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Mohan PP, Deo S, Liu ZJ, Dikici E, Kaneku H, Chang D, Garcia-Buitrago M, Jalaeian H, Zeynaloo E, Ortiz YY, Li Y, Bhatia S, Velazquez O, Daunert S. Liver Regeneration Following Thermal Ablation Using Nanocarrier Mediated Targeted Mesenchymal Stem Cell Therapy. Cardiovasc Intervent Radiol 2025; 48:233-243. [PMID: 39505737 PMCID: PMC11790787 DOI: 10.1007/s00270-024-03862-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 09/07/2024] [Indexed: 11/08/2024]
Abstract
PURPOSE To test the efficacy of nanocarrier (NC) mediated mesenchymal stem cell (MSC) therapy for liver regeneration following thermal ablation of porcine livers. MATERIALS AND METHODS Liver radiofrequency ablation was performed in 18 swines divided into MSC, MSC + NC and control groups. The test groups received infusion of MSC or MSC + NC labeled with enhanced green fluorescent protein (eGFP) via hepatic artery. MSC + NC group had MSCs coated with dendrimer nanocarrier complexed with I-Domain of lymphocyte function-associated antigen-1 (LFA-1). Nanocarriers direct homing of MSCs by binding to its counterpart protein, intercellular adhesion molecule-1 (ICAM-1), which is overexpressed at the periablation margins from inflammation. Ablation cavity reduction by CT volumetry was used as surrogate marker for liver regeneration. Cell proliferation was assessed with Ki67 and HepPar-1 stains. GFP identified MSC derived cells. RESULTS Total number of ablations in control animals were 13 across 4 animals. In the MSC group, there were 23 ablations across 6 animals, and in MSC + NC group there were 21 ablations across 6 animals. Ablation cavity volume reduction from day 0 to 30 were 64.4 ± 15.0%, 61.5 ± 12.9% and 80.3 ± 9.4% for control, MSC and MSC + NC groups, respectively (MSC + NC vs MSC: p < 0.001, MSC + NC vs. control: p = 0.001). GFP+ cell count at margins was 426.8 ± 193.2 for MSC group and 498.6 ± 235.2 for MSC + NC group (p = 0.01). The mean Ki67 and HepPar-1 staining at margins were 9.81 ± 4.5% and 6.12 ± 4.2% for MSC + NC group versus 7.59 ± 3.7% and 5.09 ± 3.7% for MSC group, respectively (P < 0.001 and P = 0.09, respectively). CONCLUSION Nanocarrier-mediated MSC therapy promotes liver regeneration by engrafting MSCs at ablation margins, potentially making liver-directed therapy viable for patients with severe liver dysfunction. This technology may also benefit other solid organs.
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Affiliation(s)
- Prasoon P Mohan
- Department of Interventional Radiology, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Sapna Deo
- Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Zhao-Jun Liu
- Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Emre Dikici
- Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Hugo Kaneku
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Doyoung Chang
- Department of Interventional Radiology, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Monica Garcia-Buitrago
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Hamed Jalaeian
- Department of Interventional Radiology, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Elnaz Zeynaloo
- Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Yulexi Y Ortiz
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Yan Li
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Shivank Bhatia
- Department of Interventional Radiology, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Omaida Velazquez
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA
| | - Sylvia Daunert
- Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL, USA.
- Department of Interventional Radiology, UMHC-SCC, 1475 NW 12th Ave., Miami, FL, 33136, USA.
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Jeon HJ, Chun HJ, Choi HS, Keum B, Kim HB, Kim JH. Biphasic Regulation of Apoptosis Following Gastric Irreversible Electroporation Using Tissue Immunohistochemistry of Activated Caspase-3 with TUNEL Method. Cancers (Basel) 2024; 16:1389. [PMID: 38611067 PMCID: PMC11010973 DOI: 10.3390/cancers16071389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 03/07/2024] [Accepted: 03/18/2024] [Indexed: 04/14/2024] Open
Abstract
The regulation of apoptosis is the primary goal of ablation therapy. Irreversible electroporation (IRE) is a promising non-thermal tissue ablation-based therapy that induces apoptosis by manipulating electrical conditions. This study aimed to investigate IRE-induced gastric tissue apoptosis in response to changes in the electric field intensity, followed by the repair process. Among the 52 rats used in this study, 24 were used to explore apoptosis, and 28 were used to study regeneration. The apoptosis-to-necrosis ratio of the electrical field strength was evaluated using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and caspase-3 immunohistochemistry. The size of IRE-induced ulcers in the gastric tissue continuously increased with increasing electrical intensity (r2 = 0.830, p < 0.001). The level of apoptosis gradually decreased after peaking at 200 V (1000 V/cm). The size of the 400 V-ablated ulcers continued to decrease, and they were not visible by day 14. The proliferation and migration of epithelial cells with fibroblasts were observed on day 3 and augmented on day 7 post-ablation. This investigation demonstrated the biphasic activation of apoptosis with respect to the electrical field strength. Visually and histologically, IRE-induced gastric ulcers demonstrated complete tissue regeneration after two weeks.
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Affiliation(s)
- Han Jo Jeon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; (H.J.J.); (H.S.C.); (B.K.)
| | - Hoon Jai Chun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; (H.J.J.); (H.S.C.); (B.K.)
| | - Hyuk Soon Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; (H.J.J.); (H.S.C.); (B.K.)
| | - Bora Keum
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; (H.J.J.); (H.S.C.); (B.K.)
| | - Hong Bae Kim
- Department of Biosystems & Biomaterials Science and Engineering, Seoul National University, Seoul 08826, Republic of Korea;
| | - Jong Hyuk Kim
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA;
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Knapen RRMM, Korenblik R, James S, Dams G, Olij B, de Boer SW, van Dam RM, van der Leij C. The Effect of Microwave and Radiofrequency Ablation (MWA/RFA) on Liver Volume in Patients with Primary and Secondary Liver Tumours: A Retrospective Analysis. Cardiovasc Intervent Radiol 2023:10.1007/s00270-023-03503-0. [PMID: 37430014 PMCID: PMC10382361 DOI: 10.1007/s00270-023-03503-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 06/21/2023] [Indexed: 07/12/2023]
Abstract
PURPOSE It is known that thermal liver ablation can induce liver hypertrophy. However, exact impact in liver volume remains unclear. The aim of this study is to assess the influence of radiofrequency or microwave ablation (RFA/MWA) on liver volume in patients with primary and secondary liver lesions. Findings can be relevant in assessing the potential extra benefit of thermal liver ablation in preoperatively performed liver hypertrophy inducing procedures, such as portal vein embolization (PVE). METHODS Between January 2014-May 2022, 69 invasive treatment naïve patients with primary (n = 43) or secondary/metastatic (n = 26) liver lesions (in all segments, except in segments II/III) treated percutaneously by RFA/MWA were included. Total liver volume (TLV), segment II + III volume (serving as "distant liver volume"), ablation zone volume and absolute liver volume (ALV, calculated by subtracting the ablation zone volume from the TLV) were the study outcomes. RESULTS ALV in patients with secondary liver lesions increased to a median percentage of 106.87% (IQR = 99.66-113.03%, p = 0.016), volume of segments II/III increased to a median percentage of 105.81% (IQR = 100.06-115.65%, p = 0.003). ALV and segments II/III in patients with primary liver tumours remained stable, with a median percentage of 98.72% (IQR = 92.99-108.35%, p = 0.856) and 100.43% (IQR = 92.85-109.41%, p = 0.699), respectively. CONCLUSION In patients with secondary liver tumours, ALV and segments II/III increased after MWA/RFA by an average of approximately 6%, while ALV in patients with primary liver lesions remained unchanged. Besides the curative intent, these findings indicate the potential added benefit of thermal liver ablation on FLR hypertrophy inducing procedures in patients with secondary liver lesions. LEVEL OF EVIDENCE Level 3, non-controlled retrospective cohort study.
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Affiliation(s)
- Robrecht R M M Knapen
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
- CARIM, School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
| | - Remon Korenblik
- Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands
- GROW, School for Oncology and Reproduction, Maastricht, The Netherlands
| | - Sinead James
- Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands
- GROW, School for Oncology and Reproduction, Maastricht, The Netherlands
| | - Glenn Dams
- Department of Radiology and Nuclear Medicine, Zuyderland, Sittard, Heerlen, The Netherlands
| | - Bram Olij
- Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands
- GROW, School for Oncology and Reproduction, Maastricht, The Netherlands
| | - Sanne W de Boer
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands
- CARIM, School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
| | - Ronald M van Dam
- Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands
- GROW, School for Oncology and Reproduction, Maastricht, The Netherlands
- Department of General, Visceral and Transplant Surgery, University Hospital Aachen, Aachen, Germany
| | - Christiaan van der Leij
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands
- GROW, School for Oncology and Reproduction, Maastricht, The Netherlands
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Dong L, Cheng Z, Liu F, Yu X, Han Z, Luo Y, Xu H, Chen R, Huang C, Yu J, Liang P. Dynamic changes in liver volume calculated using a three-dimensional visualization system after microwave ablation of hepatocellular carcinomas. Med Phys 2022; 49:4613-4621. [PMID: 35366342 DOI: 10.1002/mp.15641] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 02/22/2022] [Accepted: 03/31/2022] [Indexed: 11/07/2022] Open
Abstract
OBJECTIVES To investigate the changes in liver volume and function after microwave ablation (MWA) of hepatocellular carcinomas (HCCs). MATERIALS AND METHODS We retrospectively analyzed 76 patients with 106 nodules who underwent MWA for HCCs ≤5 cm between January 2015 and September 2017. Liver and ablation volumes were calculated using a three-dimensional visualization system on MRI. Multiple regression analysis was used to estimate the association between the ablation volume and liver volume changes. Deformable image registration (DIR) was performed to confirm the influence of liver volume changes on curative effect evaluation after ablation. RESULTS The initial liver and tumor volumes were 1262.1±259.91 cm3 (range: 864.9∼1966.8) and 2.5 cm3 (interquartile range [IQR]: 1.3∼8.8), respectively. Compared to the initial liver volumes, the entire live volume (ELV) increased by 10.1%±8.93% (range: -4.9%∼46.68%) on the 3rd day after ablation. Subsequently, it recovered to initial level at the 3rd month and maintained its level during the 1-year follow-up. The median total ablation volume was 34.9 cm3 (IQR: 20.4∼65.4) on the 3rd day after ablation, which decreased by 71.2% (IQR: 57.4%∼78.1%) one year after ablation. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (T-Bil) peaked within 3 days after MWA and recovered to normal within 1 month. The ablation volume proportion of the ELV was an independent risk factor for the increase in the ELV and AST, ALT, and T-Bil levels within 3 days after ablation. When DIR was conducted to fuse ablation zone and tumor, the reshaped tumor volumes were enlarged by 40% because of the increase in ELV. CONCLUSIONS MWA of HCCs based on the Milan criteria could induce temporary increases in ELV and RLV within 3 days after ablation, but both parameters recovered to initial levels 3 months after ablation. This indicates that MWA of early-stage HCCs would not lead to liver volume loss and could potentially protect liver function. The liver cannot be treated as an incompressible organ after ablation, and the appropriate deformation constraint should be designed for DIR to evaluate ablation margin accurately. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Linan Dong
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Zhigang Cheng
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Fangyi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Xiaoling Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Zhiyu Han
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Yanchun Luo
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Hongli Xu
- Research Center of Medical Big Data, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Rendong Chen
- School of Mathematical Sciences, Zhejiang University, 38 Zheda Road, Hangzhou, Zhejiang, 310007, China
| | - Chongfei Huang
- School of Mathematical Sciences, Zhejiang University, 38 Zheda Road, Hangzhou, Zhejiang, 310007, China
| | - Jie Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
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Wang Q, Chen S, Yan J, Brismar T, Sparrelid E, Qu C, Ji Y, Chen S, Ma K. Rescue radiofrequency ablation or percutaneous ethanol injection: a strategy for failed RALPPS stage-1 in patients with cirrhosis-related hepatocellular carcinoma. BMC Surg 2021; 21:246. [PMID: 34006263 PMCID: PMC8132340 DOI: 10.1186/s12893-021-01241-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 05/07/2021] [Indexed: 02/08/2023] Open
Abstract
Background The future liver remnant (FLR) faces a risk of poor growth in patients with cirrhosis-related hepatocellular carcinoma (HCC) after stage-1 radiofrequency-assisted ALPPS (RALPPS). The present study presents a strategy to trigger further FLR growth using supplementary radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI). Methods At RALPPS stage-1 the portal vein branch was ligated, followed by intraoperative RFA creating a coagulated avascular area between the FLR and the deportalized lobes. During the interstage period, patients not achieving sufficient liver size (≥ 40%) within 2–3 weeks underwent additional percutaneous RFA/PEI of the deportalized lobes (rescue RFA/PEI) in an attempt to further stimulate FLR growth. Results Seven patients underwent rescue RFA/PEI after RALPPS stage-1. In total five RFAs and eight PEIs were applied in these patients. The kinetic growth rate (KGR) was highest the first week after RALPPS stage-1 (10%, range − 1% to 15%), and then dropped to 1.5% (0–9%) in the second week (p < 0.05). With rescue RFA/PEI applied, KGR increased significantly to 4% (2–5%) compared with that before the rescue procedures (p < 0.05). Five patients proceeded to RALPPS stage-2. Two patients failed: In one patient the FLR remained at a constant level even after four rescue PEIs. The other patient developed metastasis. Except one patient died after RALPPS stage-2, no severe complications (Clavien-Dindo ≥ IIIb) occurred among remaining six patients. Conclusions Rescue RFA/PEI may provide an alternative to trigger further growth of the FLR in patients with cirrhosis-related HCC showing insufficient FLR after RALPPS stage-1. Trial registration Retrospectively registered.
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Affiliation(s)
- Qiang Wang
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology(CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Shu Chen
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China
| | - Jun Yan
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China
| | - Torkel Brismar
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology(CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Ernesto Sparrelid
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Chengming Qu
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China
| | - Yujun Ji
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China
| | - Shihan Chen
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China
| | - Kuansheng Ma
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China.
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Ypsilantis P, Lambropoulou M, Milicevic M, Bulajic P, Karayiannakis A, Zacharoulis D, Simopoulos C. Microscopic assessment of the tissue-sparing potential of radiofrequency-assisted liver resection techniques in a porcine model. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2017; 24:657-666. [PMID: 29032589 DOI: 10.1002/jhbp.513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND The aim of the present study was to microscopically assess the tissue-sparing potential of contemporary radiofrequency-assisted liver resection (RF-LR) techniques. METHODS Twenty-four pigs were subjected to either (1) partial hepatectomy (PH) using the sequential-coagulate-cut (SCC) technique (group SCC, n = 6) using a monopolar electrode, the technique using the bipolar electrode Habib-4X (group H, n = 6) or the "crush-clamp" technique (group CC, n = 6); or (2) sham operation (group Sham, n = 6). At 48 h post-operation, liver parenchyma proximal to the ablation rim was excised for histopathologic examination and immunohistochemical assessment of apoptosis (antibody M30) and inflammatory response (antibodies IL-6, TNFα and NFκB). RESULTS Histopathologic index increased from the 1st to the 4th , the 1st to the 2nd or only the 1st cm from the inner margin of the ablation rim in group SCC, H or CC, respectively. The index was higher in group SCC compared to the other groups. Tissue expression of M30, IL-6, TNFα and NFκB increased in all PH groups, being higher and more expanded in group SCC, H, SCC and SCC, respectively. CONCLUSIONS RF-LR techniques had variable microscopically assessed tissue-sparing effect. The Habib-4X proved to be less injurious compared to the SCC Belgrade technique regarding the severity and extent of tissue damage proximal to the ablation rim.
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Affiliation(s)
- Petros Ypsilantis
- Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Maria Lambropoulou
- Laboratory of Histology and Embryology, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Miroslav Milicevic
- First Surgical Clinic, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Predrag Bulajic
- First Surgical Clinic, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Anastasios Karayiannakis
- Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dimitrios Zacharoulis
- Clinic of Surgery, School of Medicine, University of Thessaly, University Hospital of Larissa, Larissa, Greece
| | - Constantinos Simopoulos
- Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
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Early hemodynamic effects after extended liver radiofrequency ablation. J Surg Res 2014; 195:204-10. [PMID: 25555405 DOI: 10.1016/j.jss.2014.12.003] [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: 08/26/2014] [Revised: 11/23/2014] [Accepted: 12/03/2014] [Indexed: 12/24/2022]
Abstract
BACKGROUND The purpose of the present study was to assess early intestinal and systemic hemodynamic effects after extended radiofrequency ablation (RFA) of the liver in terms of investigating their potential contribution to gut barrier disruption. MATERIALS AND METHODS Ten rabbits were assigned to two groups of five animals each and were subjected to either 30% liver RFA (group RFA-1) or sham operation (group sham-1). Blood flow rate at the superior mesenteric artery (SMA) was monitored for 90 min after operation. Ileal tissue was excised at 48 h for histomorphometric and histopathologic analysis. Eight pigs were assigned to two groups of four animals each and were also subjected to either 30% liver RFA (group RFA-2) or sham operation (group sham-2). A panel of systemic hemodynamic parameters was serially measured up to 90 min after operation. RESULTS In group RFA-1, SMA blood flow rate was lower than that in group sham-1 throughout the study period. Intestinal mucosa atrophy and a deterioration of histopathologic profile were noted in group RFA-1. In group RFA-2, diastolic pulmonary artery pressure was lower (60-90 min), central venous pressure was gradually decreased, arterial pressure was higher (30-90 min), and systemic vascular resistance was higher (30-90 min) than those in group sham-2. No change was noted in the cardiac output. CONCLUSIONS In conclusion, SMA blood flow was reduced during the early post-RFA period, justifying an ischemic insult at the intestine. In addition, a gradual decrease of the preload was counterbalanced by an increase of systemic vascular resistance leaving the cardiac output unaffected.
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Chen MM, Huang YQ, Guo H, Liu Y, Wang JH, Wu JL, Zhang QQ. Preparation, characterization, and potential biomedical application of composite sponges based on collagen from silver carp skin. J Appl Polym Sci 2014. [DOI: 10.1002/app.40998] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Ming-Mao Chen
- Institute of Biomedical and Pharmaceutical Technology; Fuzhou University; Fuzhou 350002 China
| | - Yu-Qing Huang
- Institute of Biomedical and Pharmaceutical Technology; Fuzhou University; Fuzhou 350002 China
| | - Hao Guo
- Institute of Biomedical and Pharmaceutical Technology; Fuzhou University; Fuzhou 350002 China
| | - Yan Liu
- State Key Laboratory of Structural Chemistry; Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences; Fuzhou 350002 China
| | - Jian-Hua Wang
- Institute of Biomedical and Pharmaceutical Technology; Fuzhou University; Fuzhou 350002 China
| | - Jiu-Lin Wu
- Institute of Biomedical and Pharmaceutical Technology; Fuzhou University; Fuzhou 350002 China
| | - Qi-Qing Zhang
- Institute of Biomedical and Pharmaceutical Technology; Fuzhou University; Fuzhou 350002 China
- Key Laboratory of Biomedical Materials of Tianjin; Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College; Tianjin 300192 China
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Ypsilantis P, Lambropoulou M, Kourkoutas I, Pechlivanis A, Simopoulos C. Liver radiofrequency ablation compromises the biological gut barrier. Hum Exp Toxicol 2013; 33:64-73. [PMID: 23703816 DOI: 10.1177/0960327113489049] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
AIM Liver radiofrequency ablation (RFA) has been shown to disrupt the mechanical component of the gut barrier. The aim of the present study was to investigate the consequences of liver RFA on the biological gut barrier in terms of the effects of bile production rate and bowel inflammatory state on intestinal microflora balance. METHOD A total of 25 New Zealand rabbits were assigned to five groups (n = 5 per group): group CBD: subjected to common bile duct (CBD) extracorporeal bypass; group CBD-RFA: subjected to CBD bypass plus one session of open liver RFA; group RFA: subjected to liver RFA; group sham: subjected to sham operation; and group TBD: subjected to total bile deviation (TBD). In groups CBD and CBD-RFA, bile production rate was assessed for 48 h. In groups sham and RFA, measurement of biliary glycine conjugates of cholic and deoxycholic acid levels, histopathologic examination of the non-ablated liver tissue, morphometric analysis, and histopathologic examination of the terminal ileum and microbiological analysis of fecal and tissue samples collected from the jejunum and the cecum (and in group TBD) were performed at 48 h post-operation. RESULTS One session of liver RFA resulted in ablation of 18.7 ± 2.7% of liver weight. Following liver RFA, bile production rate was reduced, while the levels of biliary bile salts were not affected. There was mild injury of the non-ablated liver parenchyma, mild intestinal wall inflammation, intestinal mucosa atrophy, and intestinal microbial population overgrowth. CONCLUSION Reduced in bile production and mild bowel inflammation secondary to liver RFA impaired the biological gut barrier as manifested by intestinal microflora imbalance.
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Affiliation(s)
- P Ypsilantis
- 1Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
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Wang Q, Huang J, Ma K, Li T, Chen M, Wang S, Bie P, He Z. Evaluation of ghost cell survival in the area of radiofrequency ablation. PLoS One 2012; 7:e53158. [PMID: 23300883 PMCID: PMC3534026 DOI: 10.1371/journal.pone.0053158] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 11/26/2012] [Indexed: 12/28/2022] Open
Abstract
Background and Aim Researchers have demonstrated dead cells in radiofrequency ablation (RFA) lesions that have morphological similarities to viable tumor cells and are thus referred to as ghost cells. However, studies on how long ghost cells persist have not been systematically performed. Methods A tumor model was established by implanting VX2 tumor tissue into the livers of 48 New Zealand rabbits. Two weeks later, these tumors were eliminated with RFA. The lesions were resected at 0 weeks, 1 week, 2 weeks, 4 weeks, 8 weeks, or 12 weeks after treatment, and samples were stained either with hematoxylin and eosin (HE) or nicotinamide adenine dinucleotide (NADH). The presence of the cells and the morphological changes that they underwent were examined by light microscopy. Results Four weeks after RFA, there were no obvious morphological changes observed in HE-stained ghost cells, and NADH staining revealed no viable cells. Eight weeks after RFA, the cell structure became indistinct. Twelve weeks after RFA, ghost cells were no longer present. Conclusions The morphological characteristics of ghost cells are maintained for at least 4 weeks, during which time HE staining cannot be used to differentiate ghost cells from residual tumor cells. NADH staining for cell viability is necessary to differentiate residual tumor cells from ghost cells. This evidence adds to our understanding of the mechanisms of RFA when used on solid tumors.
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Affiliation(s)
- Qi Wang
- The Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China
| | - Jiansheng Huang
- The Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China
| | - Kuansheng Ma
- The Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China
- * E-mail:
| | - Tingjun Li
- The Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China
| | - Ming Chen
- The Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China
| | - Shugang Wang
- The Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China
| | - Ping Bie
- The Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China
| | - Zhenping He
- The Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China
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Shibata T, Mizuguchi T, Nakamura Y, Kawamoto M, Meguro M, Ota S, Hirata K, Ooe H, Mitaka T. Low-dose steroid pretreatment ameliorates the transient impairment of liver regeneration. World J Gastroenterol 2012; 18:905-914. [PMID: 22408349 PMCID: PMC3297049 DOI: 10.3748/wjg.v18.i9.905] [Citation(s) in RCA: 2] [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] [Received: 07/04/2011] [Revised: 09/16/2011] [Accepted: 01/18/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To determine if liver regeneration (LR) could be disturbed following radiofrequency (RF) ablation and whether modification of LR by steroid administration occurs. METHODS Sham operation, partial hepatectomy (PH), and partial hepatectomy with radiofrequency ablation (PHA) were performed on adult Fisher 344 rats. We investigated the recovery of liver volume, DNA synthetic activities, serum cytokine/chemokine levels and signal transducers and activators of transcription 3 DNA-binding activities in the nucleus after the operations. Additionally, the effects of steroid (dexamethasone) pretreatment in the PH group (S-PH) and the PHA group (S-PHA) were compared. RESULTS The LR after PHA was impaired, with high serum cytokine/chemokine induction compared to PH, although the ratio of the residual liver weight to body weight was not significantly different. Steroid pretreatment disturbed LR in the S-PH group. On the other hand, low-dose steroid pretreatment improved LR and suppressed tumor necrosis factor (TNF)-α elevation in the S-PHA group, with recovery of STAT3 DNA-binding activity. On the other hand, low-dose steroid pretreatment improved LR and suppressed TNF-α elevation in the S-PHA group, with recovery of STAT3 DNA-binding activity. CONCLUSION LR is disturbed after RF ablation, with high serum cytokine/chemokine induction. Low-dose steroid administration can improve LR after RF ablation with TNF-α suppression.
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Zhao A, Wang T, Yao M, Li H. Effects of chitosan-TPP nanoparticles on hepatic tissue after severe bleeding. ACTA ACUST UNITED AC 2011. [DOI: 10.1016/s1000-1948(11)60054-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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Ypsilantis P, Panopoulou M, Lambropoulou M, Tsigalou C, Pitiakoudis M, Tentes I, Kartali S, Papachristou F, Papadopoulos N, Simopoulos C. Bacterial Translocation in a Rat Model of Large Volume Hepatic Radiofrequency Ablation. J Surg Res 2010; 161:250-8. [DOI: 10.1016/j.jss.2009.01.023] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2008] [Revised: 01/12/2009] [Accepted: 01/16/2009] [Indexed: 01/16/2023]
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Ypsilantis P, Lambropoulou M, Anagnostopoulos C, Tentes I, Tsigalou C, Pitiakoudis M, Kortsaris A, Papadopoulos N, Simopoulos C. Mesna preserves hepatocyte regenerating capacity following liver radiofrequency ablation under Pringle maneuver. J Surg Res 2009; 169:44-50. [PMID: 20080247 DOI: 10.1016/j.jss.2009.10.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2009] [Revised: 09/14/2009] [Accepted: 10/01/2009] [Indexed: 11/29/2022]
Abstract
BACKGROUND The objectives of the present study were to test the hypothesis that hepatocyte regenerating activity induced by radiofrequency ablation (RFA) of the liver is attenuated when performed under Pringle maneuver, and to investigate the potentially protective effect of mesna prophylactic administration. MATERIALS AND METHODS Wistar rats were subjected to liver RFA (group RFA), RFA plus Pringle maneuver for 30 min (group RFA+P), RFA plus Pringle plus mesna (400mg/kg, per os, 3h prior to operation) (group RFA+P+M), Pringle only (group P), or sham operation (group S) after midline laparotomy. At 1h, liver oxidative state (glutathione to glutathione disulfide ratio-GSH/GSSG) and nuclear factor κB (NF-κB) activity were assessed in liver specimens. At 1, 3, and 6h, the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in blood serum. At 24h, 48 h, 1 wk, and 3 wk, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured in blood serum and the histopathologic profile and hepatocyte mitotic activity were assessed in liver specimens. RESULTS Mitotic activity was low but sustained in groups RFA and RFA+P+M, more intense in group P, while suppressed in group RFA+P. Histopathologic profile was deteriorated with lesions being more intense in group RFA+P but significantly less severe in group RFA+P+M. Oxidative stress was equally induced in all experimental groups. NF-κB was activated in groups RFA, RFA+P, and P, but not in group RFA+P+M. IL-6 and TNF-α serum levels were increased; the levels were significantly higher in group RFA+P, while lower in group RFA+P+M. Serum transaminases levels were increased during the first 48 h. CONCLUSIONS Hepatocyte regenerating activity is suppressed following liver RFA under Pringle maneuver. Prophylactic administration of mesna preserves hepatocyte regenerating capacity by attenuating acute inflammatory response and minimizing hepatic tissue injury in the non-ablated liver parenchyma.
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Affiliation(s)
- Petros Ypsilantis
- Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
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