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1
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Solbiati LA, Arai Y. Interventional oncology of liver tumors: how it all started and where are we now. Br J Radiol 2022; 95:20220434. [PMID: 35776630 PMCID: PMC9815741 DOI: 10.1259/bjr.20220434] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/22/2022] [Accepted: 06/28/2022] [Indexed: 01/13/2023] Open
Abstract
Liver was the very first organ for which interventional procedures were applied for the local treatment of primary and secondary malignancies. In this paper, the history of Interventional Oncology of liver, from the very beginning to the current situation, is summarized, including both percutaneous and intravascular procedures, and together with the evolution of the techniques for image guidance. The main ongoing developments, such as new techniques, combined interventional treatments and association of local interventions with new drugs are briefly described, too.
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Affiliation(s)
| | - Yasuaki Arai
- Department of Diagnostic Radiology, National Cancer Center, Tokyo, Japan
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2
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Cheung TT, Ma KW, She WH. A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis. Hepatobiliary Surg Nutr 2021; 10:193-209. [PMID: 33898560 DOI: 10.21037/hbsn.2020.03.11] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Importance Hepatocellular carcinoma (HCC) is usually accompanied by liver cirrhosis, which makes treatment of this disease challenging. Liver transplantation theoretically provides an ultimate solution to the disease, but the maximal surgical stress and the scarcity of liver graft make this treatment option impossible for some patients. In an ideal situation, a treatment that is safe and effective should provide a better outcome for patients with the dilemma. Objective This article aims to give a comprehensive review of various types of loco-ablative treatment for HCC. Evidence Review Loco-ablative treatment bridges the gap between surgical resection and transarterial chemotherapy. Various types of ablative therapy have their unique ability, and evidence-based outcome analysis is the most important key to assisting clinicians to choose the most suitable treatment modality for their patients. Findings Radiofrequency ablation (RFA) has a relatively longer history and more evidence to support its effectiveness. Microwave ablation (MWA) is gaining momentum because of its shorter ablation time and consistent ablation zone. High-intensity focused ultrasound (HIFU) ablation is a relatively new technology that provides non-invasive treatment for patients with HCC. It has been carried out at centers of excellence and it is a safe and effective treatment option for selected patients with HCC and liver cirrhosis. Conclusion and Relevance Selective use of different loco-ablative therapies will enhance clinicians' treatment options for treatment of HCC.
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Affiliation(s)
- Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Ka Wing Ma
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
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3
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Tan T, Shen Z, Wang Y, Guo Z, Hu J, Zhang Y. Self-assembly of pentapeptides in ethanol to develop organogels. SOFT MATTER 2020; 16:10567-10573. [PMID: 33079116 DOI: 10.1039/d0sm01303j] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Organogels have a wide variety of applications in the fields of chemistry, electricity, biomedicine and environmental engineering, which call for robust strategies for designing and developing novel organogelators. Here, we reported a pentapeptide, ECAYF, which was capable of forming a self-healing ethanol gel exhibiting viscoelastic and solid-like properties. The ethanol gel of ECAYF was stable for at least several months, suggesting strong non-covalent interactions between ethanol and the peptide in the gel. In the ethanol gel, self-assembled peptide fibrils were found to immobilize the ethanol molecules for gelation. Results also suggested that the EAF-5 peptide adopted H-bonding β-sheet secondary structures, which further assembled into fibrils. Meanwhile, the self-assembly of the ECAYF peptide in mixtures of differently fractioned ethanol and H2O was observed, which clearly indicated that ethanol promoted the assembly of ECAYF in the solutions. These findings are helpful in understanding the roles of organic solvents as well as the complicated interactions between the solvent and gelator molecules in gelation.
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Affiliation(s)
- Tingyuan Tan
- Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
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4
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Imajo K, Ogawa Y, Yoneda M, Saito S, Nakajima A. A review of conventional and newer generation microwave ablation systems for hepatocellular carcinoma. J Med Ultrason (2001) 2020; 47:265-277. [PMID: 31960190 DOI: 10.1007/s10396-019-00997-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 11/21/2019] [Indexed: 12/15/2022]
Abstract
Although microwave ablation (MWA) exhibits a high thermal efficiency, the major limitation of conventional MWA systems is the lack of predictability of the ablation zone size and shape. Therefore, a specific newer generation MWA system, The Emprint™ Ablation System with Thermosphere™ Technology, was designed to create predictable large spherical zones of ablation that are not impacted by varying tissue environments. The time required for ablation with MWA systems is short, and the shape of the necrosis is elliptical with the older systems and spherical with the new system. In addition, because MWA has no heat-sink effect, it can be used to ablate tumors adjacent to major vessels. Although these factors yield a large ablation volume and result in good local control, excessive ablation of liver tissue and unexpected ablation of surrounding organs are possible. Therefore, MWA should be carefully performed. This review highlights the efficacy and complications of MWA performed with conventional systems and the newer generation system in patients with hepatocellular carcinoma (HCC). MWA with the newer generation system seems to be a promising treatment option for large HCCs and secondary hepatic malignancies, with several advantages over other available ablation techniques, including conventional MWA. However, further randomized controlled trials are necessary to fully clarify the benefits and pitfalls of this new system.
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Affiliation(s)
- Kento Imajo
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Yuji Ogawa
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Satoru Saito
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
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5
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Xie L, Cao F, Qi H, Song Z, Shen L, Chen S, Hu Y, Chen C, Fan W. Efficacy and safety of CT-guided percutaneous thermal ablation for hepatocellular carcinoma adjacent to the second porta hepatis. Int J Hyperthermia 2019; 36:1122-1128. [DOI: 10.1080/02656736.2019.1684575] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Affiliation(s)
- Lin Xie
- Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Fei Cao
- Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Han Qi
- Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Ze Song
- Department of Oncology, The Seventh Affiliated Hospital,Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Lujun Shen
- Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Shuanggang Chen
- Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Yubin Hu
- Department of Interventional Radiology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China
| | - Chao Chen
- Department of Interventional Therapy, The Second Hospital of Shandong University, Jinan, Shandong, China
| | - Weijun Fan
- Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
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6
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Galanakis N, Kehagias E, Matthaiou N, Samonakis D, Tsetis D. Transcatheter arterial chemoembolization combined with radiofrequency or microwave ablation for hepatocellular carcinoma: a review. Hepat Oncol 2018; 5:HEP07. [PMID: 31293775 PMCID: PMC6613040 DOI: 10.2217/hep-2018-0001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Accepted: 06/19/2018] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common type of malignancy. Several therapies are available for HCC and are determined by stage of presentation, patient clinical status and liver function. Local–regional treatment options, including transcatheter arterial chemoembolization, radiofrequency ablation or microwave ablation, are safe and effective for HCC but are accompanied by limitations. The synergistic effects of combined transcatheter arterial chemoembolization and radiofrequency ablation/microwave ablation may overcome these limitations and improve the therapeutic outcome. The purpose of this article is to review the current literature on these combined therapies and examine their efficacy, safety and influence on the overall and recurrence-free survival in patients with HCC.
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Affiliation(s)
- Nikolaos Galanakis
- Interventional Radiology Unit, Department of Radiology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece.,Interventional Radiology Unit, Department of Radiology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece
| | - Elias Kehagias
- Interventional Radiology Unit, Department of Radiology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece.,Interventional Radiology Unit, Department of Radiology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece
| | - Nikolas Matthaiou
- Interventional Radiology Unit, Department of Radiology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece.,Interventional Radiology Unit, Department of Radiology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece
| | - Dimitrios Samonakis
- Department of Gastroenterology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece.,Department of Gastroenterology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece
| | - Dimitrios Tsetis
- Interventional Radiology Unit, Department of Radiology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece.,Interventional Radiology Unit, Department of Radiology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion, P.C. 71110, Greece
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7
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Ham SJ, Choi Y, Lee SI, Kim J, Kim YI, Chung JW, Kim KW. Enhanced efficacy of radiofrequency ablation for hepatocellular carcinoma using a novel vascular disrupting agent, CKD-516. Hepatol Int 2017; 11:446-451. [PMID: 28721452 DOI: 10.1007/s12072-017-9811-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Accepted: 06/13/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND CKD-516 is a novel vascular disrupting agent that shuts down intratumoral blood flow. We therefore hypothesized that concomitant administration of CKD-516 would enhance the therapeutic efficacy of radiofrequency ablation (RFA) by reducing heat sink effects. We assessed the effects of the combination of CKD-516 and RFA in a rat orthotopic hepatocellular carcinoma (HCC) model. METHODS Rat HCC cells (N1-S1) were engrafted into the hepatic lobe of Sprague-Dawley (SD) rats. Mice were randomly divided into two groups: RFA-only and CKD-RFA. In the CKD-RFA group, CKD-516 was administered by intraperitoneal injection 2 h before RFA. Ablation zone size was measured on triphenyltetrazolium chloride-stained specimens. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to evaluate the area of apoptosis/necrosis in the ablation zone. Immunohistochemistry with anti-CD31 antibody was performed to evaluate the effect of CKD-516 on tumor vessels. RESULTS Ablation zone size was significantly larger in the CKD-RFA group than in the RFA-only group (243.10 ± 74.39 versus 123.30 ± 28.17 mm2, p < 0.001). On TUNEL staining, the area of apoptosis/necrosis was also significantly larger in the CKD-RFA group than in the RFA-only group (274.44 ± 140.78 versus 143.74 ± 90.13 mm2; p = 0.006). Immunohistochemistry with anti-CD31 antibody revealed patent tumor vessels in the RFA-only group, while collapsed vessels were seen in the CKD-RFA group, indicating a vascular shutdown effect of CKD-516. CONCLUSION Concomitant administration of CKD-516 during RFA can increase the ablation zone of tumors due to its vascular disrupting effect.
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Affiliation(s)
- Su Jung Ham
- Bioimaging Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.,Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea
| | - YoonSeok Choi
- Biomedical Translational Research Center, GangNeung Asan Medical Center, Sacheon-myoen, Bangdong-kil 38, GangNeung, Gangwon, 210-711, Korea.,Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
| | - Seul-I Lee
- Bioimaging Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.,Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea
| | - Jinil Kim
- Bioimaging Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.,Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea
| | - Young Il Kim
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
| | - Kyung Won Kim
- Bioimaging Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. .,Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
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8
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Sheta E, El-Kalla F, El-Gharib M, Kobtan A, Elhendawy M, Abd-Elsalam S, Mansour L, Amer I. Comparison of single-session transarterial chemoembolization combined with microwave ablation or radiofrequency ablation in the treatment of hepatocellular carcinoma: a randomized-controlled study. Eur J Gastroenterol Hepatol 2016; 28:1198-1203. [PMID: 27362551 DOI: 10.1097/meg.0000000000000688] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Globally, hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related mortality. In recent years, transarterial chemoembolization, radiofrequency ablation, and microwave ablation (MWA) have been accepted as treatment modalities for patients with surgically unresectable HCC. AIM OF THIS WORK This study aimed to compare combination treatment with radiofrequency or MWA, followed by transarterial chemoembolization, and performed in a single session. PATIENTS AND METHODS This study was carried out on 50 patients with nonresectable single-lesion HCC, who were divided into three groups: group A included 20 patients treated by transcatheter hepatic arterial chemoembolization, group B included 20 patients treated by radiofrequency thermal ablation combined with transcatheter arterial chemoembolization, and group C included 10 patients treated by MWA combined with transcatheter arterial chemoembolization. The combined treatments were performed in a single session, with the ablation performed first. RESULTS The total success rate in this study at 6 months following the procedure was 50% in group A, 70% in group B, and 80% in group C. Major complications were recorded in 22% of patients. The number of complications was the highest in group A. CONCLUSION Combined ablation with chemoembolization is superior in the treatment of nonresectable single masses larger than 4 cm. Transcatheter arterial chemoembolization and ablation can be performed safely and successfully during a single session, which has not been found to decrease the response rates to treatment. Combined treatment with MWA is more effective in terms of tumor response, and results in the same complication rate as with radiofrequency, but less than chemoembolization alone.
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Affiliation(s)
- Elshazly Sheta
- aDepartment of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta bDepartment of Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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9
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Azuma S, Asahina Y, Nishimura-Sakurai Y, Kakinuma S, Kaneko S, Nagata H, Goto F, Ootani S, Kawai-Kitahata F, Taniguchi M, Murakawa M, Watanabe T, Tasaka-Fujita M, Itsui Y, Nakagawa M, Watanabe M. Efficacy of additional radiofrequency ablation after transcatheter arterial chemoembolization for intermediate hepatocellular carcinoma. Hepatol Res 2016. [PMID: 26224167 DOI: 10.1111/hepr.12566] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM For intermediate hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) therapy is recommended in the guidelines as a monotherapy, although TACE is a non-curative therapy. The aims of the present study were to evaluate the efficacy of adding radiofrequency ablation (RFA) to TACE in patients with intermediate HCC, and to identify the factors that were associated with favorable survival in these patients. METHODS Fifty-nine patients with intermediate HCC were enrolled in this retrospective study. Thirty-nine patients were treated with TACE alone and 20 patients were treated with additional RFA after TACE. RESULTS The recurrence-free survival rates at 0.5, 1 and 2 years for the additional RFA group were 32%, 19% and 13%, respectively, and these were significantly higher than those of the TACE group (8%, 3% and 0%, respectively; log-rank test, P = 0.001). The cumulative survival rates of the additional RFA group were significantly higher than those of the TACE group (log-rank test, P = 0.002), although this significant difference was not found in the subgroup of treatment naive patients because of small sample size. Multivariate analysis indicated male sex, lower total bilirubin, lower α-fetoprotein, lower des-γ-carboxyprothrombin, newly recurrent HCC nodules within the last 12 months and additional RFA as independent factors that were significantly associated with favorable overall survival. CONCLUSION Additional RFA of nodules insufficiently treated by TACE is effective therapy for obtaining favorable disease-free survival in patients with intermediate HCC, and leads to better overall survival particularly in recurrent patients.
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Affiliation(s)
- Seishin Azuma
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuki Nishimura-Sakurai
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sei Kakinuma
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shun Kaneko
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroko Nagata
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Fumio Goto
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Satoshi Ootani
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Fukiko Kawai-Kitahata
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Miki Taniguchi
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Miyako Murakawa
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takako Watanabe
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Megumi Tasaka-Fujita
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Itsui
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mina Nakagawa
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mamoru Watanabe
- Departments of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
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10
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Duan XH, Li YS, Han XW, Wang YL, Jiao DC, Li TF, Chen PF, Fang Y. C-arm CT-guided renal arterial embolisation followed by radiofrequency ablation for treatment of patients with unresectable renal cell carcinoma. Clin Radiol 2015; 71:79-85. [PMID: 26602936 DOI: 10.1016/j.crad.2015.10.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 09/29/2015] [Accepted: 10/14/2015] [Indexed: 01/20/2023]
Abstract
AIM To explore the value of using flat detector (FD) equipped angiographic C-arm CT (CACT) systems in treating unresectable renal cell carcinoma (RCC) by selective renal arterial embolisation (RAE) followed by radiofrequency ablation (RFA) (RAE-RFA). MATERIALS AND METHODS A total of 28 patients who were not candidates for surgery were enrolled. The average size of tumours was 6.7±2.2 cm (range 4.1-9.6 cm). Twenty-eight tumours were treated with CACT-guided RFA, 5-7 days after CACT-guided RAE. RESULTS CACT-guided RAE-RFA was technically successful in all patients. Tumour enhancement disappeared after a single RAE-RFA session in 20 patients, after two RAE-RFA sessions in four patients and after three RAE-RFA sessions in the other four patients. One patient died of lung metastasis and haematuria 13 months after RAE-RFA, and another patient died of pulmonary heart disease 23 months after repeat RAE-RFA. In the 26 living patients, tumours remained controlled during a mean follow-up period of 27 months and showed significant reduction in tumour size (6.7±2.2 cm to 3.9±1.7 cm, p<0.01). There were no significant changes in creatinine levels or urea nitrogen concentrations before and after the last RAE-RFA (p>0.05). There were no serious complications during and after the procedure. CONCLUSION CACT-guided RAE followed by RFA appears to be a safe and effective technique for treating patients with inoperable RCC.
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Affiliation(s)
- X-H Duan
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Y-S Li
- Department of Urology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - X-W Han
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China.
| | - Y-L Wang
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - D-C Jiao
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - T-F Li
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - P-F Chen
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Y Fang
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People's Republic of China
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11
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Morishita A, Sakamoto T, Kobara H, Tadokoro T, Ohura K, Fujita K, Tani J, Miyoshi H, Yoneyama H, Himoto T, Masaki T. Evaluation of in vivo efficacy of radiofrequency ablation with D-sorbitol in animal liver. Mol Clin Oncol 2015; 4:183-186. [PMID: 26893857 DOI: 10.3892/mco.2015.680] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Accepted: 08/12/2015] [Indexed: 11/06/2022] Open
Abstract
Percutaneous radiofrequency ablation (RFA) enables cauterization of liver cancer in a limited number of sessions without major complications. In contrast to the efficacy of this technique, the size of coagulation necrosis is limited due to increased impedance. D-sorbitol has been used as an irrigating fluid during transurethral resection of the prostate, since it is considered to be a dielectric fluid. In order to determine whether D-sorbitol enhances the effect of RFA, RFA was performed by slowly injecting 3% D-sorbitol near the tip of the RFA needle. The maximum of the total injected volume of D-sorbitol was 20 ml and RFA was terminated if the threshold of impedance was exceeded. RFA and D-sorbitol RFA were performed in 5 different parts of pig livers and dog livers in vivo. The total volumes of coagulation necrosis in the D-sorbitol RFA group were significantly higher compared with those in the RFA group. The total delivered energy in the D-sorbitol RFA group was also higher compared with that in the RFA group, due to the suppression of impedance elevation. No significant complications, such as bleeding or damage, were observed during the D-sorbitol RFA procedure in the in vivo model. In conclusion, RFA combined with D-sorbitol increases the total volume of coagulation necrosis through controlling impedance in the ablated liver and, therefore, D-sorbitol may be useful for the treatment of liver cancers.
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Affiliation(s)
- Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
| | - Teppei Sakamoto
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
| | - Kyoko Ohura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
| | - Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
| | - Hisaaki Miyoshi
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectual University of Health Sciences, Takamatsu, Kagawa 761-0123, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa 761-0793, P.R. China
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Yin X, Zhang L, Wang YH, Zhang BH, Gan YH, Ge NL, Chen Y, Li LX, Ren ZG. Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate (BCLC B) hepatocellular carcinoma. BMC Cancer 2014; 14:849. [PMID: 25409554 PMCID: PMC4256894 DOI: 10.1186/1471-2407-14-849] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Accepted: 11/06/2014] [Indexed: 12/30/2022] Open
Abstract
Background This study was designed to evaluate the effectiveness of radiofrequency ablation in patients with intermediate (BCLC B) stage hepatocellular carcinoma who underwent transcatheter arterial chemoembolization. Methods Included in this study were 211 patients with intermediate stage HCC who underwent initial transcatheter arterial chemoembolization and were potentially amendable for radiofrequency ablation (single tumor with diameter 5-8 cm, median 6.0 cm; 2–5 multiple nodules with diameter less than 5 cm) between January 2005 and December 2011. According to the inclusion and exclusion criteria, 55 patients were treated with following radiofrequency ablation, and the remaining 156 patients were treated with transcatheter arterial chemoembolization alone. The treatment effectiveness, local tumor control and survival outcome between the two groups were compared. Results The complete tumor necrosis rate after treatment was 76.9% in combination group vs. 46.5% in transcatheter arterial chemoembolization alone group (P = 0.02). The major complication rate was 1.8% in combination group vs. 2.6% in transcatheter arterial chemoembolization alone group. Follow-up observation showed that the total tumor control rate was 74.5% in combination group versus 54.5% in transcatheter arterial chemoembolization alone group (P < 0.001). The 1-, 3- and 5-year survival rates in combination group were significantly higher than those in TACE alone group (P = 0.01). Conclusions Radiofrequency ablation following initial transcatheter arterial chemoembolization delays tumor progression and prolongs overall survival of patients with intermediate stage HCC tumors.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Zheng-Gang Ren
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, China.
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Yi Y, Zhang Y, Wei Q, Zhao L, Han J, Song Y, Ding Y, Lu G, Liu J, Ding H, Dai F, Tang X. Radiofrequency ablation or microwave ablation combined with transcatheter arterial chemoembolization in treatment of hepatocellular carcinoma by comparing with radiofrequency ablation alone. Chin J Cancer Res 2014; 26:112-8. [PMID: 24653633 DOI: 10.3978/j.issn.1000-9604.2014.02.09] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Accepted: 02/08/2014] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE To compare radiofrequency ablation (RFA) or microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) with RFA or MWA monotherapy in hepatocellular carcinoma (HCC). METHODS A prospective, randomized, controlled trial was conducted on 94 patients with HCC ≤7 cm at a single tertiary referral center from June 2008 to June 2010 at the Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Southeast University. The patients were randomly assigned into the TACE-RFA or TACE-MWA (combined treatment group) and the RFA-alone or MWA-alone groups (control group). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. RESULTS Until the time of censor, 17 patients in the TACE-RFA or TACE-MWA group had died. The median follow-up time of the patients who were still alive for the TACE-RFA or TACE-MWA group was 47.5±11.3 months (range, 29 to 62 months). The 1-, 3- and 5-year overall survival for the TACE-RFA or TACE-MWA group was 93.6%, 68.1% and 61.7%, respectively. Twenty-five patients in the RFA or MWA group had died. The median follow-up time of the patients who were still alive for the RFA or MWA group was 47.0±12.9 months (range, 28 to 62 months). The 1-, 3- and 5-year overall survival for the RFA or MWA group was 85.1%, 59.6% and 44.7%, respectively. The patients in the TACE-RFA or TACE-MWA group had better overall survival than the RFA or MWA group [hazard ratio (HR), 0.526; 95% confidence interval (95% CI), 0.334-0.823; P=0.002], and showed better recurrence-free survival than the RFA or MWA group (HR, 0.582; 95% CI, 0.368-0.895; P=0.008). CONCLUSIONS RFA or MWA combined with TACE in the treatment of HCC ≤7 cm was superior to RFA or MWA alone in improving survival by reducing arterial and portal blood flow due to TACE with iodized oil before RFA.
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Affiliation(s)
- Yongxiang Yi
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Yufeng Zhang
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Qiang Wei
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Liang Zhao
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Jianbo Han
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Yan Song
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Ying Ding
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Guilan Lu
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Junmao Liu
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Huaiying Ding
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Feng Dai
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
| | - Xiaojun Tang
- 1 Department of Hepatobiliary Surgery; 2 Department of Medical Imaging, the Second Affiliated Hospital of Southeast University, Nanjing 210003, China
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Zhang L, Yin X, Gan YH, Zhang BH, Zhang JB, Chen Y, Xie XY, Ge NL, Wang YH, Ye SL, Ren ZG. Radiofrequency ablation following first-line transarterial chemoembolization for patients with unresectable hepatocellular carcinoma beyond the Milan criteria. BMC Gastroenterol 2014; 14:11. [PMID: 24410841 PMCID: PMC3890612 DOI: 10.1186/1471-230x-14-11] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2013] [Accepted: 01/03/2014] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Recent studies suggest that a combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may have theoretical advantages over TACE alone for treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the effectiveness and safety of radiofrequency ablation following first-line TACE treatment in the management of HCC beyond the Milan Criteria. METHODS Forty-five patients who consecutively underwent RFA following first-line TACE treatment for HCC beyond the Milan criteria were enrolled in this study. RFA was performed within 1-2 months after TACE treatment in patients who had incomplete necrotic tumor nodules. Primary effectiveness, complications, survival rates, and prognostic factors were evaluated retrospectively. RESULTS Complete ablation was achieved in 76.2% of the lesions according to 1-month follow-up computed tomography/magnetic resonance imaging evaluation. The mean follow-up period was 30.9 months (range 3-94 months). There were no major complications after RFA therapy. The median overall survival was 29 months (range 20-38 months), with 1-, 2-, and 3-year survival of 89%, 61%, and 43%, respectively. Multivariate analysis revealed that tumor diameter (P = 0.045, hazard ratio [HR] = 0.228, 95% confidence interval [CI]: 0.054-0.968) and pretreatment serum alpha-fetoprotein level (P = 0.024, HR = 2.239, 95% CI: 1.114-4.500) were independent predictors for long-term survival. CONCLUSIONS HCC beyond the Milan criteria can be completely and safely ablated by radiofrequency ablation following first-line TACE treatment with a low rate of complications and favorable survival outcome. Further assessment of the survival benefits of combination treatment for HCCs beyond the Milan Criteria is warranted.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Zheng-Gang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Xue Yuan Road, Shanghai 20032, China.
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Ni JY, Liu SS, Xu LF, Sun HL, Chen YT. Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol 2013; 19:3872-3882. [PMID: 23840128 PMCID: PMC3699038 DOI: 10.3748/wjg.v19.i24.3872] [Citation(s) in RCA: 127] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Revised: 02/26/2013] [Accepted: 04/04/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA monotherapy in hepatocellular carcinoma (HCC).
METHODS: We searched PubMed, Medline, Embase and Chinese databases (CBMdisc and Wanfang data) for randomized controlled trails comparing RFA plus TACE and RFA alone for treatment of HCC from January 2000 to December 2012. The overall survival rate, recurrence-free survival rate, tumor progression rate, and safety were analyzed and compared. The analysis was conducted on dichotomous outcomes and the standard meta-analytical techniques were used. Pooled odds ratios (ORs) with 95%CIs were calculated using either the fixed-effects or random-effects model. For each meta-analysis, the χ2 and I2 tests were first calculated to assess the heterogeneity of the included trials. For P < 0.05 and I2 > 50%, the assumption of homogeneity was deemed invalid, and the random-effects model was used; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted using Review manager (version 4.2.2.) from the Cochrane collaboration.
RESULTS: Eight randomized controlled trials were identified as eligible for inclusion in this analysis and included 598 patients with 306 treated with RFA plus TACE and 292 with RFA alone. Our data analysis indicated that RFA plus TACE was associated a significantly higher overall survival rate (OR1-year = 2.96, 95%CI: 1.84-7.74, P < 0.001; OR2-year = 3.72, 95%CI: 1.24-11.16, P = 0.02; OR3-year = 2.65, 95%CI: 1.81-3.86, P < 0.001) and recurrence-free survival rate (OR3-year = 3.00, 95%CI: 1.75-5.13, P < 0.001; OR5-year = 2.26, 95%CI: 1.43-3.57, P = 0.0004) vs that of RFA alone. The tumor progression rate in patients treated with RFA alone was higher than that of RFA plus TACE (OR = 0.60, 95%CI: 0.42-0.88, P = 0.008) and there was no significant difference on major complications between two different kinds of treatment (OR = 1.20, 95%CI: 0.31-4.62, P = 0.79). Additionally, the meta-analysis data of subgroups revealed that the survival rate was significantly higher in patients with intermediate- and large-size HCC underwent RFA plus TACE than in those underwent RFA monotherapy; however, there was no significant difference between RFA plus TACE and RFA on survival rate for small HCC.
CONCLUSION: The combination of RFA with TACE has advantages in improving overall survival rate, and provides better prognosis for patients with intermediate- and large-size HCC.
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Ni JY, Liu SS, Xu LF, Sun HL, Chen YT. Transarterial chemoembolization combined with percutaneous radiofrequency ablation versus TACE and PRFA monotherapy in the treatment for hepatocellular carcinoma: a meta-analysis. J Cancer Res Clin Oncol 2013; 139:653-9. [PMID: 23292073 DOI: 10.1007/s00432-012-1369-x] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2012] [Accepted: 12/20/2012] [Indexed: 12/17/2022]
Abstract
PURPOSE This meta-analysis was designed to compare the effectiveness of the combination of transarterial chemoembolization (TACE) and percutaneous radiofrequency ablation (PRFA) with that of TACE and PRFA monotherapy in hepatocellular carcinoma (HCC). METHODS Randomized controlled trials were searched using various databases, and six studies were revealed on comparing TACE plus PRFA with TACE and/or PRFA alone for the treatment for HCC. Overall survival rate and recurrence-free survival rate were analyzed and compared. All statistic analyses were conducted using Review Manager (version 4.2.2.) from the Cochrane collaboration. RESULTS Meta-analysis data revealed that TACE plus PRFA had significantly better effectiveness on 1- and 3-year overall survival rate(odds ratio [OR] 1-year = 4.61, 95 % confidence interval [95 % CI] 2.26-9.42, P < 0.0001; OR 3-year = 2.79, 95 % CI 1.69-4.61, P < 0.0001) and 3-year recurrence-free survival rate ([OR] 3-year = 3.00, [95 % CI] 1.75-5.13, P < 0.0001) than that of TACE and/or PRFA alone treatment. There was no significant difference between the combined therapy and monotherapy on 1-year recurrence-free survival rate ([OR] 1-year = 1.55, [95 % CI] 0.91-2.65, P = 0.11). CONCLUSIONS The data of our study indicate that the combination of TACE and PRFA has better effectiveness than that of TACE and PRFA monotherapy in the treatment for patients with HCC.
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Affiliation(s)
- Jia-yan Ni
- Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510210, People's Republic of China.
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Xu LF, Sun HL, Chen YT, Ni JY, Chen D, Luo JH, Zhou JX, Hu RM, Tan QY. Large primary hepatocellular carcinoma: transarterial chemoembolization monotherapy versus combined transarterial chemoembolization-percutaneous microwave coagulation therapy. J Gastroenterol Hepatol 2013; 28:456-63. [PMID: 23216261 DOI: 10.1111/jgh.12088] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/27/2012] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIM To evaluate the clinical benefits of transarterial chemoembolization (TACE) monotherapy or TACE combined with percutaneous microwave coagulation therapy (PMCT) and the long-term survival rate of patients with large primary hepatocellular carcinoma (HCC) treated with these techniques. METHODS This is a retrospective study involving 136 patients with unresectable large HCC (189 tumor nodules, ≥ 5.0 cm in diameter) admitted to Sun Yat-Sen University Memorial Hospital (Guangzhou, China) between January 2004 and December 2011. The median follow-up time was 41 months (range, 6-96 months). Of these patients, 80 patients received TACE monotherapy and 56 patients received TACE combined with PMCT. The median interval between treatments and overall survival (OS) were hierarchically analyzed using log-rank tests. RESULTS All patients successfully underwent TACE alone or TACE with PMCT with no serious complications. The median survival time was 13 months (range, 3-84 months) for the TACE group and 25 months (range, 7-96 months) for the TACE-PMCT group. The 1-year, 3-year, and 5-year OS rates were 62.5%, 17.5%, and 5.0% in the TACE group, respectively. In contrast, in the TACE-PMCT group, the 1-year, 3-year, and 5-year OS rates were 87.5%, 50.0%, and 10.0%, respectively. This difference was statistically significant between the groups (P < 0.001). CONCLUSIONS TACE combined with PMCT had advantages in prolonging OS with satisfying time to progression and improving liver function in patients with large unresectable HCC. The results suggest that further prospective studies are required to confirm the findings of this study.
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Affiliation(s)
- Lin-Feng Xu
- Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
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Nakasone Y, Kawanaka K, Ikeda O, Tamura Y, Yamashita Y. Sequential combination treatment (arterial embolization and percutaneous radiofrequency ablation) of inoperable renal cell carcinoma: single-center pilot study. Acta Radiol 2012; 53:410-4. [PMID: 22393159 DOI: 10.1258/ar.2012.110413] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
BACKGROUND Potential drawbacks of percutaneous radiofrequency ablation (RFA) for renal cell carcinoma (RCC) include local recurrence after RFA due to a limited ablation area, massive hemorrhage induced by kidney puncture, and difficulty in visualizing the tumor at CT-guided puncture. PURPOSE To evaluate retrospectively the technical success, effectiveness, and complications elicited in patients with unresectable RCC following single-session sequential combination treatment consisting of renal arterial embolization followed by RFA. MATERIAL AND METHODS Ten patients (12 RCCs) who were not candidates for surgery were included in this pilot study. All tumors ranged from 18-66 mm in size (mean 31 ± 3.9 mm), and were percutaneously ablated several hours after embolization of the tumor vessels with iodized oil and gelatin sponges. We evaluated the technical success, effectiveness, effect on renal function, and complications of this treatment. Effectiveness was judged on CT and/or MR images obtained every three months after RFA. The effect on renal function was assessed based on the creatinine level and glomerular filtration rate (GFR) before, one week, and three months after the procedure. RESULTS Renal arterial embolization followed by percutaneous RFA was technically successful in all patients. On contrast CT and/or MR images obtained one week and three months after RFA we observed necrosis in the embolized segment of all RCCs. There were no major complications during and after the procedure. All patients reported tolerable pain and a burning sensation during RFA. After the procedure, five patients (50%) experienced back pain, one each manifested fluid collection, subcapsular hematomas, hematuria, or nausea. There were no instances of recurrence during a mean follow-up period of 47 ± 3.8 months. We noted no significant difference in serum creatinine and GFR before and after treatment. CONCLUSION Our pilot study suggests that sequential combination treatment by renal arterial embolization followed by percutaneous RFA is feasible in patients with inoperable RCC. The treatment complications were acceptable and excellent effects were obtained.
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Affiliation(s)
- Yutaka Nakasone
- Department of Diagnostic Radiology, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Honjo Kumamoto, Japan
| | - Koichi Kawanaka
- Department of Diagnostic Radiology, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Honjo Kumamoto, Japan
| | - Osamu Ikeda
- Department of Diagnostic Radiology, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Honjo Kumamoto, Japan
| | - Yoshitaka Tamura
- Department of Diagnostic Radiology, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Honjo Kumamoto, Japan
| | - Yasuyuki Yamashita
- Department of Diagnostic Radiology, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Honjo Kumamoto, Japan
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Seong NJ, Yoon CJ, Kang SG, Chung JW, Kim HC, Park JH. Effects of arsenic trioxide on radiofrequency ablation of VX2 liver tumor: intraarterial versus intravenous administration. Korean J Radiol 2012; 13:195-201. [PMID: 22438687 PMCID: PMC3303903 DOI: 10.3348/kjr.2012.13.2.195] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2011] [Accepted: 08/24/2011] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE Arsenic trioxide (As(2)O(3)) can be used as a possible pharmaceutical alternative that augments radiofrequency (RF) ablation by reducing tumor blood flow. The aim of this study was to assess the effect of intraarterial and intravenous administration of As(2)O(3) on RF-induced ablation in an experimentally induced liver tumor. MATERIALS AND METHODS VX2 carcinoma was grown in the livers of 30 rabbits. As(2)O(3) (1 mg/kg) was administered through the hepatic artery (n = 10, group A) or ear vein (n = 10, group B), 30 minutes before RF ablation (125 mA ± 35; 90 ± 5℃). As a control group, 10 rabbits were treated with RF ablation alone (group C). RF was intentionally applied to the peripheral margin of the tumor so that ablation can cover the tumor and adjacent hepatic parenchyma. Ablation areas of the tumor and adjacent parenchymal changes among three groups were compared by the Kruskal-Wallis and Mann-Whitney U test. RESULTS The overall ablation areas were 156 ± 28.9 mm(2) (group A), 119 ± 31.7 (group B), and 92 ± 17.4 (group C, p < 0.04). The ablation area of the tumor was significantly larger in group A (73 ± 19.7 mm(2)) than both group B (50 ± 19.4, p = 0.02) and group C (28 ± 2.2, p < 0.01). The ratios of the tumoral ablation area to the overall ablation area were larger in group A (47 ± 10.5%) than that of the other groups (42 ± 7.3% in group B and 32 ± 5.6% in group C) (p < 0.03). CONCLUSION Radiofrequency-induced ablation area can be increased with intraarterial or intravenous administration of As(2)O(3). The intraarterial administration of As(2)O(3) seems to be helpful for the selective ablation of the tumor.
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Affiliation(s)
- Nak Jong Seong
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
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Smith MT, Ray CE. The treatment of primary and metastatic hepatic neoplasms using percutaneous cryotherapy. Semin Intervent Radiol 2011; 23:39-46. [PMID: 21326719 DOI: 10.1055/s-2006-939840] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Cryotherapy has been used clinically in the treatment of metastatic liver malignancies since the 1980s. Rapid freezing to sub-zero temperatures promotes ice formation in the extracellular space and the exit of intracellular water. Cellular death is the result of dehydration, protein denaturation, and microcirculatory failure. Cryotherapy probes use nitrogen or argon gas as a coolant and the development of the ice ball can be monitored using ultrasound, computed tomography, or magnetic resonance imaging. Traditionally, cryotherapy has been performed during laparoscopy or laparotomy, using intraoperative ultrasound for image guidance. A decrease in cryoprobe size (from ~24 Fr to ~15 gauge) in conjunction with experience gained in open cryosurgical treatment has allowed the development of minimally invasive percutaneous approaches. In this review, we describe the use of cryotherapy for treatment of primary or secondary liver neoplasms using a percutaneous approach.
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Affiliation(s)
- Mitchell T Smith
- Department of Radiology, University of Colorado Health Sciences Center, Denver, Colorado
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Morimoto M, Numata K, Kondou M, Nozaki A, Morita S, Tanaka K. Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma. Cancer 2010; 116:5452-60. [DOI: 10.1002/cncr.25314] [Citation(s) in RCA: 239] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2009] [Revised: 01/07/2010] [Accepted: 01/28/2010] [Indexed: 02/06/2023]
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Arii S, Sata M, Sakamoto M, Shimada M, Kumada T, Shiina S, Yamashita T, Kokudo N, Tanaka M, Takayama T, Kudo M. Management of hepatocellular carcinoma: Report of Consensus Meeting in the 45th Annual Meeting of the Japan Society of Hepatology (2009). Hepatol Res 2010; 40:667-85. [PMID: 20633193 DOI: 10.1111/j.1872-034x.2010.00673.x] [Citation(s) in RCA: 134] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is responsible for approximately 600 000-700 000 deaths worldwide. It is highly prevalent in the Asia-Pacific region and Africa, and is increasing in Western countries. The evidence-based guideline for HCC in Japan was published in 2005 and revised in 2009. Apart from this guideline, a consensus-based practice manual proposed by the HCC expert panel of the Japan Society of Hepatology (JSH), which reflects widely accepted daily practice in Japan, was published in 2007. At the occasion of the 45th Annual meeting of the JSH in Kobe 4-5 June 2009, a consensus meeting of HCC was held. Consensus statements were createdbased on 67% agreement of 200 expert members.This article describes the up-to-date consensus statements which largely reflect the real world HCC practice in Japan. We believe readers of this article will gain the newest knowledge and deep insight on the management of HCC proposed by consensus of the HCC expert members of JSH.
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Affiliation(s)
- Shigeki Arii
- Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University Graduate School of Medicine
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Barakat O, Wood RP, Ozaki CF, Ankoma-Sey V, Galati J, Skolkin M, Toombs B, Round M, Moore W, Mieles L. Morphological features of advanced hepatocellular carcinoma as a predictor of downstaging and liver transplantation: an intention-to-treat analysis. Liver Transpl 2010; 16:289-99. [PMID: 20209588 DOI: 10.1002/lt.21994] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
In selected patients, locoregional therapy (LRT) has been successful in downstaging advanced hepatocellular carcinoma (HCC) so that the conventional criteria for liver transplantation (LT) can be met. However, the factors that predict successful treatment are largely unidentified. To determine these factors, we analyzed our experience with multimodal LRT in downstaging advanced HCC before LT in a retrospective cohort study. Thirty-two patients with advanced HCC exceeding conventional and expanded criteria for LT underwent therapy, but only those patients whose tumors were successfully downstaged were considered for LT. Eighteen patients (56%) had their tumors successfully downstaged; 14 patients (44%) did not. No intergroup differences existed with respect to patient characteristics or the types and number of treatments. However, mean alpha-fetoprotein levels were significantly higher in the non-downstaged group than in the downstaged group (P < 0.048), and significantly more patients in the non-downstaged group had infiltrative tumors (P = 0.0001). The median survival time was 42 and 7 months for the downstaged and non-downstaged groups, respectively (P = 0.0006). Fourteen patients (43.3%) underwent LT. After a median follow-up period of 35 months (range, 1.5-50 months) after LT, 2 patients (14.2%) developed tumor recurrence. The Kaplan-Meier survival rates after LT were 92% at 1 year and 75% at 2 years. The noninfiltrative expanding tumor type was the sole predictor of successful downstaging and improved outcome on univariate and multivariate analyses. Our study suggests that, in patients with advanced HCC, morphological characteristics of the tumor may predict a good response to downstaging and an improved outcome after LT.
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Affiliation(s)
- Omar Barakat
- Department of Hepatobiliary and Liver Transplant Surgery, St. Luke's Episcopal Hospital, 6624 Fannin, Houston, TX 77030, USA.
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Yu Y, Lang Q, Chen Z, Li B, Yu C, Zhu D, Zhai X, Ling C. The efficacy for unresectable hepatocellular carcinoma may be improved by transcatheter arterial chemoembolization in combination with a traditional Chinese herbal medicine formula: a retrospective study. Cancer 2009; 115:5132-8. [PMID: 19672999 DOI: 10.1002/cncr.24567] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Transcatheter arterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) because of its survival benefit, although its clinical effect is still far from satisfactory. In China, there has been a long history of using traditional Chinese medicine in the treatment of liver cancer and other malignancies. In this study, the authors evaluated the effect of combined therapy with TACE and JDF granule preparation (a traditional Chinese herbal medicine formula) in the treatment of patients with unresectable HCC on survival. Clinical data, including baseline, performance status change, and survival time of 165 patients with unresectable HCC seen between January 2002 and December 2007 were retrospectively analyzed. Among the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and 85 patients (control group) received TACE alone. The survival rate of both groups was calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model. The median overall survival was 9.2 months (95% confidence interval [95% CI], 6.94-1.46) in the study group versus 5.87 months (95% CI, 4.21-7.52) in the control group. In the study group (TACE + JDF), 1-year, 2-year, and 3-year survival rates were 41.2%, 18.4%, and 9.6%, respectively. The Cox regression analysis revealed the therapy model to be an independent predictor of patient prognosis. Current study data demonstrated that TACE combined with JDF granule preparation could improve the prognosis of patients. TACE combined with JDF granule preparation may prolong survival of patients with unresectable HCC.
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Affiliation(s)
- Yang Yu
- Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China
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25
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Yang W, Chen MH, Wang MQ, Cui M, Gao W, Wu W, Wu JY, Dai Y, Yan K. Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment. Hepatol Res 2009; 39:231-40. [PMID: 19054154 DOI: 10.1111/j.1872-034x.2008.00451.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM To assess the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) in recurrent hepatocellular carcinoma (HCC) after hepatectomy and to compare its outcome with a single modality. METHOD We retrospectively studied 103 patients with recurrent HCCs after hepatectomy who were excluded from repeat hepatectomy. Of them, 81 patients were male and 22 were female (mean age 55.8 +/- 10.7 years; range, 30-80 years). According to treatment modality, these patients were divided into three groups: RFA was used as the sole first-line anticancer treatment in 37 patients (RFA group); TACE was used as the sole first-line anticancer treatment in 35 patients (TACE group). RFA followed by TACE was performed in 31 patients (combination group). There was no significant difference in clinical material between the three groups. Indices including treatment success rate, intrahepatic recurrence rate and survival were obtained for analysis and comparison. RESULTS The treatment success rate of the combination group was significantly higher than that of the TACE group (93.5 vs. 68.6%, P = 0.011). The intrahepatic recurrence rate of the combination group was significantly lower than that of the TACE group (20.7 vs 57.1%, P = 0.002) and the RFA group (20.7 vs 43.2%, P = 0.036). The overall 1-, 3- and 5-year survival rates were 73.9, 51.1 and 28.0% respectively in the RFA group; 65.8, 38.9 and 19.5% respectively in the TACE group; and 88.5, 64.6 and 44.3% respectively in the combination group. There was a significant difference in survival between the combination group and the TACE group (P = 0.028). CONCLUSION RFA combined with TACE was more effective in treating recurrent HCC after hepatectomy compared to single RFA or TACE treatment. This combination therapy can thus be a valuable choice of treatment for recurrent HCC.
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Affiliation(s)
- Wei Yang
- Ultrasound Department, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China
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Pleguezuelo M, Marelli L, Misseri M, Germani G, Calvaruso V, Xiruochakis E, Manousou P, Burroughs AK. TACE versus TAE as therapy for hepatocellular carcinoma. Expert Rev Anticancer Ther 2009; 8:1623-41. [PMID: 18925854 DOI: 10.1586/14737140.8.10.1623] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Transarterial chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, best anticancer agent and best technique are still unclear. TACE may not be better than transarterial embolization (TAE). HCC is very chemoresistant, thus embolization may be more important than chemotherapy. Lipiodol cannot be considered as an embolic agent and there are no data to show that it can release chemotherapeutic agents slowly. It can mask residual vascularity on CT imaging and its use is not recommended. Both TACE and TAE result in hypoxia, which stimulates angiogenesis, promoting tumor growth; thus combination of TACE with antiangiogenic agents may improve current results. To date, there is no evidence that TACE pre-liver transplantation or resection helps to expand current selection criteria for patients with HCC, nor results in less recurrence after surgery. Combination with other techniques, such as radiofrequency ablation and drugs, may enhance the effect of TACE. New trials are being conducted to clarify these issues.
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Affiliation(s)
- Maria Pleguezuelo
- Department of Surgery & Liver Transplantation, The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, Hampstead Heath, London, UK.
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Takaki H, Yamakado K, Uraki J, Nakatsuka A, Fuke H, Yamamoto N, Shiraki K, Yamada T, Takeda K. Radiofrequency ablation combined with chemoembolization for the treatment of hepatocellular carcinomas larger than 5 cm. J Vasc Interv Radiol 2008; 20:217-24. [PMID: 19097810 DOI: 10.1016/j.jvir.2008.10.019] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2008] [Revised: 10/21/2008] [Accepted: 10/21/2008] [Indexed: 12/11/2022] Open
Abstract
PURPOSE To evaluate survival, recurrence-free survival, technical success, technique effectiveness, and safety of radiofrequency (RF) ablation combined with chemoembolization in patients with hepatocellular carcinomas (HCCs) larger than 5 cm. MATERIALS AND METHODS Patients with Child-Pugh class A or B cirrhosis and three or fewer HCCs with a maximum tumor diameter of 5.1-10 cm were included. Twenty patients with 32 HCCs were included. There were 16 men and four women with mean age of 69 years +/- 7.4 (range, 46-79 years).The maximum mean tumor diameter was 6.2 cm (range, 5.1-9.5 cm). RF ablation was performed under computed tomographic (CT) fluoroscopic guidance 1-2 weeks after chemoembolization. The primary endpoint of this study was survival. RESULTS RF electrodes were placed in the planned sites, and RF ablation was completed with a planned protocol (technical success rate, 100%). Tumor enhancement was eradicated in all patients after 32 RF sessions. The primary and secondary technique effectiveness rates were 40% and 100%, respectively. There were two major complications in the 32 RF sessions (6%)--hepatic abscess and diaphragm perforation. Local tumor progression developed in five of the 20 patients (25%) during the mean follow-up of 30 months. The overall and recurrence-free survival rates were, respectively, 100% and 74% at 1 year, 62% and 28% at 3 years, and 41% and 14% at 5 years. The serum bilirubin level of 1.0 mg/dL (17.1 micromol/L) or less was a significantly better prognostic factor in the univariate analysis. CONCLUSIONS This combination therapy may enhance survival in patients with HCCs larger than 5 cm.
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Affiliation(s)
- Haruyuki Takaki
- Department of Radiology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
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Li SQ, Ni CF, Jiang GM, Chen L. Combined therapy of radiofrequency ablation with transcatheter artery embolization in rabbit model of hepatic carcinoma. Shijie Huaren Xiaohua Zazhi 2008; 16:3677-3680. [DOI: 10.11569/wcjd.v16.i32.3677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the safety about the combined therapy of radiofrequency ablation (RFA) with transcatheter artery embolization (TAE) in rabbits with VX2 hepatic carcinoma.
METHODS: VX2 tumor tissues were implanted into the rabbit's liver to establish liver cancer model. Thirty-six rabbits with hepatic carcinoma were assigned to 4 groups randomly (n = 9). Group A received RFA treatment only; group B, C, D received TAE treatment 1, 4, 7 d prior to RFA treatment respectively. The ALT and UREA levels of the experimental rabbits were measured before and after each treatment.
RESULTS: Decreased appetite, drowsiness and dispiritedness were observed in the rabbits, especially in group B and C. No death was observed in group A and group D, but there were 3 deaths in group B and 2 deaths in group C. ALT levels were the highest at the first day in all groups. The difference was significant at the first day between group B (385.0 ± 213.1 U/L), C (289.2 ± 192.6 U/L) and A (178.4 ± 49.2 U/L), D (208.2 ± 65.5 U/L) respectively (P < 0.05), but not significant between group B and C, group A and D; There were no differences between each group at the 4th day and 7th day. No statistical significance in UREA levels was observed among the four groups.
CONCLUSION: RFA at 1, 4 d after TAE might impact liver function severely. RFA, is relatively safe at 7 d after TAE treatment. Combined therapy of RFA and TAE exerts no impact on renal function in all groups.
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Murakami T, Ishimaru H, Sakamoto I, Uetani M, Matsuoka Y, Daikoku M, Honda S, Koshiishi T, Fujimoto T. Percutaneous radiofrequency ablation and transcatheter arterial chemoembolization for hypervascular hepatocellular carcinoma: rate and risk factors for local recurrence. Cardiovasc Intervent Radiol 2007; 30:696-704. [PMID: 17497071 DOI: 10.1007/s00270-007-9003-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE To analyze local recurrence-free rates and risk factors for recurrence following percutaneous radiofrequency ablation (RFA) or transcatheter arterial chemoembolization (TACE) for hypervascular hepatocellular carcinoma (HCC). METHODS One hundred and nine nodules treated by RFA and 173 nodules treated by TACE were included. Hypovascular nodules were excluded from this study. Overall local recurrence-free rates of each treatment group were calculated using the Kaplan-Meier method. The independent risk factors of local recurrence and the hazard ratios were analyzed using Cox's proportional-hazards regression model. Based on the results of multivariate analyses, we classified HCC nodules into four subgroups: central nodules < or =2 cm or >2 cm and peripheral nodules < or =2 cm or >2 cm. The local recurrence-free rates of these subgroups for each treatment were also calculated. RESULTS The overall local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p = 0.013). The 24-month local recurrence-free rates in the RFA and TACE groups were 60.0% and 48.9%, respectively. In the RFA group, the only significant risk factor for recurrence was tumor size >2 cm in greatest dimension. In the TACE group, a central location was the only significant risk factor for recurrence. In central nodules that were < or =2 cm, the local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p < 0.001). In the remaining three groups, there was no significant difference in local recurrence-free rate between the two treatment methods. CONCLUSION A tumor diameter of >2 cm was the only independent risk factor for local recurrence in RFA treatment, and a central location was the only independent risk factor in TACE treatment. Central lesions measuring < or =2 cm should be treated by RFA.
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MESH Headings
- Adult
- Aged
- Angiography
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Carcinoma, Hepatocellular/blood supply
- Carcinoma, Hepatocellular/diagnostic imaging
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/surgery
- Chemoembolization, Therapeutic/methods
- Disease-Free Survival
- Electrocoagulation/methods
- Epirubicin/administration & dosage
- Follow-Up Studies
- Humans
- Liver Neoplasms/blood supply
- Liver Neoplasms/diagnostic imaging
- Liver Neoplasms/drug therapy
- Liver Neoplasms/surgery
- Male
- Middle Aged
- Mitomycin/administration & dosage
- Neoplasm Recurrence, Local/diagnostic imaging
- Neoplasm Recurrence, Local/etiology
- Neoplasms, Multiple Primary/blood supply
- Neoplasms, Multiple Primary/diagnostic imaging
- Neoplasms, Multiple Primary/drug therapy
- Neoplasms, Multiple Primary/radiotherapy
- Neovascularization, Pathologic/diagnostic imaging
- Neovascularization, Pathologic/drug therapy
- Neovascularization, Pathologic/surgery
- Retrospective Studies
- Risk Factors
- Tomography, X-Ray Computed
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Affiliation(s)
- Tomonori Murakami
- Department of Radiology, National Nagasaki Medical Center, 2-1001-1 Kubara, Omura, 856-8562, Japan.
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Kurokohchi K, Deguchi A, Masaki T, Himoto T, Yoneyama H, Kobayashi M, Maeta T, Kiuchi T, Kohi F, Miyoshi H, Taminato T, Kuriyama S. Successful treatment of hypovascular advanced hepatocellular carcinoma with lipiodol-targetting intervention radiology. World J Gastroenterol 2007; 13:4398-400. [PMID: 17708619 PMCID: PMC4250872 DOI: 10.3748/wjg.v13.i32.4398] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We report a case of hypovascular advanced hepa-tocellular carcinoma (HCC) successfully treated with a novel combination therapy of percutaneous ethanol-lipiodol injection (PELI) and intervention radiology (IVR), lipiodol-targetting IVR (Lipi-IVR). The present case had a hypovascular HCC (3 cm in diameter) located in the S6 region of the liver. Although the tumor was not detectable at all by both of early and late phase of helical dynamic computed tomography (CT), it could be detected by ultrasonography (US) as a low echoic space occupying lesion (SOL) beside the gallbladder and right kidney. Serum levels of alpha fetoprotein (AFP) and AFP-L3 were extremely high. Combination therapy of PELI, firstly reported in our department, and IVR (PELI and IVR, lipiodol-targetting IVR) was performed twice for the treatment. PELI could effectively visualize the location of the tumor for IVR treatment and show the presence of a thin blood vessel branching from the right hepatic artery flowing into the lipiodol deposit. After treatment, the serum levels of AFP and AFP-L3 were rapidly decreased to normal and maintained for more than eight months. Thus, this case expressing the tremendous effect might give us insight into the effectiveness of the novel combination therapy of PELI and IVR for the treatment of hypovascular HCC.
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Affiliation(s)
- Kazutaka Kurokohchi
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
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31
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Zhang YJ, Liang HH, Chen MS, Guo RP, Li JQ, Zheng Y, Zhang YQ, Lau WY. Hepatocellular Carcinoma Treated with Radiofrequency Ablation with or without Ethanol Injection: A Prospective Randomized Trial. Radiology 2007; 244:599-607. [PMID: 17641378 DOI: 10.1148/radiol.2442060826] [Citation(s) in RCA: 110] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE To prospectively evaluate whether use of combined radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) results in better survival compared with use of RFA alone in patients with hepatocellular carcinoma. MATERIALS AND METHODS This study was local ethical committee approved; all patients gave written informed consent. One hundred thirty-three patients were randomly assigned to undergo RFA-PEI (n = 66; 57 men, nine women; mean age, 53.3 years; age range, 32-73 years) or RFA alone (n = 67; 58 men, nine women; mean age, 52.2 years; age range, 33-74 years). Patients with viable tumors at computed tomography (CT) 4 weeks after treatment received additional treatment. Overall survival rates were calculated and 3-year survival rates were compared with life-table and Mantel-Haenszel analyses, respectively. Survival curves were constructed and compared by using Kaplan-Meier and log-rank tests, respectively. The relative prognostic significance of variables in predicting overall survival and the time to tumor recurrence or metastasis were assessed with multivariate Cox proportional hazards regression and logistic regression analyses, respectively. RESULTS One-, 2-, 3-, 4-, and 5-year overall survival rates were 95.4%, 89.2%, 75.8%, 63.3%, and 49.3%, respectively, with RFA-PEI and 89.6%, 68.7%, 58.4%, 50.3%, and 35.9%, respectively, with RFA alone. The survival curve for the RFA-PEI group was significantly better than that for the RFA-only group (P = .04). The survival curve for the RFA-PEI group was better than that for the RFA-only group with 3.1-5.0-cm tumors (P = .03) but not for those with 3.0 cm or smaller (P = .44) or 5.1-7.0-cm (P = .70) tumors. Overall tumor recurrence was lower with RFA-PEI (23 patients) than with RFA alone (33 patients, nonsignificant difference). Local recurrence was significantly lower with RFA-PEI (four patients) than with RFA alone (14 patients, P = .012). Tumor diameter proved to be the only significant prognostic factor for overall recurrence and intrahepatic recurrence. Treatment type and tumor size were significant prognostic factors for local recurrence. CONCLUSION RFA-PEI facilitated better local tumor control and long-term survival compared with RFA alone.
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Affiliation(s)
- Yao-Jun Zhang
- Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-Sen University, 651 Dongfeng Rd East, Guangzhou 510060, China
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Liu Z, Ahmed M, Sabir A, Humphries S, Goldberg SN. Computer modeling of the effect of perfusion on heating patterns in radiofrequency tumor ablation. Int J Hyperthermia 2007; 23:49-58. [PMID: 17575723 DOI: 10.1080/02656730601094415] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
PURPOSE To use an established computer simulation model of radiofrequency (RF) ablation to further characterize the effect of varied perfusion on RF heating for commonly used RF durations and electrode types, and different tumor sizes. METHODS Computer simulation of RF heating using 2-D and 3-D finite element analysis (Etherm) was performed. Simulated RF application was systematically modeled on clinically relevant application parameters for a range of inner tumor perfusion (0-5 kg/m3-s) and outer normal surrounding tissue perfusion (0-5 kg/m3-s) for internally cooled 3-cm single and 2.5-cm cluster electrodes over a range of tumor diameters (2-5 cm), and RF application times (5-60 min; n = 4618 simulations). Tissue heating patterns and the time required to heat the entire tumor +/- a 5-mm margin to > 50 degrees C were assessed. Three-dimensional surface response contours were generated, and linear and higher order curve-fitting was performed. RESULTS For both electrodes, increasing overall tissue perfusion exponentially decreased the overall distance of the 50 degrees C isotherm (R2 = 0.94). Simultaneously, increasing overall perfusion exponentially decreased the time required to achieve thermal equilibrium (R2 = 0.94). Furthermore, the relative effect of inner and outer perfusion varied with increasing tumor size. For smaller tumors (2 cm diameter, 3-cm single; 2-3 cm diameter, cluster), the ability and time to achieve tumor ablation was largely determined by the outer tissue perfusion value. However, for larger tumors (4-5 cm diameter single; 5 cm diameter cluster), inner tumor perfusion had the predominant effect. CONCLUSION Computer modeling demonstrates that perfusion reduces both RF coagulation and the time to achieve thermal equilibrium. These results further show the importance of considering not only tumor perfusion, but also size (in addition to background tissue perfusion) when attempting to predict the effect of perfusion on RF heating and ablation times.
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Affiliation(s)
- Z Liu
- Department of Radiology, Beth Israel Deaconess Medical Center-Harvard Medical School, Boston, MA 02215, USA
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Nakai M, Sato M, Sahara S, Kawai N, Tanihata H, Kimura M, Terada M. Radiofrequency ablation in a porcine liver model: Effects of transcatheter arterial embolization with iodized oil on ablation time, maximum output, and coagulation diameter as well as angiographic characteristics. World J Gastroenterol 2007; 13:2841-5. [PMID: 17569120 PMCID: PMC4395636 DOI: 10.3748/wjg.v13.i20.2841] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effects of combined radiofrequency ablation and transcatheter arterial embolization with iodized oil on ablation time, maximum output, coagulation diameter, and portal angiography in a porcine liver model.
METHODS: Radiofrequency ablation (RFA) was applied to in vivo livers of 10 normal pigs using a 17-gauge 3.0 cm expandable LeVeen RF needle electrode with or without transcatheter arterial embolization (TAE) with iodized oil (n = 5). In each animal, 2 areas in the liver were ablated. Direct portography was performed before and after RFA. Ablation was initiated at an output of 30 W, and continued with an increase of 10 W per minute until roll-off occurred. Ablation time and maximum output until roll-off, and coagulated tissue diameter were compared between the 2 groups. Angiographic changes on portography before and after ablation were also reviewed.
RESULTS: For groups with and without TAE with iodized oil, the ablation times until roll-off were 320.6 ± 30.9 seconds and 445.1 ± 35.9 seconds, respectively, maximum outputs were 69.0 ± 7.38 W and 87.0 ± 4.83 W and maximal diameters of coagulation were 41.7 ± 3.85 mm and 33.2 ± 2.28 mm. Significant reductions of ablation time and maximum output, and significantly larger coagulation diameter were obtained with RFA following TAE with iodized oil compared to RFA alone. Portography after RFA following TAE with iodized oil revealed more occlusion of the larger portal branches than with RFA alone.
CONCLUSION: RFA following TAE with iodized oil can increase the volume of coagulation necrosis with lower output and shorter ablation time than RFA alone in normal pig liver tissue.
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Affiliation(s)
- Motoki Nakai
- Department of Radiology, Hidaka General Hospital, 116-2 Sono, Gobo Shi, Wakayama 644-8655, Japan.
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Liao GS, Yu CY, Shih ML, Chan DC, Liu YC, Yu JC, Chen TW, Hsieh CB. Radiofrequency ablation after transarterial embolization as therapy for patients with unresectable hepatocellular carcinoma. Eur J Surg Oncol 2007; 34:61-6. [PMID: 17434711 DOI: 10.1016/j.ejso.2007.02.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2006] [Accepted: 02/09/2007] [Indexed: 10/23/2022] Open
Abstract
PURPOSE To evaluate the usefulness of transcatheter arterial embolization (TAE) followed by radiofrequency ablation (RFA) as combined treatment for unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS Thirty-six consecutive patients (cirrhosis, Child-Pugh class A or B) with solitary or oligonodular HCC were treated (41 lesions; mean size, 58.9 mm; range, 30-120 mm). RFA was performed after one TAE treatment. Local efficacy was evaluated with multiphasic computed tomography (CT) performed an average of two months after RFA and once during later follow-up. RESULTS The mean follow-up period was 16 months (range, 2-45 months). Technical success (namely, complete tumor devascularization during the arterial phase) was achieved for 59% of lesions at the first CT evaluation and for 46% at the second evaluation. Among prognostic factors included in the analysis, only lesion diameter (< 50 mm versus > or = 50 mm) was statistically significant in terms of predicting local success (Fisher's exact test: 85% versus 43% at first CT, p<0.01; 70% versus 36% during follow-up, p=0.05). There were no major periprocedural complications. Kaplan-Meier analysis showed survival rates of 84% at 12 months and 57% at 24 months. CONCLUSIONS Combined therapy--TAE then RFA--for unresectable HCC lesions in patients with cirrhosis produces a relatively high complete local response rate compared with TAE or RFA alone. Our results, considered with those from other case series, may help design prospective, randomized clinical trials to test combination therapy versus single-modality therapy in terms of risks and benefits.
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Affiliation(s)
- G S Liao
- Department of Surgery, Penghu Branch, Tri-Service General Hospital, No. 90, Cianliao Village, Magong City 880, Penghu County, Taiwan
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Gebauer B, Werk M, Lopez-Hänninen E, Felix R, Althaus P. Radiofrequency Ablation in Combination with Embolization in Metachronous Recurrent Renal Cancer in Solitary Kidney after Contralateral Tumor Nephrectomy. Cardiovasc Intervent Radiol 2007; 30:644-9. [PMID: 17436034 DOI: 10.1007/s00270-007-9012-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
PURPOSE To evaluate the feasibility and safety of minimally invasive, percutaneous techniques in metachronous recurrent renal cell cancers (RCCs) in solitary kidneys. METHODS In 4 patients, recurrent RCC was treated by radiofrequency ablation (RFA) (RITA, StarBurst) alone, and in 2 patients by RFA in combination with superselective transarterial particle-lipiodol embolization using 3 Fr microcatheters. RFA was guided by computed tomography in 5 patients, and by magnetic resonance imaging in 1 patient. Mean tumor diameter was 26.7 mm (range 10-45 mm). All interventions were technically successful; during follow-up 1 patient developed recurrent RCC, which was retreated by RFA after embolization. RESULTS No major peri- or postprocedural complications occurred. Changes in creatinine (pre- vs. post-intervention, 122 vs. 127 micromol/l) and calculated creatinine clearance (pre- vs. post-intervention, 78 vs. 73 ml/min) after ablation were minimal. CONCLUSION In single kidneys, percutaneous, minimally invasive techniques are safe and feasible. In large tumors, or where there are adjacent critical structures, we prefer a combination of embolization and thermal ablation (RFA).
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Affiliation(s)
- Bernhard Gebauer
- Department of Radiology, Charité, Universitätsmedizin Berlin Campus Virchow-Clinic, Augustenburger Platz 1, 13353, Berlin, Germany.
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Wang YB, Chen MH, Yan K, Yang W, Dai Y, Yin SS. Quality of life after radiofrequency ablation combined with transcatheter arterial chemoembolization for hepatocellular carcinoma: comparison with transcatheter arterial chemoembolization alone. Qual Life Res 2007; 16:389-97. [PMID: 17111232 DOI: 10.1007/s11136-006-9133-9] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2005] [Accepted: 09/22/2006] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Comprehensive studies are scarce with regard to the quality of life (QOL) of hepatocellular carcinoma (HCC) patients after transcatheter arterial chemoembolization (TACE) and/or radiofrequency ablation (RFA) treatment. The purpose of this study was to examine the impact of TACE alone and that of the TACE followed by RFA (TACE-RFA) on QOL in HCC patients. METHODS QOL was measured using the Functional Assessment of Cancer Therapy-General (FACT-G) (Version 4.0) questionnaire, translated into Chinese, as a measure of QOL among Chinese HCC patients. Prospectively, 83 patients in both TACE group (n = 40) and TACE-RFA group (n = 43) completed the questionnaire at baseline and 3 months after treatment, respectively. RESULTS The TACE-RFA group resulted in a significantly higher total QOL score, socio-family well-being score, and functional well-being score than that of TACE group, 3 months after respective treatment. Liver function, tumor recurrence and complication, age, income were the most important factors affecting the QOL of HCC patients after treatment. The logistic regression analyses showed that Child-Pugh Class and tumor recurrence after treatment were independent predictors of post-treatment QOL scores of HCC patients. CONCLUSIONS The overall QOL of HCC patients in TACE-RFA group was maintained at a relatively higher level than that of TACE group. TACE followed by RFA appeared to be more favorable than TACE alone with respect to QOL.
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Affiliation(s)
- Yan-Bin Wang
- Department of Ultrasound, Clinical Oncology Institute, Beijing University, No. 52 Fu-cheng Road, Hai-dian District, Beijing, 100036, China.
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Shinomiya H, Shibata H, Tamaki K, Fukuno H, Tsutsui A, Shimizu I, Ito S. Historical changes of hospitalization in patients with hepatocellular carcinoma considering for clinical path preparation. THE JOURNAL OF MEDICAL INVESTIGATION 2007; 54:124-32. [PMID: 17380023 DOI: 10.2152/jmi.54.124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
We examined the hospitalization time in 346 patients with hepatocellular carcinoma who were treated between January 1991 and March 2002 (486 admissions). A newly introduced IVR CT system and an advanced catheter shortened the mean time from 65.0 (1991) to 35.6 (2001) days in patients who underwent transcatheter arterial embolization (TAE). For patients having TAE combined with percutaneous ethanol infusion (PEI), the mean time was shortened from 156.5 to 48.7 days. In those who underwent PEI, the values were 56.0 and 36.8 days, respectively. In those who underwent radio frequency ablation (RFA), the mean time in 2001 was 25.3 days. Overall, the mean time was shortened from 60.5 to 38.0 days. In particular, the mean time (41.0 days) after 1999, when the IVR CT system and RFA were introduced, was significantly shorter than that before their introduction (58.9 days). Advances in instruments and procedures for TAE have greatly shortened the hospitalization period. In patients who underwent PEI, the rate of decrease in the mean time was small and it is difficult decrease their length of hospital stay; therefore, RFA may be frequently employed in the future.
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Affiliation(s)
- Hirohiko Shinomiya
- Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
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Kudo K, Moriyasu F, Mine Y, Miyata Y, Sugimoto K, Metoki R, Kamamoto H, Suzuki S, Shimizu M, Miyahara T, Yokoi M, Horibe T, Yamagata H. Preoperative RFA simulation for liver cancer using a CT virtual ultrasound system. Eur J Radiol 2007; 61:324-31. [PMID: 17049791 DOI: 10.1016/j.ejrad.2006.09.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2006] [Revised: 07/11/2006] [Accepted: 09/11/2006] [Indexed: 10/24/2022]
Abstract
We developed a computed tomography (CT) virtual ultrasound system (CVUS) as an imaging system to support treatment under percutaneous ultrasound (US) guidance. This prototype clinical system, produced in collaboration with Tokyo Medical University, uses display software developed by Toshiba Medical Systems. We examined the utility of this system by scheduling treatment plans preoperatively and simulating puncture and radiofrequency ablation (RFA) for liver cancer. The study enrolled 51 liver cancer patients with 66 nodules 0.8-8cm in diameter in which RFA was performed between June 2004 and December 2004. Virtual US and multiplanar reconstruction (MPR) images were constructed on the basis of DICOM CT data and puncture and ablation of liver cancer were simulated. The following were evaluated: (1) how to avoid complications and determine an appropriate puncture route by simulating puncture with C-mode MPR images; (2) determination of the three-dimensional location of the tumor for ablation, as well as the adjacent organs and vessels, by MPR rotation 360 degrees around the center of the tumor (center lock); and (3) how to determine the center and volume of ablation and avoid injuries to nearby organs and vessels by simulating ablation procedures. C -mode MPR images were effective for (1) determining and modifying the puncture route in 35 of 51 cases (69.6%) and (2) determining the spatial location of vessels and nearby organs in 50 of 51 cases (98.0%) by the center lock; and (3) simulating the ablation helped determine the center and volume of ablation by avoiding injuries to vessels and nearby organs in 45 or 51 cases (88.2%). Taken together, the CVUS allowed easy simulation of local treatment of liver cancer under US guidance using CT data alone and the preoperative simulation predicted an improvement in the safety of local therapy of liver cancer.
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Affiliation(s)
- Kosei Kudo
- Fourth Department of Gastroenterology and Hepatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjukuku-ku, Tokyo 160-0023, Japan
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Vallone P, Catalano O, Izzo F, Siani A. Combined ethanol injection therapy and radiofrequency ablation therapy in percutaneous treatment of hepatocellular carcinoma larger than 4 cm. Cardiovasc Intervent Radiol 2006; 29:544-51. [PMID: 16528626 DOI: 10.1007/s00270-005-0173-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND Optimal treatment of large-sized hepatocellular carcinoma (HCC) is still debated, because percutaneous ablation therapies alone do not always achieve complete necrosis. OBJECTIVE To report our experience in the treatment of patients with HCC larger than 4 cm in diameter by combined percutaneous ethanol injection and radiofrequency thermal ablation. METHODS In a 5-year period there were 40 consecutive patients meeting the inclusion criteria (24 men and 16 women; age range 41-72 years, mean 58 years). These subjects had a single HCC larger than 4 cm. Twelve subjects also had one or two additional nodules smaller than 4 cm (mean 1.2 nodules per patient). Patients were submitted to one to three sessions consisting of ethanol injection at two opposite tumor poles (mean 12 ml) and then of radiofrequency application through one or two electrodes placed at the tumor center (mean treatment duration 30 min). RESULTS Complete necrosis was obtained in all cases with one to three sessions (mean 1.3 sessions per patient). All patients experienced pain and fever but one only subject had a major complication requiring treatment (abscess development and fistulization). Overall follow-up was 7-69 months. Two patients showed local recurrence and 9 developed new etherotopic HCC nodules. Seven subjects died during follow-up while 33 were free from recurrence 8-69 months after treatment. CONCLUSION A combination of ethanol injection and radiofrequency ablation is effective in the treatment of large HCC.
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Affiliation(s)
- Paolo Vallone
- Department of Radiology, National Cancer Institute, Fondazione Pascale, via Semmola, 80131 Naples, Italy
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Marelli L, Stigliano R, Triantos C, Senzolo M, Cholongitas E, Davies N, Yu D, Meyer T, Patch DW, Burroughs AK. Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. Cancer Treat Rev 2006; 32:594-606. [PMID: 17045407 DOI: 10.1016/j.ctrv.2006.08.002] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2006] [Accepted: 08/20/2006] [Indexed: 12/30/2022]
Abstract
BACKGROUND Although transarterial chemoembolization (TACE) improves survival in patients with hepatocellular carcinoma (HCC), it is not known if TACE combined with other treatments is beneficial. AIM To evaluate the evidence for improved outcomes in HCC with a multimodal treatment approach involving TACE. METHOD PubMed search for all cohort and randomized trials (n=84) evaluating TACE combined with other therapies; meta-analysis performed where appropriate. RESULTS A meta-analysis involving 4 RCTs showed a significant decrease in mortality favouring combination treatment (TACE plus percutaneous ablation) compared to monotherapy in patients with either small (<3cm) or large HCC nodules (>3cm) (OR, 0.534; 95% CI, 0.288-0.990; p=0.046). TACE combined with local radiotherapy improved survival in patients with tumour thrombosis of the portal vein in 7 non-randomized studies. Two RCTs and 13 non-randomized studies showed that TACE prior to hepatic resection does not improve survival nor tumour recurrence. Conversely, 2 RCTs and 5 comparative studies showed that transarterial injection of chemotherapeutic drugs mixed with lipiodol (TOCE) following hepatectomy confers survival benefit and less tumour recurrence. TACE before liver transplantation is safe and reduces drop-out rate from the waiting list, but there is no current evidence of improvement in subsequent survival or recurrence rate. CONCLUSIONS A combined approach involving TACE and percutaneous ablation improves survival. Adjuvant TOCE improves outcome after hepatectomy. TACE is useful to control tumours burden while on the waiting list for OLT. Multimodal treatment seems to be the best way to optimize TACE outcomes in HCC.
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Affiliation(s)
- Laura Marelli
- Liver Transplantation and Hepatobiliary Medicine Unit, Royal Free Hospital, Pond Street, NW3 2QG London, UK.
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Yamakado K, Nakatsuka A, Kobayashi S, Akeboshi M, Takaki H, Kariya Z, Kinbara H, Arima K, Yanagawa M, Hori Y, Kato H, Sugimura Y, Takeda K. Radiofrequency ablation combined with renal arterial embolization for the treatment of unresectable renal cell carcinoma larger than 3.5 cm: initial experience. Cardiovasc Intervent Radiol 2006; 29:389-94. [PMID: 16502180 DOI: 10.1007/s00270-004-0090-9] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The purpose of the study was to evaluate the feasibility, safety, and therapeutic effects of the combination of renal arterial embolization and radiofrequency (RF) ablation to reinforce the anticancer effect on renal cell carcinomas (RCCs) measuring 3.5 cm or larger. This study was undertaken to evaluate this combined therapy on large RCCs-based tumor geometry. Eleven patients with 12 RCCs 3.5 cm or larger in diameter (3.5-9.0 cm) underwent combined therapy. Two were exophytic tumors, and the remaining 10 tumors had components extending into the renal sinus fat. Tumor vessels were selectively embolized in nine patients and the renal artery was completely embolized in two patients with polyvinyl alcohol or ethanol mixed with iodized oil. RF ablation was percutaneously done under the computed tomographic (CT)-fluoroscopic guidance. Response to treatment was evaluated by dynamic contrast-enhanced CT and magnetic resonance (MR) imaging. Tumor enhancement was eliminated after a single RF session in nine tumors (75%), after two sessions in two tumors (17%), and after four sessions in one tumor (8%). Both exophytic tumors (100%) and 7 of 10 tumors having components in the renal sinus fat (70%) were completely ablated with a single RF session. All tumors remained controlled during a mean follow-up period of 13 months and showed significant reduction in tumor sizes (5.2 +/- 1.7 cm to 3.6 +/- 1.4 cm, p < 0.001). A delayed abscess developed in the ablated lesion in a patient, which was percutaneously drainaged. Combined therapy as described in this report is a feasible, relatively safe, and promising treatment method for large RCCs regardless of tumor geometry.
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Affiliation(s)
- Koichiro Yamakado
- Department of Radiology, Mie University School of Medicine, Tsu, Mie, Japan.
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Zhang C, Deng Y, Huang D, Zhang Q. Dynamic assessment of the focal hepatic lesion in rats using ultrasonic contrast agent. ACTA ACUST UNITED AC 2006; 26:332-3, 368. [PMID: 16961285 DOI: 10.1007/bf02829567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The focal hepatic lesion caused by local injection of absolute alcohol in rats was evaluated with ultrasonic contrast agent and pathologic examination. Twenty adult Wistar rats weighing about 200 g were injected with absolute alcohol (0.05-0.1 mL each one) on the exterior left lobe of the liver under the monitoring of ultrasound. Pulse inversion harmonic imaging was used to evaluate the focal lesion after bolus injection of ultrasonic contrast agent (0.05 mL/200 g) through caudal vein. Seven days later, the focal lesion was studied again as before. The exterior left lobe of liver with focal lesion was incised and underwent pathologic examination. The results showed that all of the focal lesions could be defined clearly after bolus injection of the ultrasonic contrast agent under the mode of pulse inversion harmonic imaging. There was good correlation between the size of the focal lesion measured by ultrasound on the 7th day after the "ablation" under the mode of pulse inversion harmonic imaging and that gotten by pathologic examination (P = 0.39). The focus size measured by ultrasound right after the ablation was larger than that gotten by pathologic examination (P = 0.002). It was concluded that ultrasonic contrast agent plus pulse inversion harmonic imaging could be used to assess the size of the focal hepatic lesion caused by local injection of absolute alcohol in rats.
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Affiliation(s)
- Chao Zhang
- Department of Ultrasound, Tongji Hospital, Tongji Medical Collage, Huazhong University of Science and Technology, Wuhan 430030, China
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Zangos S, Eichler K, Balzer JO, Straub R, Hammerstingl R, Herzog C, Lehnert T, Heller M, Thalhammer A, Mack MG, Vogl TJ. Large-sized hepatocellular carcinoma (HCC): a neoadjuvant treatment protocol with repetitive transarterial chemoembolization (TACE) before percutaneous MR-guided laser-induced thermotherapy (LITT). Eur Radiol 2006; 17:553-63. [PMID: 16896704 DOI: 10.1007/s00330-006-0343-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2005] [Revised: 05/03/2006] [Accepted: 05/22/2006] [Indexed: 02/07/2023]
Abstract
This study aims to evaluate the efficacy and safety of a neoadjuvant treatment protocol with repeated transarterial chemoembolization (TACE) before MR-guided laser-induced thermotherapy (LITT) for large-sized hepatocellular carcinomas (HCC). Repeated TACE (mean, 3.5 treatments per patient) was performed in 48 patients with neoadjuvant intention (the largest lesion was between 50 and 80 mm in diameter, and there were no more than five lesions). For the TACE treatment, we used 10 mg/m(2) mitomycin, 10 ml/m(2) Lipiodol and microspheres. The tumor volume was measured by MRI. Lipiodol retention of the tumors was evaluated with CT. After the diameter of the tumors had decreased to less than 50 mm, the patients were treated with MR-guided LITT 4 to 6 weeks after embolization. Repeated TACE reduced the tumor size in 32 patients (66.7%), forming the basis for performing MR-guided LITT procedures. These patients received one to four laser treatments (mean, 1.9 per patient) for tumor ablation, resulting in a median survival of 36.0 months after the first treatment. For the remaining patients, no reduction in tumor size was achieved in 12 patients and disease progression in 4 patients. Neoadjuvant TACE appears to be an effective treatment of large-sized HCC, which extends the indication for MR-guided LITT.
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MESH Headings
- Aged
- Aged, 80 and over
- Angiography, Digital Subtraction
- Antibiotics, Antineoplastic/administration & dosage
- Carcinoma, Hepatocellular/diagnostic imaging
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/therapy
- Catheter Ablation
- Chemoembolization, Therapeutic/adverse effects
- Chemoembolization, Therapeutic/methods
- Contrast Media
- Echo-Planar Imaging
- Female
- Follow-Up Studies
- Humans
- Hyperthermia, Induced/adverse effects
- Hyperthermia, Induced/methods
- Iodized Oil
- Lasers
- Liver Neoplasms/diagnostic imaging
- Liver Neoplasms/pathology
- Liver Neoplasms/therapy
- Magnetic Resonance Imaging/methods
- Male
- Microspheres
- Middle Aged
- Mitomycin/administration & dosage
- Neoadjuvant Therapy
- Survival Analysis
- Time Factors
- Tomography, X-Ray Computed
- Treatment Outcome
- Tumor Burden/drug effects
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Affiliation(s)
- Stephan Zangos
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
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Solmi L, Nigro G, Roda E. Therapeutic effectiveness of echo-guided percutaneous radiofrequency ablation therapy with a LeVeen needle electrode in hepatocellular carcinoma. World J Gastroenterol 2006; 12:1098-104. [PMID: 16534852 PMCID: PMC4087903 DOI: 10.3748/wjg.v12.i7.1098] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the results of radiofrequency ablation (RFA) in obtaining the necrosis of hepatocellular carcinoma (HCC) in cirrhotic patients and to assess the results of RFA in relation to recurrence of HCC and survival of the treated patients.
METHODS: Fifty-six consecutive cirrhotic patients with 63 HCCs were treated with RFA between May 2000 and May 2004. The diameter of the HCCs ranged from 1 cm to 5 cm (mean 2.8 cm). In all cases RFA was performed with percutaneous approach under ultrasound guidance using expandable needle electrode (LeVeen needle). Treatment efficacy and recurrence were evaluated with dual-phase spiral computed tomography (CT).
RESULTS: Complete necrosis after single or multiple treatment was achieved in 96.8% (61/63) tumors. We observed recurrence after complete necrosis in 23 patients (41%) during a mean follow-up of 32.3 months. The recurrences were local in 2 patients (8.6%) and in different segments in 21 (91.4%). Major complications occurred in 3 patients (4%). During follow-up period, 32 (57.1%) patients died; 15 due to progression of HCC, 11 from liver failure, 3 from esophageal varices bleeding and 3 from the causes not related to liver disease.
CONCLUSION: RFA with LeVeen needle is an effective and safe treatment for HCC < 5 cm in cirrhotic patients. It has yet to be established how far this treatment influences the survival rate of patients. It becomes important to establish treatments to prevent recurrences in different segments, such as interferon therapy.
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Affiliation(s)
- Luigi Solmi
- Gastroenterological Unit, Polyclinic Hospital Sant'Orsola-Malpighi, University School of Medicine, Bologna, Italy.
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Machi J, Bueno RS, Wong LL. Long-term follow-up outcome of patients undergoing radiofrequency ablation for unresectable hepatocellular carcinoma. World J Surg 2006; 29:1364-73. [PMID: 16240062 DOI: 10.1007/s00268-005-7829-6] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The long-term outcome of radiofrequency thermal ablation (RFA) for unresectable hepatocellular carcinoma (HCC) has not been reported. This study was performed to evaluate the long-term survival of patients with unresectable HCC after RFA and to identify possible factors that might affect survival. In this prospective study, 65 patients with unresectable HCC who underwent RFA were followed. A total of 84 RFA operations were performed percutaneously (n = 49), laparoscopically (n = 20), or by open surgery (n = 15), to ablate 191 tumors. Twenty-two patients died within 16 months; otherwise, the follow-up period was at least 16 months, up to 71 months, with median 20.0 months and mean (+/- standard deviation) 24.8 +/- 18.4 months for all patients. Local tumor recurrence developed in 12 of 191 tumors (6.3%) in 11 of 84 operations (13.1%), or 11 of 65 patients (16.9%). New liver and/or extrahepatic recurrence developed in 48 operations (57.1%). The overall median, mean, and 5-year survivals were 40.0 months, 33.7 +/- 2.9 months, and 39.9%. The disease-free survivals were 16.0 month, 32.9 +/- 3.0 months, and 27.9%. Factors that had a significant effect on survival outcome after RFA were TNM cancer stage and the operative approach method employed for RFA. Age, gender, race, etiology, alpha-fetoprotein, previous or subsequent treatment, and liver function (Child-Pugh class) did not affect survival. For patients with unresectable HCC, RFA is an effective and repeatable local treatment that can afford long-term survival, although often with disease recurrence.
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Affiliation(s)
- Junji Machi
- Department of Surgery, University of Hawaii School of Medicine, Kuakini Medical Center and St. Francis Medical Center, 1356 Lusitana Street, Honolulu, Hawaii 96813, USA.
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Pereira P, Boss A, Clasen S, Gouttefangeas C, Schmidt D, Claussen CD. Radiofrequency ablation: the percutaneous approach. Recent Results Cancer Res 2006; 167:39-52. [PMID: 17044295 DOI: 10.1007/3-540-28137-1_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Affiliation(s)
- Philippe Pereira
- Division of Local Therapy, Hoppe-Seyler-Str.3, Tübingen, Germany
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Chen MH, Yang W, Yan K, Gao W, Dai Y, Wang YB, Zhang XP, Yin SS. Treatment efficacy of radiofrequency ablation of 338 patients with hepatic malignant tumor and the relevant complications. World J Gastroenterol 2005; 11:6395-401. [PMID: 16419172 PMCID: PMC4320347 DOI: 10.3748/wjg.v11.i40.6395] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the treatment efficacy of radiofrequency ablation (RFA) of hepatic malignant tumor and the relevant complications.
METHODS: A total of 338 patients with 763 hepatic tumors underwent ultrasound-guided RFA (565 procedures). There were 204 cases of hepatic cellular carcinoma (HCC) with 430 tumors, the mean largest diameter was 4.0 cm. Of them, 48 patients (23.5%) were in stages I-II (UICC Systems) and 156 (76.5%) in stages III-IV There were 134 cases of metastatic liver carcinoma (MLC), with 333 metastases in the liver, the mean diameter was 4.1 cm, the liver metastases of 96 patients (71.6%) came from gastrointestinal tract. Ninety-three percent of the 338 patients were treated using the relatively standard protocol. Crucial attention must be paid to monitor the abnormal changes in ultrasound images as well as the vital signs of the patients to find the possible hemorrhage and peripheral structures injury in time. The tumors were considered as ablated completely, if no viability was found on enhanced CT within 24 h or at 1 mo after RFA. These patients were followed up for 3-57 mo.
RESULTS: The ablation success rate was 93.3% (401/430 tumors) for HCC and was 96.7% (322/333 tumors) for MLC. The local recurrence rate for HCC and MLC was 7.9% (34/430 tumors) and 10.5% (35/333 tumors), respectively. A total of 137 patients (40.5%) underwent 2-11 times of repeated ablations because of tumor recurrence or metastasis. The 1st, 2nd, and 3rd year survival rate was 84.6%, 66.6%, and 63.1%, respectively; the survival rate from 48 patients of I-II stage HCC was 93.7%, 80.4%, and 80.4%, respectively. The major complication rate in this study was 2.5% (14 of 565 procedures), which consisted of 5 hemorrhages, 1 colon perforation, 5 injuries of adjacent structures, 2 bile leakages, and 1 skin burn.
CONCLUSION: RFA, as a minimally invasive local treatment, has become an effective and relatively safe alternative for the patients of hepatic malignant tumor, even of advanced liver tumor, tumor recurrence, and liver metastases. Knowledge about possible complications and their control may increase the treatment efficacy and help to promote the use of RFA technique.
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Affiliation(s)
- Min-Hua Chen
- Department of Ultrasound, Peking University School of Oncology, Haidian District, Beijing 100036, China.
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Veltri A, Moretto P, Doriguzzi A, Pagano E, Carrara G, Gandini G. Radiofrequency thermal ablation (RFA) after transarterial chemoembolization (TACE) as a combined therapy for unresectable non-early hepatocellular carcinoma (HCC). Eur Radiol 2005; 16:661-9. [PMID: 16228211 DOI: 10.1007/s00330-005-0029-9] [Citation(s) in RCA: 157] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2005] [Revised: 08/18/2005] [Accepted: 09/01/2005] [Indexed: 02/06/2023]
Abstract
The treatment of unresectable "non-early" (according to the BCLC classification) hepatocellular carcinoma (HCC) in cirrhotic patients with transcatheter arterial chemoembolization (TACE) followed by radiofrequency ablation (RFA) is retrospectively evaluated and possible prognostic factors of this combined therapy are investigated. Forty-six consecutive cirrhotic patients (Child-Pugh class A or B) with solitary or oligonodular HCC underwent RFA after TACE. The treated lesions were 51 overall (size 30-80 mm, mean 48.9). RFA was performed by a multitined expandable electrodes device after one TACE administration. Local efficacy was evaluated with multiphasic computed tomography (CT) performed an average of 2 months after treatment and then during follow-up. Patient survival rate was also evaluated (follow-up time 1-51 months, mean 15 months). Technical success (defined as complete devascularization during the arterial phase) was achieved in 34/51 lesions (66.7%) at the first CT check and in 29/51 (56.9%) during the succeeding follow-up. Among the considered prognostic factors, only lesion diameter (< or > = 50 mm) was statistically significant in the Fisher's exact test in terms of local control (85.2 vs. 45.8% at first CT, p=.0065; 70.4 vs. 41.7% during follow-up, p=.051). There were two major complications (6.5%): one hepatic failure and one death. A Kaplan-Meier analysis showed survival rates of 89.7% at 12 months and 67.1% at 24 months. Combined therapy for non-early HCC shows a relatively high complete local response (especially in lesions less than 5 cm in diameter) and promising mid-term clinical success. Its overall usefulness has yet to be established by a larger series and risk-benefit analysis.
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Affiliation(s)
- Andrea Veltri
- Institute of Diagnostic and Interventional Radiology, University of Turin, Via Genova 3, 10126, Torino, Italy.
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Mulier S, Ni Y, Jamart J, Ruers T, Marchal G, Michel L. Local recurrence after hepatic radiofrequency coagulation: multivariate meta-analysis and review of contributing factors. Ann Surg 2005; 242:158-71. [PMID: 16041205 PMCID: PMC1357720 DOI: 10.1097/01.sla.0000171032.99149.fe] [Citation(s) in RCA: 543] [Impact Index Per Article: 27.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The purpose of this study was to analyze the factors that influence local recurrence after radiofrequency coagulation of liver tumors. SUMMARY BACKGROUND DATA Local recurrence rate varies widely between 2% and 60%. Apart from tumor size as an important risk factor for local recurrence, little is known about the impact of other factors. METHODS An exhaustive literature search was carried out for the period from January 1, 1990 to January 1, 2004. Only series with a minimal follow-up of 6 months and/or mean follow-up of 12 months were included. Univariate and multivariate meta-analyses were carried out. RESULTS Ninety-five independent series were included, allowing the analysis of the local recurrence rate of 5224 treated liver tumors. In a univariate analysis, tumor-dependent factors with significantly less local recurrences were: smaller size, neuroendocrine metastases, nonsubcapsular location, and location away from large vessels. Physician-dependent favorable factors were: surgical (open or laparoscopic) approach, vascular occlusion, general anesthesia, a 1-cm intentional margin, and a greater physician experience. In a multivariate analysis, significantly less local recurrences were observed for small size (P < 0.001) and a surgical (versus percutaneous) approach (P < 0.001). CONCLUSIONS Radiofrequency coagulation by laparoscopy or laparotomy results in superior local control, independent of tumor size. The percutaneous route should mainly be reserved for patients who cannot tolerate a laparoscopy or laparotomy. The short-term benefits of less invasiveness for the percutaneous route do not outweigh the longer-term higher risk of local recurrence.
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Affiliation(s)
- Stefaan Mulier
- Department of Surgery, University Hospital of Mont-Godinne, Catholic University of Louvain, Yvoir, Belgium
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Kurokohchi K, Watanabe S, Masaki T, Hosomi N, Miyauchi Y, Himoto T, Kimura Y, Nakai S, Deguchi A, Yoneyama H, Yoshida S, Kuriyama S. Comparison between combination therapy of percutaneous ethanol injection and radiofrequency ablation and radiofrequency ablation alone for patients with hepatocellular carcinoma. World J Gastroenterol 2005; 11:1426-32. [PMID: 15770716 PMCID: PMC4305682 DOI: 10.3748/wjg.v11.i10.1426] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: In the present study, the characteristics of PEI-RFA treatment were further elucidated by analyzing the relationship between the volume of coagulated necrosis and the energy requirement for ablation or the amount of ethanol injected into HCC.
METHODS: The volume of coagulated necrosis, total energy requirement and energy requirement for coagulation of per unit volume were examined in the groups of PEI-RFA and RFA alone using the Cool-tip RF system.
RESULTS: The results showed that the volume of coagulated necrosis induced was significantly larger in PEI-RFA group than in routine RFA group, when the total energy administered was comparable in both groups. In PEI-RFA, enlargement of coagulated necrosis was admitted in 3 dimensions and the amount of energy requirement per unit volume of coagulated necrosis was negatively correlated with the amount of ethanol injected into HCC.
CONCLUSION: These results suggest that, compared to RFA alone, PEI-RFA enables to induce comparable coagulated necrosis with smaller energy requirement, and that PEI-RFA is likely to be less invasive than RFA alone irrespective of inducing enhanced coagulated necrosis. Thus, simple prior injection of ethanol may make RFA treatment more effective and less invasive for the treatment of patients with HCC.
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Affiliation(s)
- Kazutaka Kurokohchi
- Third Department of Internal Medicine, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
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