United Kingdom) has been proven with less side effects and better efficacy than conventional TACE, especially among patients with poor liver function. PURPOSE The aim of this study is to evaluate outcomes of HCC patients who received TACE with DC beads, which resulted to eligibility for liver transplantation. METHODS AND MATERIALS From January 2012 to June 2015, 60 patients with HCC received pre-liver transplantation evaluation whose cases were managed with TACE using DC beads at Kaohsiung Chang Gung Memorial Hospital were included in the study. DC beads loaded with doxorubicin were used. RESULTS Forty percent of the patients had complete tumor response. Thirty-three percent of the patients had partial tumor response, of which 15% showed stable disease, 11.7% exhibited disease progression including 3 with portal vein thrombosis, 1 with both hepatic vein and portal vein thrombosis, and 3 with increase in tumor size. Twenty-three patients were beyond University of California, San Francisco (UCSF) criteria initially. The successful downstage rate was 73.9% (17 of 23). Thirty-seven patients fit the USCF criteria initially. The 3-, 6- and 12-month drop rates of these patients were 0%, 3.9%, and 16.8%, respectively. Twenty-four (40%) patients successfully underwent liver transplantation. Three patients (12.5%) demonstrated recurrent HCC after liver transplantation. CONCLUSION TACE with DC bead can effectively induce tumor necrosis and appears to be a successful approach as bridge therapy for patients with advanced HCC and poor liver function.
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Affiliation(s)
- C-Y Yu
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - H-Y Ou
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - C-C Weng
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - T-L Huang
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - T-Y Chen
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - L Leung-Chit
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - H-W Hsu
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - C-L Chen
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Y-F Cheng
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Weng L, Tseng HJ, Rostamzadeh P, Golzarian J. In vitro comparative study of drug loading and delivery properties of bioresorbable microspheres and LC bead. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2016; 27:174. [PMID: 27752972 DOI: 10.1007/s10856-016-5786-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Accepted: 09/29/2016] [Indexed: 06/06/2023]
Abstract
Drug loadable bioresorbable microspheres (BRMS) are specially designed for the treatment of hypervascular tumors through arterial embolization. These microspheres consist of carboxymethyl chitosan crosslinked with carboxymethyl cellulose, and are available at different size ranges varying from 50 to 900 µm in diameter. Similar to commercially available non-resorbable drug eluting microspheres, LC Bead® microspheres (LCB), BRMS were capable of loading more than 99 % of doxorubicin, an anticancer drug, from the solution within 2 h with highly similar kinetics (difference factor f 1 = 0.36; similarity factor f 2 = 97.99). Doxorubicin loaded BRMS exhibited the highest elution rate in the 30 % ethanol aqueous solution saturated with potassium chloride, and the elution time depended on the ratio between the amount of loaded BRMS and the volume of elution media. After injection through microcatheters, BRMS have a higher recovery rate of the microsphere weight than LCB (90.96 vs. 79.63 %, P = 0.026). Although loaded BRMS eluted more drug into the injection medium than loaded LCB (8.63 vs. 3.80 %, P = 0.0015), there was no significant difference in the drug delivery rate between BRMS and LCB (83.88 vs. 86.65 %, P = 0.504). This study compares the loading capability as well as the drug delivery rate of BRMS and a commercial product under a condition simulating a transcatheter arterial chemoembolization procedure and demonstrates the potential of drug loaded BRMS for the treatment of hypervascular tumors such as hepatocellular carcinoma.
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Affiliation(s)
- Lihui Weng
- Department of Radiology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA
| | - Hsiang-Jer Tseng
- Department of Radiology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA
| | - Parinaz Rostamzadeh
- Department of Radiology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA
| | - Jafar Golzarian
- Department of Radiology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA.
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Nam HC, Jang B, Song MJ. Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma. World J Gastroenterol 2016; 22:8853-8861. [PMID: 27833376 PMCID: PMC5083790 DOI: 10.3748/wjg.v22.i40.8853] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Revised: 08/25/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023] Open
Abstract
Transarterial chemoembolization (TACE) is a widely used standard treatment for patients with hepatocellular carcinoma (HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia (conventional TACE). Recently, drug-eluting beads (DC Beads®) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads® can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads® substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drug-eluting beads for the treatment of HCC and discuss future therapeutic possibilities.
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Pharmacokinetics, Safety, and Efficacy of Chemoembolization with Doxorubicin-Loaded Tightly Calibrated Small Microspheres in Patients with Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 2016; 39:1379-91. [PMID: 27393274 DOI: 10.1007/s00270-016-1382-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Accepted: 05/19/2016] [Indexed: 02/08/2023]
Abstract
PURPOSE This study examines safety, efficacy, and pharmacokinetics of chemoembolization with loadable microspheres ≤100 μm for hepatocellular carcinoma. MATERIALS AND METHODS A pilot safety study was performed in 19 patients with size and dose escalation and then 52 patients were enrolled prospectively and randomly assigned to chemoembolization with TANDEM™ loaded with 150 or 100 mg of doxorubicin. RESULTS The mean diameter of the tumors was 7.28 ± 2.09 cm (range 4-12) and distribution dominant/multiple 51.9/48.1 %. Child A/B distribution was 32/20 (61.5/38.5 %) and etiology HBV/HCV/HBV/HCV-hemochromatosis was 61.6/9.6/9.6/15.4 %. Twenty-five patients were assigned in the low and 27 in the high loading group. There was 1.92 % thirty-day mortality due to lesion rupture. Biliary damage was seen in 3 patients (5.7 %) in the high loading. Mean maximum plasma concentration of doxorubicin C max ± SD was 284.9 ± 276.2 ng/mL for the high and 108.5 ± 77.6 ng/mL for the low loading (p < 0.001). According to m-RECIST overall objective response after two sessions reached 61.22 and 63.82 % at 6 months. Notably, complete target lesion response (CR) after the second session was observed in 28.57 % and maintained in 23.40 % at 6 months. No statistical differences in the local response rates were observed between the two loading groups. Overall survival (OS) at 6 months, 1 , 2, and 3 years was 98.08, 92.3, 88.46, and 82.6 %, respectively. OS and Progression-Free Survival did not demonstrate statistical significance between the two loading groups. CONCLUSION Initial evidence shows that (a) TANDEM™ achieves high rates of local response and mid-term survival, (b) high loading provides no clinical benefit and is associated with biliary toxicity.
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Baur J, Ritter CO, Germer CT, Klein I, Kickuth R, Steger U. Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma. Hepat Med 2016; 8:69-74. [PMID: 27382341 PMCID: PMC4920234 DOI: 10.2147/hmer.s105395] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Purpose In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE). Patients and methods In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever. Results No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1% vs 12.5%, P=0.0281). The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference. Conclusion No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE.
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Affiliation(s)
- Johannes Baur
- Department of General, Visceral, Vascular, and Pediatric Surgery
| | | | | | - Ingo Klein
- Department of General, Visceral, Vascular, and Pediatric Surgery
| | - Ralph Kickuth
- Institute of Radiology, University Hospital Würzburg, Würzburg, Germany
| | - Ulrich Steger
- Department of General, Visceral, Vascular, and Pediatric Surgery
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18
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Lewis AL, Dreher MR, O'Byrne V, Grey D, Caine M, Dunn A, Tang Y, Hall B, Fowers KD, Johnson CG, Sharma KV, Wood BJ. DC BeadM1™: towards an optimal transcatheter hepatic tumour therapy. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2016; 27:13. [PMID: 26676859 PMCID: PMC4681748 DOI: 10.1007/s10856-015-5629-6] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 11/12/2015] [Indexed: 05/04/2023]
Abstract
Clinical use of DC Bead™ loaded with doxorubicin (DEBDOX™) or irinotecan (DEBIRI™), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1 (TM), 70-150 μm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and drug dose delivered. Both unloaded and drug loaded DC BeadM1 were shown to have a greater density of distal volume of penetration although the ultimate distal level of penetration was the same as that of the 100-300 µm beads in an in vitro penetration model. Elution of doxorubicin was slower than irinotecan elution, but it was similar when comparing the same drug elution from 70 to 150 µm compared to 100-300 µm beads. Radiopaque versions of 70-150 and 100-300 µm beads were prepared in order to evaluate distribution ex vivo using µ-CT and doxorubicin distribution using epifluorescent microscopy. Liver distribution of the radiopaque versions of the beads was shown to be more distal and efficient at filling smaller vessels with the DC BeadM1 and correspondingly more beads were found per vessel histologically with a larger area of drug coverage with the smaller size range. This study indicates that the smaller (70-150 μm) beads should permit an increased dose of drug to be administered to both hypervascular and hypovascular tumours as compared to 100-300 µm beads.
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Affiliation(s)
- Andrew L Lewis
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK.
| | - Matthew R Dreher
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK
| | - Vincent O'Byrne
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK
| | - David Grey
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK
| | - Marcus Caine
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK
| | - Anthony Dunn
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK
| | - Yiqing Tang
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK
| | - Brenda Hall
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK
| | - Kirk D Fowers
- Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK
| | - Carmen Gacchina Johnson
- Center for Interventional Oncology, Department of Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Karun V Sharma
- Center for Interventional Oncology, Department of Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
- Children's National Medical Center, 1630 Euclid Street NW#1, Washington, DC, USA
| | - Bradford J Wood
- Center for Interventional Oncology, Department of Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
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Intra-arterial chemoembolization with hepasphere 50–100μm for patients with unresectable hepatocellular carcinoma: Initial experience in Egyptian Liver Hospital. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2015. [DOI: 10.1016/j.ejrnm.2015.05.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Chegai F, Orlacchio A, Merolla S, Monti S, Mannelli L. Intermediate hepatocellular carcinoma: the role of transarterial therapy. Hepat Oncol 2015; 2:399-408. [PMID: 26998220 PMCID: PMC4792112 DOI: 10.2217/hep.15.32] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
According to Barcelona Clinic Liver Cancer, the recommended first-line treatment for patients with intermediate stage of hepatocellular carcinoma (HCC) is transarterial chemoembolization. Patients with intermediate stage of HCC represent 20% with a 2-year survival of approximately 50%. Nowadays, transarterial therapies have proved precious in the treatment of hepatic malignancies. During the last years, there were important developments in practiced transarterial therapies and their efficacy is still controversial. The purpose of this review is to discuss in further details these transarterial therapies that have been used to treat cases of HCC.
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Affiliation(s)
- Fabrizio Chegai
- Department of Diagnostic & Molecular Imaging, Radiation Therapy & Interventional Radiology, University Hospital Tor Vergata, Rome, Italy
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C276, New York, NY 10065, USA
| | - Antonio Orlacchio
- Department of Diagnostic & Molecular Imaging, Radiation Therapy & Interventional Radiology, University Hospital Tor Vergata, Rome, Italy
| | - Stefano Merolla
- Department of Diagnostic & Molecular Imaging, Radiation Therapy & Interventional Radiology, University Hospital Tor Vergata, Rome, Italy
| | | | - Lorenzo Mannelli
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C276, New York, NY 10065, USA
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Hernández-Guerra M, Hernández-Camba A, Turnes J, Ramos LM, Arranz L, Mera J, Crespo J, Quintero E. Application of the Barcelona Clinic Liver Cancer therapeutic strategy and impact on survival. United European Gastroenterol J 2015; 3:284-93. [PMID: 26279838 DOI: 10.1177/2050640615575971] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Accepted: 01/26/2015] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND The Barcelona Clinic Liver Cancer (BCLC) classification of hepatocellular carcinoma (HCC) has proved useful in the management of HCC patients. However, BCLC-recommended first-line treatment is not always applicable in clinical practice. OBJECTIVE We performed a multicentre retrospective analysis of reasons for deviation from first-line treatment in 2008-2012. METHODS One to three-year survival data were analysed using Kaplan-Meier method. RESULTS A total of 407 consecutive HCC patients (66.6 ± 3 years, 83% male) with cirrhosis were included. Tumours were detected during surveillance in 53% of patients, grouped as Child-Pugh A (67%), B (25%) and C (8%); and BCLC A (including stage 0, 44%), B (26%), C (15%) and D (15%). In 31% of patients, first-line treatment was not feasible (51% in early stages) due to: technical reasons (74%); patient non-conformity (20%); medical decision (3%); and disease progression (3%). One to three-year survival of patients not receiving the recommended first-line treatment was similar to that of patients treated according to BCLC recommendations (log-rank, p = 0.229). CONCLUSION In real-life practice one-third of HCC patients could not receive first-line BCLC treatment. In our cohort of patients, similar short and medium-term survival was observed. Long-term prospective studies are required to determine the best alternative treatment option when BCLC first-line treatment is not feasible.
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Affiliation(s)
- Manuel Hernández-Guerra
- Gastroenterology and Hepatology Unit, Hospital Universitario de Canarias, La Laguna, Spain ; Institute of Biomedical Technologies and Center of Biomedical Research of the Canary Islands (CIBICAN), University of La Laguna, La Laguna, Spain ; Department of Medicine and Psychiatry, Universidad de La Laguna, La Laguna, Spain
| | | | - Juan Turnes
- Gastroenterology and Hepatology Unit, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - Luis Martin Ramos
- Gastroenterology and Hepatology Unit, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Laura Arranz
- Gastroenterology and Hepatology Unit, Hospital Universitario de Canarias, La Laguna, Spain
| | - José Mera
- Gastroenterology and Hepatology Unit, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - Javier Crespo
- Gastroenterology and Hepatology Unit, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Enrique Quintero
- Gastroenterology and Hepatology Unit, Hospital Universitario de Canarias, La Laguna, Spain ; Institute of Biomedical Technologies and Center of Biomedical Research of the Canary Islands (CIBICAN), University of La Laguna, La Laguna, Spain ; Department of Medicine and Psychiatry, Universidad de La Laguna, La Laguna, Spain
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Negussie AH, Dreher MR, Johnson CG, Tang Y, Lewis AL, Storm G, Sharma KV, Wood BJ. Synthesis and characterization of image-able polyvinyl alcohol microspheres for image-guided chemoembolization. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2015; 26:198. [PMID: 26105830 PMCID: PMC6663481 DOI: 10.1007/s10856-015-5530-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 06/10/2015] [Indexed: 05/15/2023]
Abstract
Therapeutic embolization of blood vessels is a minimally invasive, catheter-based procedure performed with solid or liquid emboli to treat bleeding, vascular malformations, and vascular tumors. Hepatocellular carcinoma (HCC) affects about half a million people per year. When unresectable, HCC is treated with embolization and local drug therapy by transarterial chemoembolization (TACE). For TACE, drug eluting beads (DC Bead(®)) may be used to occlude or reduce arterial blood supply and deliver chemotherapeutics locally to the tumor. Although this treatment has been shown to be safe and to improve patient survival, the procedure lacks imaging feedback regarding the location of embolic agent and drug coverage. To address this shortcoming, herein we report the synthesis and characterization of image-able drug eluting beads (iBeads) from the commercial DC Bead(®) product. Two different radiopaque beads were synthesized. In one approach, embolic beads were conjugated with 2,3,5-triiodobenzyl alcohol in the presence of 1,1'-carbonyldiimidazol to give iBead I. iBead II was synthesized with a similar approach but instead using a trimethylenediamine spacer and 2,3,5-triiodobenzoic acid. Doxorubicin was loaded into the iBeads II using a previously reported method. Size and shape of iBeads were evaluated using an upright microscope and their conspicuity assessed using a clinical CT and micro-CT. Bland and Dox-loaded iBeads II visualized with both clinical CT and microCT. Under microCT, individual bland and Dox loaded beads had a mean attenuation of 7904 ± 804 and 11,873.96 ± 706.12 HU, respectively. These iBeads have the potential to enhance image-guided TACE procedures by providing localization of embolic-particle and drug.
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Affiliation(s)
- Ayele H. Negussie
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20814
- Department of Targeted Therapeutics, MIRA Institute, University of Twente, The Netherlands
| | - Matthew R. Dreher
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20814
| | - Carmen Gacchina Johnson
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20814
| | - Yiqing Tang
- Bioccompatibles UK Ltd., Farnham Business Park, Weydon Lane, Farnham, Survey, GU98QL, UK
| | - Andrew L. Lewis
- Bioccompatibles UK Ltd., Farnham Business Park, Weydon Lane, Farnham, Survey, GU98QL, UK
| | - Gert Storm
- Department of Targeted Therapeutics, MIRA Institute, University of Twente, The Netherlands
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands
| | - Karun V. Sharma
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20814
| | - Bradford J. Wood
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20814
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Donati OF, Do RKG, Hötker AM, Katz SS, Zheng J, Moskowitz CS, Beattie C, Brown KT. Interreader and inter-test agreement in assessing treatment response following transarterial embolization for hepatocellular carcinoma. Eur Radiol 2015; 25:2779-88. [PMID: 25850892 DOI: 10.1007/s00330-015-3677-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 02/11/2015] [Accepted: 02/17/2015] [Indexed: 12/22/2022]
Abstract
PURPOSE To evaluate interreader and inter-test agreement in applying size- and necrosis-based response assessment criteria after transarterial embolization (TAE) for hepatocellular carcinoma (HCC), applying two different methods of European Association for the Study of the Liver (EASL) criteria. METHODS Seventy-four patients (median age, 67 years) from a prospectively accrued study population were included in this retrospective study. Four radiologists independently evaluated CT data at 2-3 (1st follow-up, FU) and 10-12 (2nd FU) weeks after TAE and assessed treatment response using size-based (WHO, RECIST) and necrosis-based (mRECIST, EASL) criteria. Enhancing tissue was bidimensionally measured (EASLmeas) and also visually estimated (EASLest). Interreader and inter-test agreements were assessed using intraclass correlation coefficient (ICC) and κ statistics. RESULTS Interreader agreement for all response assessment methods ranged from moderate to substantial (κ = 0.578-0.700) at 1st FU and was substantial (κ = 0.716-0.780) at 2nd FU. Inter-test agreement was substantial between WHO and RECIST (κ = 0.610-0.799, 1st FU; κ = 0.655-0.782, 2nd FU) and excellent between EASLmeas and EASLest (κ = 0.899-0.918, 1st FU; κ = 0.843-0.877, 2nd FU). CONCLUSION Size- and necrosis-based criteria both show moderate to excellent interreader agreement in evaluating treatment response after TAE for HCC. Inter-test agreement regarding EASLmeas and EASLest was excellent, suggesting that either may be used. KEY POINTS • Applying EASL criteria, visual estimation and bidimensional measurements show comparable interreader agreement. • EASL meas and EASL est show substantial interreader agreement for treatment response in HCC. • Agreement was excellent for EASL meas and EASL est after TAE of HCC. • Visual estimation of enhancement is adequate to assess treatment response of HCC.
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Affiliation(s)
- Olivio F Donati
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
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Toro A, Bertino G, Arcerito MC, Mannnino M, Ardiri A, Patane' D, Di Carlo I. A lethal complication after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. Case Rep Surg 2015; 2015:873601. [PMID: 25802793 PMCID: PMC4353438 DOI: 10.1155/2015/873601] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 02/02/2015] [Indexed: 12/16/2022] Open
Abstract
Background. The current standard of care for patients with large or multinodular noninvasive hepatocellular carcinoma is conventional transarterial chemoembolization (TACE). TACE may also be performed with drug-eluting beads, but serious complications of this procedure have been reported. Methods. Aim of this report is to present a patient affected by multifocal HCC who underwent TACE with drug-eluting bead (DEB-TACE). Results. Following the procedure the patient developed a hepatic abscess and biliobronchial fistula resulting in adult respiratory distress syndrome and death. Conclusion. We speculate that DEB-TACE has a prolonged effect on the tumor and the surrounding liver, resulting in progressive enlargement of the necrotic area. This activity that can extend to the surrounding healthy hepatic tissues may continue indefinitely.
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Affiliation(s)
- Adriana Toro
- Department of Surgical Sciences, Organ Transplantation and Advanced Technologies, University of Catania, Cannizzaro Hospital, 95100 Catania, Italy
| | - Gaetano Bertino
- Department of Internal Medicine and Systemic Disease, Hepatology Unit, University of Catania, S. Marta Hospital, 95100 Catania, Italy
| | | | - Maurizio Mannnino
- Department of Surgical Sciences, Organ Transplantation and Advanced Technologies, University of Catania, Cannizzaro Hospital, 95100 Catania, Italy
| | - Annalisa Ardiri
- Department of Internal Medicine and Systemic Disease, Hepatology Unit, University of Catania, S. Marta Hospital, 95100 Catania, Italy
| | - Domenico Patane'
- Department of Radiology, Cannizzaro Hospital, 95100 Catania, Italy
| | - Isidoro Di Carlo
- Department of Surgical Sciences, Organ Transplantation and Advanced Technologies, University of Catania, Cannizzaro Hospital, 95100 Catania, Italy
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Spreafico C, Cascella T, Facciorusso A, Sposito C, Rodolfo L, Morosi C, Civelli EM, Vaiani M, Bhoori S, Pellegrinelli A, Marchianò A, Mazzaferro V. Transarterial chemoembolization for hepatocellular carcinoma with a new generation of beads: clinical-radiological outcomes and safety profile. Cardiovasc Intervent Radiol 2015; 38:129-134. [PMID: 24870698 DOI: 10.1007/s00270-014-0907-0] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Accepted: 04/10/2014] [Indexed: 12/15/2022]
Abstract
PURPOSE To evaluate the short-term safety and efficacy of the new generation of 70-150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT). METHODS Forty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response. RESULTS All patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1-6) and 43 mm (range 10-190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2-4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures). CONCLUSION DEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.
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Affiliation(s)
- Carlo Spreafico
- Department of Radiology, Fondazione Istituto Tumori, via Venezian 1, 20133, Milan, Italy,
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Liu YS, Ou MC, Tsai YS, Lin XZ, Wang CK, Tsai HM, Chuang MT. Transarterial chemoembolization using gelatin sponges or microspheres plus lipiodol-doxorubicin versus doxorubicin-loaded beads for the treatment of hepatocellular carcinoma. Korean J Radiol 2015; 16:125-32. [PMID: 25598680 PMCID: PMC4296259 DOI: 10.3348/kjr.2015.16.1.125] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2014] [Accepted: 09/25/2014] [Indexed: 02/07/2023] Open
Abstract
Objective To retrospectively compare treatment of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) using gelatin sponges or microspheres plus lipiodol-doxorubicin vs. doxorubicin-loaded drug-eluting beads (DEB). Materials and Methods A total of 158 patients with HCC received TACE from November 2010 to November 2011 were enrolled in this study, including 64 (40.5%) received TACE with lipiodol-doxorubicin and gelatin sponges (group A), 41 (25.9%) received TACE with lipiodol-doxorubicin and microspheres (group B), and 53 (33.5%) received TACE with doxorubicin-loaded DEB (group C). Tumor response and adverse events (AEs) were evaluated. Results No significant difference was found at baseline among the three groups. The doxorubicin dosage in group C was significantly (p < 0.001) higher compared to the dose used in groups A or B (median, 50 mg vs. 31 mg or 25 mg). Significantly (p < 0.001) more patients in group C achieved complete response compared to those in groups A or B (32.1% vs. 6.3% or 2.4%). Significantly (p < 0.001) less patients in group C had progressive disease compared to those in groups A or B (34.0% vs. 57.8% or 68.3%). Minor AEs were more common in groups A and B compared to group C, with rates of 54.7%, 34.1%, and 5.7%, respectively. Conclusion In patients with HCC, TACE with DEB offers better safety and efficacy profiles compared to either TACE with gelatin sponges or TACE with microspheres.
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Affiliation(s)
- Yi-Sheng Liu
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C. ; Liver Cancer Collaborative Oncology Group, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Ming-Ching Ou
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Yi-Shan Tsai
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Xi-Zhang Lin
- Liver Cancer Collaborative Oncology Group, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C. ; Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Chien-Kuo Wang
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Hong-Ming Tsai
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C. ; Liver Cancer Collaborative Oncology Group, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Ming-Tsung Chuang
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
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Xie ZB, Wang XB, Peng YC, Zhu SL, Ma L, Xiang BD, Gong WF, Chen J, You XM, Jiang JH, Li LQ, Zhong JH. Systematic review comparing the safety and efficacy of conventional and drug-eluting bead transarterial chemoembolization for inoperable hepatocellular carcinoma. Hepatol Res 2015; 45:190-200. [PMID: 25388603 DOI: 10.1111/hepr.12450] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Revised: 10/28/2014] [Accepted: 11/05/2014] [Indexed: 02/06/2023]
Abstract
AIM Conventional transarterial chemoembolization (cTACE) is widely used for treating patients with inoperable hepatocellular carcinoma (HCC). A variation on the technique based on drug-eluting beads (DEB-TACE) has recently entered the clinic, but trials of its safety and efficacy have given conflicting results. This systematic review aimed to gain a current, comprehensive picture of how DEB-TACE compares with cTACE. METHODS MEDLINE, EMBASE, the Cochrane Library, the Chinese National Knowledge Infrastructure database and clinical trial registries were searched through June 2014. Risk ratios (RR), hazard ratios (HR) and 95% confidence intervals (CI) were calculated. RESULTS The analysis included four randomized controlled trials, one uncontrolled prospective study and one prospective case-control study, altogether involving 652 patients. Overall survival benefit was similar between cTACE and DEB-TACE patients (HR = 1.07, 95% CI = 0.82-1.40, P = 0.875). However, DEB-TACE was associated with a significantly higher objective tumor response rate (RR = 1.14, 95% CI = 1.01-1.29, P = 0.03) and a slightly lower incidence of adverse events. CONCLUSION Though the available evidence suggests that although DEB-TACE is associated with better tumor response and potentially fewer adverse events, it does not provide greater survival benefit than cTACE. These results need to be validated in high-quality trials with large sample size.
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Affiliation(s)
- Zhi-Bo Xie
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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De Minicis S, Marzioni M, Benedetti A, Svegliati-Baroni G. New insights in hepatocellular carcinoma: from bench to bedside. ANNALS OF TRANSLATIONAL MEDICINE 2014; 1:15. [PMID: 25332959 DOI: 10.3978/j.issn.2305-5839.2013.01.06] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Accepted: 01/31/2013] [Indexed: 01/10/2023]
Abstract
Hepatocarcinogenesis is a multistep process involving different genetic alterations that ultimately lead to malignant transformation of the hepatocyte. The liver is one of the main targets for different metastatic foci, but it represents an important and frequent locus of degeneration in the course of chronic disease. In fact, Hepatocellular carcinoma (HCC) represents the outcome of the natural history of chronic liver diseases, from the condition of fibrosis, to cirrhosis and finally to cancer. HCC is the sixth most common cancer in the world, some 630,000 new cases being diagnosed each year. Furthermore, about the 80% of people with HCC, have seen their clinical history developing from fibrosis, to cirrhosis and finally to cancer. The three main causes of HCC development are represented by HBV, HCV infection and alcoholism. Moreover, metabolic disease [starting from Non Alcoholic Fatty Liver Disease (NAFLD), Non Alcoholic Steatohepatitis (NASH)] and, with reduced frequency, some autoimmune disease may lead to HCC development. An additional rare cause of carcinogenetic degeneration of the liver, especially developed in African and Asian Countries, is represented by aflatoxin B1. The mechanisms by which these etiologic factors may induce HCC development involve a wide range of pathway and molecules, currently under investigation. In summary, the hepatocarcionogenesis results from a multifactorial process leading to the common condition of genetic changes in mature hepatocytes mainly characterized by uncontrolled proliferation and cell death. Advances in understanding the mechanism of action are fundamental for the development of new potential therapies and results primarily from the association of the research activities coming from basic and clinical science. This review article analyzes the current models used in basic research to investigate HCC activity, and the advances obtained from a basic and clinical point of view.
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Affiliation(s)
- Samuele De Minicis
- Department of Gastroenterology, Università Politecnica delle Marche, Ancona, Italy
| | - Marco Marzioni
- Department of Gastroenterology, Università Politecnica delle Marche, Ancona, Italy
| | - Antonio Benedetti
- Department of Gastroenterology, Università Politecnica delle Marche, Ancona, Italy
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Andersen KJ, Grønbaek H, Villadsen GE, Knudsen AR, Ott P, Vildstrup H, Nielsen DT, Bharadwaz A. Chemoembolization of intermediate stage hepatocellular carcinomas: results from a Nordic tertiary liver cancer center. Indian J Gastroenterol 2014; 33:322-9. [PMID: 24307495 DOI: 10.1007/s12664-013-0428-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Accepted: 10/14/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Transarterial chemoembolization (TACE) is used as palliative treatment of hepatocellular carcinoma (HCC). Most publications are from HCC patient populations where viral hepatitis is the primary cause of liver disease. In the Nordic countries, most patients have either alcohol-induced cirrhosis or are noncirrhotic. The aim of this single-center study was to evaluate patient characteristics, survival, and side effects of TACE in a Danish referral center for HCC treatment. METHODS Fifty-nine consecutive patients with HCC, treated with TACE, either chemoembolization with drug-eluting beads or conventional-TACE with Lipiodol, were included in the study. Their medical records were retrospectively reviewed, computed tomography images analyzed, and biochemical markers recorded. The primary endpoint was overall survival. Analyses were by intention to treat. RESULTS Thirty-five patients (59 %) had HCC on a background of liver cirrhosis most often caused by alcohol (60 % of cirrhotics or 35 % overall). Before the first chemoembolization, the patients had a median Child-Pugh score of 6 (5-7) and a median MELD score of 10 (6-21). Median survival after chemoembolization was 18.9 months (13.1-24.7). TACE patients were hospitalized for an average of 3 days (2-30). Prolonged stay was most often due to side effects-eg. pain (31 %), fever (14 %), nausea (10 %), and infection (10 %). Thirty-three patients (56 %) did not have any side effects. CONCLUSIONS In this cohort, we observed an acceptable survival following TACE without significant side effects.
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Affiliation(s)
- Kasper J Andersen
- Department of Surgical Gastroenterology (Dept. L), Aarhus University Hospital, Nørrebrogade 44, Aarhus C, 8000, Aarhus, Denmark,
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Molla N, AlMenieir N, Simoneau E, Aljiffry M, Valenti D, Metrakos P, Boucher LM, Hassanain M. The role of interventional radiology in the management of hepatocellular carcinoma. ACTA ACUST UNITED AC 2014; 21:e480-92. [PMID: 24940108 DOI: 10.3747/co.21.1829] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (hcc) is one of the most common causes of cancer-related death worldwide. Overall, liver transplantation and resection are the only available treatments with potential for cure. Various locoregional therapies are widely used to manage patients with advanced hcc or as a bridging therapy for patients with early and intermediate disease. This article reviews and evaluates the role of interventional radiology in the management of such cases by assessing various aspects of each method, such as effect on rates of survival, recurrence, tumour response, and complications. METHODS A systemic search of PubMed, medline, Ovid Medline In-Process, and the Cochrane Database of Systematic Reviews retrieved all related scientific papers for review. RESULTS Needle core biopsy is a highly sensitive, specific, and accurate method for hcc grading. Portal-vein embolization provides adequate expansion of the future liver remnant, making more patients eligible for resection. In focal or multifocal unresectable early-stage disease, radiofrequency ablation tops all other thermoablative methods. However, microwave ablation is preferred in large tumours and in patients with Child-Pugh B disease. Cryoablation is preferred in recurrent disease and in patients who are poor candidates for anesthesia. Of the various transarterial modalities-transarterial chemoembolization (tace), drug-eluting beads, and transarterial radio-embolization (tare)-tace is the method of choice in Child-Pugh A disease, and tare is the method of choice in hcc cases with portal vein thrombosis. CONCLUSIONS The existing data support the importance of a multidisciplinary approach in hcc management. Large randomized controlled studies are needed to provide clear indication guidelines for each method.
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Affiliation(s)
- N Molla
- Department of Radiology, King Saud University, Riyadh, Saudi Arabia. ; Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC
| | - N AlMenieir
- Department of Radiology, King Saud University, Riyadh, Saudi Arabia
| | - E Simoneau
- Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC
| | - M Aljiffry
- Department of Surgery, King Abdulaziz University, Jeddah, Saudi Arabia
| | - D Valenti
- Department of Radiology, McGill University Health Centre, Montreal, QC
| | - P Metrakos
- Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC. ; Department of Surgery, King Saud University, Riyadh, Saudi Arabia
| | - L M Boucher
- Department of Radiology, McGill University Health Centre, Montreal, QC
| | - M Hassanain
- Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC. ; Department of Surgery, King Saud University, Riyadh, Saudi Arabia
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Malagari K, Emmanouil E, Pomoni M, Kelekis D. Chemoembolization with DC Bead™ for the treatment of hepatocellular carcinoma: an update. Hepat Oncol 2014; 1:205-214. [PMID: 30190955 DOI: 10.2217/hep.13.18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
In this review, DC Bead™ for the treatment of hepatocellular carcinoma is discussed. The embolic device and its mechanism of action is described, focusing on the clinical application and the preclinical background. Guidelines for patient selection and management, along with technical considerations for the appropriate use are provided. Clinical details including local response, comparison with conventional chemoembolization and bland embolization, survival and safety issues are also discussed in detail.
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Affiliation(s)
- Katerina Malagari
- 2nd Department of Radiology University of Athens, Medical School, 19 Monis Kyccou, 15 669 Papagou, Athens, Greece
| | - Emmanouil Emmanouil
- 2nd Department of Radiology University of Athens, Medical School, 19 Monis Kyccou, 15 669 Papagou, Athens, Greece
| | - Maria Pomoni
- 2nd Department of Radiology University of Athens, Medical School, 19 Monis Kyccou, 15 669 Papagou, Athens, Greece
| | - Dimitrios Kelekis
- 2nd Department of Radiology University of Athens, Medical School, 19 Monis Kyccou, 15 669 Papagou, Athens, Greece
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Bester L, Meteling B, Boshell D, Chua TC, Morris DL. Transarterial chemoembolisation and radioembolisation for the treatment of primary liver cancer and secondary liver cancer: A review of the literature. J Med Imaging Radiat Oncol 2014; 58:341-52. [PMID: 24589204 DOI: 10.1111/1754-9485.12163] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 12/23/2013] [Indexed: 02/06/2023]
Affiliation(s)
- Lourens Bester
- Department of Interventional Radiology; St Vincent's Hospital; University of New South Wales; Sydney New South Wales Australia
| | - Baerbel Meteling
- Department of Interventional Radiology; St Vincent's Hospital; University of New South Wales; Sydney New South Wales Australia
| | - David Boshell
- Department of Interventional Radiology; St Vincent's Hospital; University of New South Wales; Sydney New South Wales Australia
| | - Terence C. Chua
- Department of Surgery; St George Hospital; University of New South Wales; Sydney New South Wales Australia
| | - David L. Morris
- Department of Surgery; St George Hospital; University of New South Wales; Sydney New South Wales Australia
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Jazieh KA, Arabi M, Khankan AA. Transarterial therapy: an evolving treatment modality of hepatocellular carcinoma. Saudi J Gastroenterol 2014; 20:333-41. [PMID: 25434313 PMCID: PMC4271007 DOI: 10.4103/1319-3767.145315] [Citation(s) in RCA: 4] [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] [Indexed: 01/06/2023] Open
Abstract
Liver cancer is the fifth most common cancer in men, the seventh most common in women, and the third most common cause of death from cancer worldwide. Only 30-40% of liver cancer patients present early enough to undergo curative treatments such as surgery or liver transplantation. Local treatment with radiofrequency ablation or ethanol injection is often reserved for non-surgical candidates with early stages of disease. Transarterial embolization has become a widely accepted treatment for asymptomatic patients with unresectable lesions. This review discusses in details the three major forms of transarterial therapies: Bland embolization, chemoembolization, and radioembolization.
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Affiliation(s)
- Khalid A. Jazieh
- College of Medicine, Alfaisal University, Riyadh, KSA,Address for correspondence: Mr. Khalid A. Jazieh, Alfaisal University, P.O. Box 50927, Riyadh 11533, Kingdom of Saudi Arabia. E-mail:
| | - Mohammad Arabi
- Department of Medical Imaging, Prince Sultan Military Medical City, Riyadh, KSA
| | - Azzam A. Khankan
- Department of Medical Imaging, King Abdulaziz Medical City, Riyadh, KSA
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SISTA AKHILESHK, MADOFF DAVIDC. Interventional management of hepatocellular carcinoma. CLINICAL INTERVENTIONAL ONCOLOGY 2014:76-87. [DOI: 10.1016/b978-1-4557-1221-2.00017-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Malagari K, Pomoni M, Moschouris H, Kelekis A, Charokopakis A, Bouma E, Spyridopoulos T, Chatziioannou A, Sotirchos V, Karampelas T, Tamvakopoulos C, Filippiadis D, Karagiannis E, Marinis A, Koskinas J, Kelekis DA. Chemoembolization of hepatocellular carcinoma with HepaSphere 30-60 μm. Safety and efficacy study. Cardiovasc Intervent Radiol 2013; 37:165-75. [PMID: 24263774 PMCID: PMC3895279 DOI: 10.1007/s00270-013-0777-x] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Accepted: 09/01/2013] [Indexed: 02/07/2023]
Abstract
Background This study examined the safety, pharmacokinetics, and efficacy of transarterial chemoembolization of hepatocellular carcinoma (HCC) using a newly developed size of a superabsorbent polymer drug-eluting embolic material. Methods Forty-five patients with documented HCC (Child–Pugh score A/B: 55.5 %/44.5 %) were embolized with HepaSphere microspheres 30–60 μm with escalation of lesion, dose, and frequency of re-embolization. Local response was evaluated with modified response evaluation criteria in solid tumors (mRECIST). Plasma levels of doxorubicin were measured in 24 patients at baseline and at 5, 20, 40, 60, and 120 min, at 6, 24, and 48 h, and at 7 days, respectively, to determine doxorubicin in plasma (Cmax) and area under the curve (AUC). Measurements of three patients who underwent lipiodol-based conventional chemoembolization (c-TACE) were also performed. Results TACE with HepaSphere was well tolerated with an acceptable safety profile and no 30-day mortality. Response rates were calculated on intention-to-treat basis with complete response (CR) in 17.8 % reaching 22.2 % for the target lesion. Overall partial response (PR) was seen in 51.1 %, stable disease in 20 %, and progressive disease in 11.1 % of patients. Overall objective response (CR + PR), including patients treated at all dosages of doxorubicin, was seen in 68.9 % of cases. After a median follow-up of 15.6 months, 1-year survival is 100 %. Doxorubicin AUC was significantly lower in patients with HepaSphere 30–60 μm (35,195 ± 27,873 ng × min/ml) than in patients with conventional TACE (103,960 ± 16,652 ng × min/ml; p = 0.009). Cmax was also significantly lower with HepaSphere 30–60 μm (83.9 ± 32.1 ng/ml) compared with c-TACE (761.3 ± 58.8 ng/ml; p = 0.002). Conclusion HepaSphere 30–60 μm is an effective drug-eluting embolic material with a favourable pharmacokinetic profile.
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Lilienberg E, Ebeling Barbier C, Nyman R, Hedeland M, Bondesson U, Axén N, Lennernäs H. Investigation of hepatobiliary disposition of doxorubicin following intrahepatic delivery of different dosage forms. Mol Pharm 2013; 11:131-44. [PMID: 24171458 DOI: 10.1021/mp4002574] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Unresectable, intermediate stage hepatocellular carcinoma (HCC) is often treated palliatively in humans by doxorubicin (DOX). The drug is administered either as a drug-emulsified-in-Lipiodol (DLIP) or as drug loaded into drug eluting beads (DEB), and both formulations are administered intrahepatically. However, several aspects of their in vivo performance in the liver are still not well-understood. In this study, DLIP and DEB were investigated regarding the local and systemic pharmacokinetics (PK) of DOX and its primary metabolite doxorubicinol (DOXol). An advanced PK-multisampling site acute in vivo pig model was used for simultaneous sampling in the portal, hepatic, and femoral veins and the bile duct. The study had a randomized, parallel design with four treatment groups (TI-TIV). TI (n = 4) was used as control and received an intravenous (i.v.) infusion of DOX as a solution. TII and TIII were given a local injection in the hepatic artery with DLIP (n = 4) or DEB (n = 4), respectively. TIV (n = 2) received local injections of DLIP in the hepatic artery and bile duct simultaneously. All samples were analyzed for concentrations of DOX and DOXol with UPLC-MS/MS. Compared to DLIP, the systemic exposure for DOX with DEB was reduced (p < 0.05), in agreement with a slower in vivo release. The approximated intracellular bioavailability of DOX during 6 h appeared to be lower for DEB than DLIP. Following i.v. infusion (55 min), DOX had a liver extraction of 41 (28-53)%, and the fraction of the dose eliminated in bile of DOX and DOXol was 20 (15-22)% and 4.2 (3.2-5.2)%, respectively. The AUCbile/AUCVP for DOX and DOXol was 640 (580-660) and 5000 (3900-5400), respectively. In conclusion, DLIP might initially deliver a higher hepatocellular concentration of DOX than DEB as a consequence of its higher in vivo release rate. Thus, DLIP delivery results in higher intracellular peak concentrations that might correlate with better anticancer effects, but also higher systemic drug exposure and safety issues.
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Affiliation(s)
- Elsa Lilienberg
- Department of Pharmacy, Uppsala University , Box 580, 751 23 Uppsala, Sweden
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Loffroy R, Favelier S, Cherblanc V, Estivalet L. C-arm dual-phase cone-beam CT: a revolutionary real-time imaging modality to assess drug-eluting beads TACE success in liver cancer patients. Quant Imaging Med Surg 2013; 3:196-9. [PMID: 24040615 DOI: 10.3978/j.issn.2223-4292.2013.08.05] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Accepted: 08/27/2013] [Indexed: 11/14/2022]
Abstract
The advent of cone-beam computed tomography (CBCT) in the angiography suite has been revolutionary in interventional radiology. CBCT offers 3 dimensions (3D) diagnostic imaging in the interventional suite and can enhance minimally-invasive therapy beyond the limitations of 2D angiography alone. The role of CBCT has been recognized in transcatheter arterial chemoembolization (TACE) treatment of liver cancer especially with the recent introduction of dual-phase CBCT (DP-CBCT) for unresectable hepatocellular carcinoma (HCC) treatment. Loffroy and colleagues proposed the use of intraprocedural C-arm DP-CBCT immediately after TACE with doxorubicin-eluting beads to predict HCC tumor response at 1-month magnetic resonance (MR) imaging follow-up. They reported a significant relationship between tumor enhancement seen at DP-CBCT after TACE and objective MR imaging response at 1-month follow-up, suggesting that DP-CBCT can be used to predict tumor response after TACE. If confirmed in larger studies, this imaging modality may play a key role in the improvement of treatment planning, especially with regard to the need for repeat treatment. More important, a potential clinical implication of using intraprocedural DP-CBCT in these patients might be elimination of 1-month follow-up MR imaging.
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Affiliation(s)
- Romaric Loffroy
- Department of Vascular, Oncologic and Interventional Radiology, Le2i, UMR CNRS 6306, University of Dijon School of Medicine, Bocage Teaching Hospital, 14 Rue Paul Gaffarel, BP 77908, 21079 Dijon Cedex, France
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Muros-Ortega M, Díaz-Carrasco MS, Capel A, Calleja MÁ, Martínez F. Effectiveness and safety of doxorubicin loaded beads in hepatocellular carcinoma. Int J Clin Pharm 2013; 35:1105-12. [DOI: 10.1007/s11096-013-9831-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Accepted: 07/22/2013] [Indexed: 02/08/2023]
Affiliation(s)
- María Muros-Ortega
- Pharmacy Department, Fresenius Medical Care Services Murcia SL, C/Valle de Ordesa, 45, 30740, San Pedro del Pinatar, Murcia, Spain,
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Kalva SP, Pectasides M, Liu R, Rachamreddy N, Surakanti S, Yeddula K, Ganguli S, Wicky S, Blaszkowsky LS, Zhu AX. Safety and effectiveness of chemoembolization with drug-eluting beads for advanced-stage hepatocellular carcinoma. Cardiovasc Intervent Radiol 2013; 37:381-7. [PMID: 23754191 DOI: 10.1007/s00270-013-0654-7] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 05/01/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, patients with advanced stage (BCLC-C) hepatocellular carcinoma (HCC) are recommended for systemic treatment or palliative therapy. However, chemoembolization with drug-eluting beads (DEB-TACE) has been shown to be safe in high-risk patients. The purpose of our study was to evaluate the safety and effectiveness of DEB-TACE in patients with an advanced-stage HCC. METHODS In this institutional review board-approved, retrospective study, 80 patients with advanced-stage HCC underwent DEB-TACE with doxorubicin. Patients were evaluated for median hospital stay, incidence of Grade 3/4 toxicities, 30-day mortality, progression-free survival (PFS), and overall survival (OS) following DEB-TACE. Univariate and multivariate analysis were performed for predictors of better OS. RESULTS The median hospital stay following DEB-TACE was 1 day (range: 1-11). The median PFS and OS were 5.1 months [95% confidence interval (CI): 4.1-7.7] and 13.3 months (95% CI: 10.1-18.6) respectively. On multivariate analysis ECOG PS ≤ 1 and >2 DEB-TACE procedures were associated with better OS. Patients with ECOG PS ≤ 1 demonstrated a median survival of 17.7 months compared with 5.6 months for patients with ECOG PS > 1 (p = 0.025). Multiple DEB-TACE procedures (>2 procedures) were associated with improved survival (26.8 months) compared with patients with one or two procedures (11.4 months, p = 0.01). Portal vein thrombosis or extrahepatic disease had no statistically significant association with OS. CONCLUSIONS DEB-TACE is safe and effective in patients with advanced HCC. ECOG PS ≤ 1 and >2 DEB-TACE procedures were associated with better OS.
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Affiliation(s)
- Sanjeeva P Kalva
- Interventional Radiology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8834, USA,
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GREGORY SM, MUNNEKE GJ. Interventional radiology in liver cancer. IMAGING 2013. [DOI: 10.1259/imaging.20120010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Giunchedi P, Maestri M, Gavini E, Dionigi P, Rassu G. Transarterial chemoembolization of hepatocellular carcinoma. Agents and drugs: an overview. Part 1. Expert Opin Drug Deliv 2013; 10:679-90. [PMID: 23406440 DOI: 10.1517/17425247.2013.770733] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most common lethal malignancies. The prognosis is poor despite progress in early diagnosis. The initial treatment of choice is hepatic resection; unfortunately, not all patients are eligible for liver resection. Moreover, there are significant recurrences. Different liver-directed therapies have been developed to increase the number of patients eligible for liver resection. Among them, transarterial chemoembolization (TACE) is a technique of improving importance that involves the intra-arterial administration of anticancer drugs and embolization agents into the liver tumor. In the first part of this review, an overview of the present situation in the field of TACE has been made, referring in particular to the use of Lipiodol. AREAS COVERED Clinical overview of TACE with attention to the present limits and problems of this technique. EXPERT OPINION The use of TACE techniques is important in the treatment of HCCs. However, this technique needs to be improved in particular taking into account the use of new materials for the preparation of embolizing agents able to control the drug release.
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Affiliation(s)
- Paolo Giunchedi
- University of Sassari, Department of Chemistry and Pharmacy, Sassari, Italy.
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Song DS, Choi JY, Yoo SH, Kim HY, Song MJ, Bae SH, Yoon SK, Chun HJ, Choi BG, Lee HG. DC Bead Transarterial Chemoembolization Is Effective in Hepatocellular Carcinoma Refractory to Conventional Transarteral Chemoembolization: A Pilot Study. Gut Liver 2013; 7:89-95. [PMID: 23424047 PMCID: PMC3572326 DOI: 10.5009/gnl.2013.7.1.89] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Revised: 06/08/2012] [Accepted: 06/26/2012] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND/AIMS To determine if hepatocellular carcinoma refractory to conventional transarterial chemoembolization (TACE) responds to TACE with DC beads. METHODS Between July 2008 to June 2010, 435 patients underwent TACE. Of these, 10 patients who had tumors refractory to conventional TACE and who thus were treated with TACE with DC beads were enrolled in this study. The treatment response after TACE with DC beads was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the Response Evaluation Criteria in Cancer of the Liver (RECICL). RESULTS Ten tumors were treated in 10 patients. Using the mRECIST and the RECICL, a complete response was observed in four (40%) of the tumors, and six tumors (60%) showed a partial response. Eight (80%) out of 10 HCCs showed delayed enhancement patterns upon angiography, and better responses were observed in these cases following DC bead treatment. The adverse effects of treatment with DC beads became tolerable. CONCLUSIONS TACE with DC beads was effective for HCCs refractory to conventional TACE, and this treatment elicited a better response, especially when the tumors were small and showed a delayed enhancement pattern upon angiography.
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Affiliation(s)
- Do Seon Song
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jong Young Choi
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sun Hong Yoo
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Myeong Jun Song
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Si Hyun Bae
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Ho Jong Chun
- Department of Radiology, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Byung Gil Choi
- Department of Radiology, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hae Giu Lee
- Department of Radiology, The Catholic University of Korea College of Medicine, Seoul, Korea
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Lewis AL, Holden RR, Chung ST, Czuczman P, Kuchel T, Finnie J, Porter S, Foster D. Feasibility, safety and pharmacokinetic study of hepatic administration of drug-eluting beads loaded with irinotecan (DEBIRI) followed by intravenous administration of irinotecan in a porcine model. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2013; 24:115-127. [PMID: 23015264 PMCID: PMC3540360 DOI: 10.1007/s10856-012-4768-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/27/2012] [Accepted: 09/17/2012] [Indexed: 06/01/2023]
Abstract
Irinotecan eluting embolization beads (DEBIRI) are currently being evaluated in the clinic for the treatment of colorectal cancer metastases to the liver. The aim of this study was to determine the safety and pharmacokinetics associated with two cycles of hepatic embolization using DEBIRI followed by intravenous administration of irinotecan. Pigs were embolized with DEBIRI (100-300 μm, 100 mg dose, n = 6) and blood samples taken over 24 h to determine plasma levels of irinotecan and SN-38 metabolite and for haematology and biochemistry. At 24 h an IV infusion of 250 mg/m(2) of irinotecan was administered and the plasma levels taken again. This cycle was repeated 3 weeks later. A single animal was subjected to a more aggressive regimen of embolization with 200 mg bead dose and IV of 350 mg/m(2) for two cycles. Three animals were sacrificed at 6 weeks and the remaining four (n = 3 standard dose, n = 1 high dose) animals at 12 weeks and detailed histopathology performed. All animals tolerated the treatments well, with only minor changes in haematological and biochemical parameters. There was no overlap in drug plasma levels observed from the bead and IV treatments when given 24 h apart and no difference between the pharmacokinetic profiles of the two cycles separated by 3 weeks. Irinotecan plasma AUC values were similar in both the embolization and IV arms of the study. C(max) values obtained during the IV arms of the study are approximately double that of the embolization arms whilst T(max) times are shorter in the IV arms, supporting extended release of drug from the beads. Bioavailability for bead-based delivery was double that for IV administration, which was attributed to reduced clearance of the drug when delivered by this route. No additive toxicity was observed as a consequence of the combined treatments. The combination of irinotecan delivery via drug eluting bead and IV was well-tolerated with no significant clinical effects. Pharmacokinetic analyses suggest the bioavailability from bead-based delivery of drug is double that of IV infusion, attributable to reduced drug clearance for the former.
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Affiliation(s)
- Andrew L Lewis
- Drug Delivery Division, Biocompatibles UK Ltd, Farnham Business Park, Weydon Lane, Farnham, Surrey, UK.
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Song MJ, Chun HJ, Song DS, Kim HY, Yoo SH, Park CH, Bae SH, Choi JY, Chang UI, Yang JM, Lee HG, Yoon SK. Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma. J Hepatol 2012; 57:1244-1250. [PMID: 22824821 DOI: 10.1016/j.jhep.2012.07.017] [Citation(s) in RCA: 195] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Revised: 06/29/2012] [Accepted: 07/12/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Transarterial chemoembolization (TACE) is a widely used treatment for hepatocellular carcinoma. In order to maximize its therapeutic efficacy, doxorubicin-loaded drug-eluting beads have been developed to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. The purpose of this study was to evaluate the efficacy and safety of drug-eluting bead (DC bead®) TACE in comparison with conventional TACE (cTACE). METHODS A total of 129 patients who underwent TACE between August 2008 and February 2011 were enrolled. We compared HCC patients who underwent TACE with DC bead® (n=60) to controls who received cTACE (n=69). The primary end points were treatment response and treatment-related adverse events. The secondary end point was time to progression. RESULTS The treatment response in the DC bead® group was significantly higher than that of the cTACE group (p<0.001). The time to progression was significantly better in the DC bead® group than in the cTACE group (11.7 and 7.6months, respectively, p=0.018). Subgroup analysis showed that in intermediate-stage HCC, DC bead® treatment resulted in a significantly better treatment response and longer time to progression than cTACE (p<0.001 and 0.038, respectively). However, there was no statistically significant difference in liver toxicity between the DC bead® and cTACE group (p>0.05). CONCLUSIONS TACE with DC bead® showed better treatment response and delayed tumor progression compared with cTACE. There was no significant difference in hepatic treatment-related toxicities. DC bead® TACE thus appears to be a feasible and promising approach to the treatment of HCC.
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Affiliation(s)
- Myeong Jun Song
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Vadot L, Boulin M, Malbranche C, Guiu B, Aho S, Musat A, Pernot C, Guignard MH, Hillon P, Fagnoni P. Result and cost of hepatic chemoembolisation with drug eluting beads in 21 patients. Diagn Interv Imaging 2012; 94:53-9. [PMID: 23146417 DOI: 10.1016/j.diii.2012.05.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
PURPOSE The aim of our study was to assess the results and cost of a treatment strategy involving transarterial chemoembolisation with drug eluting beads (DEB-TACE) in patients with unresectable non-metastatic hepatocellular carcinoma (HCC). PATIENTS AND METHODS This study included all patients treated with DEB-TACE in our hospital between January 2009 and December 2010. All patients received DEB-TACE on demand and were evaluated after each session. RESULTS Twenty-one patients received an average of 1.3 sessions. The median time to treatment discontinuation and median progression-free survival was 181 days and 295 days, respectively. Toxicity caused treatment discontinuation in three patients (14%). For the hospital, the average direct cost of treatment was €6,033 according to the analytical accounting system vs. €4,558 according to the official tariffs from the new French Diagnosis-Related Group prospective payment system (P=0.002). CONCLUSION In the treatment of HCC, on-demand DEB-TACE stabilises the disease in some patients but has not yet been thoroughly evaluated.
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Affiliation(s)
- L Vadot
- Pôle Pharmacie, CHU de Dijon, Bocage Central, 14, rue Gaffarel, 21000 Dijon, France.
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Loffroy R, Lin M, Yenokyan G, Rao PP, Bhagat N, Noordhoek N, Radaelli A, Blijd J, Liapi E, Geschwind JF. Intraprocedural C-arm dual-phase cone-beam CT: can it be used to predict short-term response to TACE with drug-eluting beads in patients with hepatocellular carcinoma? Radiology 2012; 266:636-48. [PMID: 23143027 DOI: 10.1148/radiol.12112316] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE To investigate whether C-arm dual-phase cone-beam computed tomography (CT) performed during transcatheter arterial chemoembolization (TACE) with doxorubicin-eluting beads can help predict tumor response at 1-month follow-up in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This prospective study was compliant with HIPAA and approved by the institutional review board and animal care and use committee. Analysis was performed retrospectively on 50 targeted HCC lesions in 29 patients (16 men, 13 women; mean age, 61.9 years ± 10.7) treated with TACE with drug-eluting beads. Magnetic resonance (MR) imaging was performed at baseline and 1 month after TACE. Dual-phase cone-beam CT was performed before and after TACE. Tumor enhancement at dual-phase cone-beam CT in early arterial and delayed venous phases was assessed retrospectively with blinding to MR findings. Tumor response at MR imaging was assessed according to European Association for the Study of the Liver (EASL) guidelines. Two patients were excluded from analysis because dual-phase cone-beam CT scans were not interpretable. Logistic regression models for correlated data were used to compare changes in tumor enhancement between modalities. The radiation dose with dual-phase cone-beam CT was measured in one pig. RESULTS At 1-month MR imaging follow-up, complete and/or partial tumor response was seen in 74% and 76% of lesions in the arterial and venous phases, respectively. Paired t tests used to compare images obtained before and after TACE showed a significant reduction in tumor enhancement with both modalities (P < .0001). The decrease in tumor enhancement seen with dual-phase cone-beam CT after TACE showed a linear correlation with MR findings. Estimated correlation coefficients were excellent for first (R = 0.89) and second (R = 0.82) phases. A significant relationship between tumor enhancement at cone-beam CT after TACE and complete and/or partial tumor response at MR imaging was found for arterial (odds ratio, 0.95; 95% confidence interval [CI]: 0.91, 0.99; P = .023) and venous (odds ratio, 0.96; 95% CI: 0.93, 0.99; P = .035) phases with the multivariate logistic regression model. Radiation dose for two dual-phase cone-beam CT scans was 3.08 mSv. CONCLUSION Intraprocedural C-arm dual-phase cone-beam CT can be used immediately after TACE with doxorubicin-eluting beads to predict HCC tumor response at 1-month MR imaging follow-up.
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Affiliation(s)
- Romaric Loffroy
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Sheikh Zayed Tower, Ste 7203, 1800 Orleans St, Baltimore, MD 21287, USA
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Guibal A, Lefort T, Chardon L, Benslama N, Mulé S, Pilleul F, Lombard-Bohas C, Bridal L, Chayvialle JA, Lucidarme O, Denys A, Walter T. Contrast-enhanced ultrasound after devascularisation of neuroendocrine liver metastases: functional and morphological evaluation. Eur Radiol 2012; 23:805-15. [PMID: 23001579 DOI: 10.1007/s00330-012-2646-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Revised: 08/05/2012] [Accepted: 08/09/2012] [Indexed: 01/23/2023]
Abstract
OBJECTIVE To evaluate morphological and perfusion changes in liver metastases of neuroendocrine tumours by contrast-enhanced ultrasound (CEUS) after transarterial embolisation with bead block (TAE) or trans-arterial chemoembolisation with doxorubicin-eluting beads (DEB-TACE). METHODS In this retrospective study, seven patients underwent TAE, and ten underwent DEB-TACE using beads of the same size. At 1 day before embolisation, 2 days, 1 month and 3 months after the procedure, a destruction-replenishment study using CEUS was performed with a microbubble-enhancing contrast material on a reference tumour. Relative blood flow (rBF) and relative blood volume (rBV) were obtained from the ratio of values obtained in the tumour and in adjacent liver parenchyma. Morphological parameters such as the tumour's major diameter and the viable tumour's major diameter were also measured. A parameter combining functional and morphological data, the tumour vitality index (TVI), was studied. The Wilcoxon rank-sum test and Fisher's test were used to compare treatment groups. RESULTS At 3 months rBF, rBV and TVI were significantly lower (P = 0.005, P = 0.04 and P = 0.03) for the group with doxorubicin. No difference in morphological parameters was found throughout the follow-up. CONCLUSIONS One parameter, TVI, could evaluate the morphological and functional response to treatments.
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Affiliation(s)
- Aymeric Guibal
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Imagerie Digestive, 69437 Lyon cedex 03, France.
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Seinstra BA, Defreyne L, Lambert B, Lam MGEH, Verkooijen HM, van Erpecum KJ, van Hoek B, van Erkel AR, Coenraad MJ, Al Younis I, van Vlierberghe H, van den Bosch MAAJ. Transarterial radioembolization versus chemoembolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial. Trials 2012; 13:144. [PMID: 22913492 PMCID: PMC3493260 DOI: 10.1186/1745-6215-13-144] [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: 01/12/2012] [Accepted: 08/09/2012] [Indexed: 02/08/2023] Open
Abstract
Background Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization (90Y-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor. 90Y-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and 90Y-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma. Methods/design In this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either 90Y-RE or TACE with drug eluting beads. Patients assigned to 90Y-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease. Patients assigned to TACE will receive a maximum of three consecutive transarterial treatment sessions. Patients will undergo structural follow-up for a timeframe of two years post treatment. Post procedural magnetic resonance imaging (MRI) will be performed at one and three months post trial entry and at three-monthly intervals thereafter for two years to assess tumor response. Primary outcome will be time to progression. Secondary outcomes will be overall survival, tumor response according to the modified RECIST criteria, toxicities/adverse events, treatment related effect on total liver function, quality of life, treatment-related costs and cost-effectiveness. Trial registration NCT01381211
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Affiliation(s)
- Beatrijs A Seinstra
- Department of Radiology, University Medical Center Utrecht, Room E.01.132, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
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Kritzinger J, Klass D, Ho S, Lim H, Buczkowski A, Yoshida E, Liu D. Hepatic embolotherapy in interventional oncology: technology, techniques, and applications. Clin Radiol 2012; 68:1-15. [PMID: 22917735 DOI: 10.1016/j.crad.2012.06.112] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Revised: 05/27/2012] [Accepted: 06/01/2012] [Indexed: 01/17/2023]
Abstract
Embolotherapy continues to play a growing role in the management of primary and secondary hepatic malignancies. In this review article, we examine the basis of therapy with a focus on neovascularization, which makes treatments via the hepatic artery possible. An overview of the three generations of embolic and therapeutic agents follows. The techniques, technologies, and complications of bland embolization, transarterial chemoembolization, drug-eluting beads, and selective internal radiotherapy are covered to give the reader an overview of this exciting field in interventional radiology.
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Affiliation(s)
- J Kritzinger
- Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada.
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