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Frenkel N, Poghosyan S, van Wijnbergen JW, Rinkes IB, Kranenburg O, Hagendoorn J. Differential cytokine and chemokine expression after ablation vs. resection in colorectal cancer liver metastasis. Surg Open Sci 2024; 18:29-34. [PMID: 38318321 PMCID: PMC10838949 DOI: 10.1016/j.sopen.2024.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 11/23/2023] [Accepted: 01/10/2024] [Indexed: 02/07/2024] Open
Abstract
Background Surgical resection remains the main curative treatment for colorectal liver metastases (CRLM). Radiofrequency ablation (RFA) is increasingly employed for small, deep lying or otherwise inoperable lesions. However, RFA can induce pro-tumorigenic effects on residual tumor cells, hereby possibly promoting tumor recurrence. Contrastingly, post-RFA tumor debris as an antigen source can also generate anti-cancer immune responses. Utilizing this, current studies on combining RFA with immune therapy appear promising. Here, in an attempt to shed light on this controversy, cytokines involved in inflammation, (lymph)angiogenesis, immune cell recruitment and tumor cell invasion were investigated post-RFA versus post-resection in CRLM patients. Methods Cytokine and chemokine serum levels pre-operation, 4 h and 24 h post-operation were analyzed in CRLM patients undergoing RFA (n = 8) or partial hepatectomy (n = 9) using Multiplex immunoassays. Statistical analyses were performed between as well as within individual intervention groups. Results Post-RFA, significantly increased levels of acute phase proteins SAA1 and S100A8, IL-6, IL-1Ra, MIP3b (CCL19) and MMP9 were observed along with decreases in Fibronectin, MCP-1 (CCL2), and Tie-2. Post-resection, increased levels of PDGFbb, I309 (CCL1), Apelin, MIF, IL-1b and TNFα were seen. All p-values <0.05. Conclusion Pro-inflammatory responses mediated by different cytokines were seen after both RFA and resection, possibly influencing residual tumor cells and tumor recurrence. As both ablation and resection trigger inflammation and immune cell recruitment (albeit via distinct mechanisms), these data suggest that further research may explore combining immune therapy with not only RFA but also resection. Key message Analysis of patients' serum after radiofrequency ablation versus resection of colorectal liver metastases (CRLM) showed that these interventions trigger inflammation and immune cell recruitment, via different cyto- and chemokine pathways. This suggests a possible future strategy of combining immune therapy with not only ablative techniques but also with resection of CRLM.
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Affiliation(s)
| | | | - Jan Willem van Wijnbergen
- Laboratory for Translational Oncology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584CX Utrecht, the Netherlands
| | - Inne Borel Rinkes
- Laboratory for Translational Oncology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584CX Utrecht, the Netherlands
| | - Onno Kranenburg
- Laboratory for Translational Oncology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584CX Utrecht, the Netherlands
| | - Jeroen Hagendoorn
- Laboratory for Translational Oncology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584CX Utrecht, the Netherlands
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Peng X, Xing J, Zou H, Pang M, Huang Q, Zhou S, Li K, Ge M. Postoperative SIRS after thermal ablation of HCC: Risk factors and short-term prognosis. Heliyon 2024; 10:e25443. [PMID: 38327471 PMCID: PMC10847922 DOI: 10.1016/j.heliyon.2024.e25443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 01/15/2024] [Accepted: 01/26/2024] [Indexed: 02/09/2024] Open
Abstract
Background We aimed to explore the potential risk factors and short-term prognosis for SIRS after thermal ablation of hepatocellular carcinoma (HCC). Methods Data from patients with HCC who underwent thermal ablation in the Third Affiliated Hospital of Sun Yat-sen University between January 2015 and August 2021 were retrieved from the perioperative database. Pre-, intra- and postoperative data between SIRS group and non-SIRS group were compared and multivariate logistic regression analysis was performed to identify the risk factors for SIRS after thermal ablation. Results A total of 1491 patients were enrolled and 234 (15.7 %) patients developed SIRS after thermal ablation. Compared with those without SIRS, patients with SIRS had a longer hospital stay, higher hospitalization costs and higher risk of more severe postoperative complications. In the multivariate logistic regression analysis, current smoking (OR 1.58, 95 %CI 1.09-2.29), decreased HCT (OR 1.51,95 %CI 1.11-2.04), NEUT < 1.5 × 109/L(OR 1.74, 95 %CI 1.14-2.65), NEUT% < 0.5 or > 0.7 (OR 1.36, 95 %CI 1.01-1.83) and PT > 16.3s (OR 2.42, 95 %CI 1.57-3.74) were significantly associated with postoperative SIRS. Conclusions Current smoking, decreased HCT, neutropenia, abnormal percentage of neutrophils and prolonged PT are the independent risk factors for SIRS after thermal ablation of HCC, which worsens outcomes of patients. This study can help identify high-risk population and guide appropriate care so as to reduce the incidence of postoperative SIRS.
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Affiliation(s)
- Xiaorong Peng
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jibin Xing
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hao Zou
- Department of Anesthesiology, Foshan Women and Children Hospital, Foshan, China
| | - Mengya Pang
- Department of Anesthesiology, Shenzhen Children's Hospital, Shenzhen, China
| | - Qiannan Huang
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shaoli Zhou
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Kai Li
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Mian Ge
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Arrichiello A, Di Meglio L, Angileri SA, Duka E, Gurgitano M, Rodà GM, Ierardi AM, Carrafiello G. Liver Cancer Interventions. MULTIMODALITY IMAGING AND INTERVENTION IN ONCOLOGY 2023:189-199. [DOI: 10.1007/978-3-031-28524-0_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Huang Q, Pang M, Zeng Q, He X, Zheng R, Ge M, Li K. The frequency and risk factors of major complications after thermal ablation of liver tumours in 2,084 ablation sessions. Front Surg 2022; 9:1010043. [PMID: 36189384 PMCID: PMC9520062 DOI: 10.3389/fsurg.2022.1010043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 08/29/2022] [Indexed: 12/24/2022] Open
Abstract
Background To assess the frequency of major complications after thermal ablation of liver tumours and to determine risk factors for adverse events. Methods A retrospective study was conducted between January 2015 and January 2021. A total of 2,084 thermal ablation sessions in 1,592 patients with primary and metastatic liver tumours were evaluated. The frequency of major complications was evaluated according to the Society of Interventional Radiology Standards, and putative predictors of adverse events were analysed using simple and multivariate logistic regression. Results Thermal ablation-related mortality was 0.1% (2/2,084), with an overall major complication rate of 5.6% (117/2,084). The most frequent major complication was symptomatic pleural effusion (2.9%, 60/2,084). Multivariate logistic regression analysis revealed that a total maximum diameter of lesions >3 cm, microwave ablation (MWA) and MWA combined with radiofrequency ablation, intrahepatic cholangiocarcinoma and postoperative systemic inflammatory response syndrome were independent prognostic factors for major complications. Conclusions Thermal ablation of liver tumours is a safe procedure with an acceptable incidence of major complications. The risk factors identified in this study will help to stratify high-risk patients.
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Affiliation(s)
- Qiannan Huang
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Mengya Pang
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qingjing Zeng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xuqi He
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Rongqin Zheng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Mian Ge
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Correspondence: Kai Li Mian Ge
| | - Kai Li
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Correspondence: Kai Li Mian Ge
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Tonguc T, Strunk H, Gonzalez-Carmona MA, Recker F, Lütjohann D, Thudium M, Conrad R, Becher MU, Savchenko O, Davidova D, Luechters G, Mustea A, Strassburg CP, Attenberger U, Pieper CC, Jenne J, Marinova M. US-guided high-intensity focused ultrasound (HIFU) of abdominal tumors: outcome, early ablation-related laboratory changes and inflammatory reaction. A single-center experience from Germany. Int J Hyperthermia 2021; 38:65-74. [PMID: 34420445 DOI: 10.1080/02656736.2021.1900926] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
INTRODUCTION High-intensity focused ultrasound (HIFU) is an innovative noninvasive procedure for local ablation of different benign and malignant tumors. Preliminary data of animal studies suggest an ablation-associated immune response after HIFU that is induced by cell necrosis and release of intracellular components. The aim of this study is to evaluate if a HIFU-induced early sterile inflammatory reaction is initiated after ablation of uterine fibroids (UF) and pancreatic carcinoma (PaC) which might contribute to the therapeutic effect. MATERIAL AND METHODS A hundred patients with PaC and 30 patients with UF underwent US-guided HIFU treatment. Serum markers of inflammation (leukocytes, CRP, IL-6) and LDH in both collectives as well as tumor markers CA 19-9, CEA and CYFRA in PaC patients were determined in sub-cohorts before and directly after HIFU (0, 2, 5 and 20 h post-ablation) as well as at 3, 6, 9 and 12 months follow-up. Peri-/post interventional imaging included contrast-enhanced MRI of both cohorts and an additional CT scan of PaC patients. RESULTS An early post-ablation inflammatory response was observed in both groups with a significant increase of leukocytes, CRP and LDH within the first 20 h after HIFU. Interestingly, IL-6 was increased at 20 h after HIFU in PaC patients. A significant reduction of tumor volumes was observed during one year follow-up (p < .001) for both tumor entities demonstrating effective treatment outcome. CONCLUSION Tumor ablation with HIFU induces an early sterile inflammation that might serve as a precondition for long-term tumor immunity and a sustainable therapeutic effect.
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Affiliation(s)
- Tolga Tonguc
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Holger Strunk
- Department of Radiology, Städtisches Klinikum Solingen, Solingen, Germany
| | | | - Florian Recker
- Department of Gynaecology and Gynaecological Oncology, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Dieter Lütjohann
- Department of Clinical Pharmacology and Laboratory Medicine, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Marcus Thudium
- Department of Anesthesiology, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Rupert Conrad
- Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Marc U Becher
- Department of Internal Medicine I, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Oleksandr Savchenko
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Darya Davidova
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Guido Luechters
- Center for Development Research (ZEF), University Bonn, Bonn, Germany
| | - Alexander Mustea
- Department of Gynaecology and Gynaecological Oncology, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Ulrike Attenberger
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Claus C Pieper
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, University Bonn, Bonn, Germany
| | - Jürgen Jenne
- Fraunhofer Institute for Digital Medicine, MEVIS, Bremen, Germany
| | - Milka Marinova
- Department of Diagnostic and Interventional Radiology, University Hospital Bonn, University Bonn, Bonn, Germany
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Kirdak T, Uysal E, Sezgin E, Cecen GS, Cavun S. Inflammatory response markers in rats undergoing abdominal surgical procedures. Ann Gastroenterol 2020; 33:528-535. [PMID: 32879601 PMCID: PMC7406820 DOI: 10.20524/aog.2020.0511] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 06/09/2020] [Indexed: 01/01/2023] Open
Abstract
Background The aim of this study was to determine the effectiveness of cortisol, interleukin (IL)-6, C-reactive protein (CRP), and white blood cell (WBC) count as inflammatory markers to evaluate the postoperative inflammatory response associated with various abdominal surgical procedures in rats. Methods Wistar albino rats (N=152) were randomly assigned to 7 groups: control, hepatectomy, splenectomy, nephrectomy, colectomy, gastrectomy, and sham. Apart from the control group, each group was then divided into 3 subgroups: 6th, 24th and 48th h. Thus, a total of 19 groups were defined, each including 8 rats. At the 6th, 24th and 48th h following the surgical procedures blood samples from each rat were collected. The plasma concentrations of IL- 6, cortisol, CRP, and WBC were measured. Results Both the surgery category and the elapsed time after the surgery had a significant effect on IL-6 levels (P<0.0001). Blood CRP levels were primarily determined by the surgery category (P<0.0001). Neither surgery nor the elapsed time had a significant effect on the cortisol levels. The elapsed time after surgery was the major factor that influenced the differences in WBC count among the surgery groups (P<0.0001). Conclusions Our results cumulatively indicate that the levels of IL-6, CRP, and cortisol and WBC count change at different time points after several abdominal surgical procedures. Cortisol level is not related to the type of surgical procedure or the elapsed time, while WBC count decreases with the elapsed time. None of the changes in the markers investigated in this study is specifically related to the category of abdominal surgical procedure.
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Affiliation(s)
- Türkay Kirdak
- Department of General Surgery, Uludag University School of Medicine, Bursa
| | - Erdal Uysal
- Department of General Surgery, Gaziantep, Sanko University School of Medicine
| | - Efe Sezgin
- Department of Food Engineering, Izmir, lzmir lnstitute of Technology, Laboratory of Nutrigenomics and Epidemiology
| | - Gülce Sevdar Cecen
- Department of Medical Pharmacology, Uludag University School of Medicine, Bursa, Turkey
| | - Sinan Cavun
- Department of Medical Pharmacology, Uludag University School of Medicine, Bursa, Turkey
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CIRSE Standards of Practice on Thermal Ablation of Liver Tumours. Cardiovasc Intervent Radiol 2020; 43:951-962. [PMID: 32382856 DOI: 10.1007/s00270-020-02471-z] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 03/27/2020] [Indexed: 02/06/2023]
Abstract
This CIRSE Standards of Practice document reviews current literature and provides best practices for image guided thermal ablation of liver tumours, including radiofrequency, microwave and cryoablation techniques.
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8
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Long-term outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma: Retrospective case-matched study. INTERNATIONAL JOURNAL OF SURGERY OPEN 2020. [DOI: 10.1016/j.ijso.2020.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Wang S, Yang M, Yang X, Xu L, Ke S, Ding X, Sun W, Gao J. Endothelial pyroptosis underlies systemic inflammatory response following radiofrequency ablation of hepatic hemangiomas. Scandinavian Journal of Clinical and Laboratory Investigation 2019; 79:619-628. [PMID: 31710248 DOI: 10.1080/00365513.2019.1689428] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
This study investigated the relationship between endothelial pyroptosis and the occurrence of systemic inflammatory response (SIR) after radiofrequency (RF) ablation of hepatic hemangiomas. Thirty-two patients with hepatic hemangiomas were treated with RF ablation and blood samples of the patients were collected at different time points. Immunohistochemistry staining was performed to evaluate the expression of caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 in hepatic hemangioma and subablated hemangioma tissue. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were treated with sub-ablative hyperthermia with or without the addition of caspase-1 inhibitor, Ac-YVAD-CMK in the medium. Lactate dehydrogenase (LDH), IL-18, IL-1β, caspase-1 and GSDMD were measured by enzyme-linked immunosorbent assay, real-time PCR and Western blot methods. An elevation of general SIR parameters (CRP and WBC), pyroptosis-related inflammatory cytokines (IL-1β and IL-18) and LDH were observed 1-day post-RF ablation and their peak values were significantly correlated with ablated volume (p < .001) and ablation time (p < .001). Moreover, levels of pyroptosis-related inflammatory cytokines correlated well with general SIR parameters, respectively (p < .001). Immunohistochemical analysis showed the increased expression of caspase-1, GSDMD, IL-18 and IL-1β in the endothelial cells of subablated hemangioma. In vitro experiments showed that subablative hyperthermia induced the caspase-1-associated endothelial pyroptosis and Ac-YVAD-CMK attenuated pyroptosis. In conclusion, SIR in patients treated by RF ablation for hepatic hemangiomas was significantly associated with the ablated volume and ablation time and endothelial pyroptosis may involve in the occurrence of SIR following RF ablation of hepatic hemangiomas.
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Affiliation(s)
- Shaohong Wang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Mengmeng Yang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xu Yang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Li Xu
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Shan Ke
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xuemei Ding
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Jun Gao
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
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10
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Kim DK, Kwon JH, Won JY, Han K, Kim GM, Kim MD, Lee DY. Ablation Volume Measurement After Percutaneous Cryoablation Using a Two-cryo-probe Technique for Small Hepatocellular Carcinomas. Cardiovasc Intervent Radiol 2018; 42:220-229. [DOI: 10.1007/s00270-018-2084-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Accepted: 09/19/2018] [Indexed: 12/25/2022]
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Impact of Elevated Circulating Histones on Systemic Inflammation after Radiofrequency Ablation in Lung Cancer Patients. BIOMED RESEARCH INTERNATIONAL 2017; 2017:6894832. [PMID: 29457035 PMCID: PMC5804403 DOI: 10.1155/2017/6894832] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 11/26/2017] [Indexed: 11/17/2022]
Abstract
Background This study investigated the changes of circulating histones following radiofrequency ablation (RFA) in lung cancer patients and their impact on systemic inflammation. Methods Serial blood samples were obtained from a total of 65 primary and metastatic lung cancer patients undergoing RFA at 2 time points: pre-RFA and post-RFA within 48 h. Circulating histones, myeloperoxidase (MPO), and multiple inflammatory cytokines were measured. Moreover, the patient's sera were incubated overnight with human monocytic U937 cells in the presence or absence of anti-histone antibody, and cytokine production was evaluated. Results Compared to pre-RFA, there was a significant increase in circulating histones within 48 h after RFA, along with an elevation of MPO and several canonical inflammatory cytokines. Circulating histones were correlated with these inflammatory markers. Notably, compared to the sera obtained before RFA, the patients' post-RFA sera significantly stimulated cytokine production in the supernatant of U937 cells, which could be prevented by anti-histone antibody, thereby confirming a cause-effect relationship between circulating histones and systemic inflammation. Conclusions This study showed that circulating histones may serve as a marker indicating RFA-related systemic inflammation as well as represent a therapeutic target for resolution of inflammation.
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Takahashi Y, Matsutani N, Nakayama T, Dejima H, Uehara H, Kawamura M. Immunological effect of local ablation combined with immunotherapy on solid malignancies. CHINESE JOURNAL OF CANCER 2017; 36:49. [PMID: 28592286 PMCID: PMC5463413 DOI: 10.1186/s40880-017-0216-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 05/30/2017] [Indexed: 02/07/2023]
Abstract
Recent comprehensive investigations clarified that immune microenvironment surrounding tumor cells are deeply involved in tumor progression, metastasis, and response to treatment. Furthermore, several immunotherapeutic trials have achieved successful results, and the immunotherapeutic agents are available in clinical practice. To enhance their demonstrated efficacy, combination of immunotherapy and ablation has begun to emerge. Local ablations have considerable advantages as an alternative therapeutic option, especially its minimal invasiveness. In addition, local ablations have shown immune-regulatory effect in preclinical and clinical studies. Although the corresponding mechanisms are still unclear, the local ablations combined with immunotherapy have been suggested in the treatment of several solid malignancies. This article aims to review the published data on the immune-regulatory effects of local ablations including stereotactic body radiotherapy, cryoablation, radiofrequency ablation, and high-intensity-focused ultrasound. We also discuss the value of local ablations combined with immunotherapy. Local ablations have the potential to improve future patient outcomes; however, the effectiveness and safety of local ablations combined with immunotherapy should be further investigated.
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Affiliation(s)
- Yusuke Takahashi
- Department of General Thoracic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan.
| | - Noriyuki Matsutani
- Department of General Thoracic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Takashi Nakayama
- Department of General Thoracic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Hitoshi Dejima
- Department of General Thoracic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Hirofumi Uehara
- Department of General Thoracic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Masafumi Kawamura
- Department of General Thoracic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
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Kwok N, Lee SR, Arellano RS. Postloco-Regional Therapy Imaging of the Liver. Semin Roentgenol 2016; 51:378-383. [PMID: 27743572 DOI: 10.1053/j.ro.2016.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Nathan Kwok
- Tufts University School of Medicine, Boston, MA
| | - Stephen R Lee
- Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA
| | - Ronald S Arellano
- Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA.
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Interventional oncology: pictorial review of post-ablation imaging of liver and renal tumors. Abdom Radiol (NY) 2016; 41:677-705. [PMID: 26934894 DOI: 10.1007/s00261-016-0665-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Percutaneous image-guided ablation is now commonly performed in many institutions for the treatment of hepatocellular carcinoma, liver metastases, and renal cell carcinoma in select patients. Accurate interpretation of post-ablation imaging is of supreme importance because treatment algorithms for these diseases rely heavily on imaging to guide management decisions. The purpose of this pictorial essay is to provide abdominal imagers with a review of the indications for percutaneous ablation in the abdomen, a basic overview of ablation modalities in clinical use today, the expected post-ablation imaging findings in the liver and kidney, and potential complications of hepatic and renal ablation procedures.
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15
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Paiella S, Salvia R, Ramera M, Girelli R, Frigerio I, Giardino A, Allegrini V, Bassi C. Local Ablative Strategies for Ductal Pancreatic Cancer (Radiofrequency Ablation, Irreversible Electroporation): A Review. Gastroenterol Res Pract 2016; 2016:4508376. [PMID: 26981115 PMCID: PMC4770121 DOI: 10.1155/2016/4508376] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 10/28/2015] [Accepted: 01/13/2016] [Indexed: 02/07/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. Locally advanced pancreatic cancer (LAPC) accounts for the 40% of the new diagnoses. Current treatment options are based on chemo- and radiotherapy regimens. Local ablative techniques seem to be the future therapeutic option for stage-III patients with PDAC. Radiofrequency Ablation (RFA) and Irreversible Electroporation (IRE) are actually the most emerging local ablative techniques used on LAPC. Initial clinical studies on the use of these techniques have already demonstrated encouraging results in terms of safety and feasibility. Unfortunately, few studies on their efficacy are currently available. Even though some reports on the overall survival are encouraging, randomized studies are still required to corroborate these findings. This study provides an up-to-date overview and a thematic summary of the current available evidence on the application of RFA and IRE on PDAC, together with a comparison of the two procedures.
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Affiliation(s)
- Salvatore Paiella
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
| | - Marco Ramera
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Girelli
- Pancreatic Surgical Unit, Casa di Cura Pederzoli, Peschiera del Garda, Verona, Italy
| | - Isabella Frigerio
- Pancreatic Surgical Unit, Casa di Cura Pederzoli, Peschiera del Garda, Verona, Italy
| | - Alessandro Giardino
- Pancreatic Surgical Unit, Casa di Cura Pederzoli, Peschiera del Garda, Verona, Italy
| | - Valentina Allegrini
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
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Gu T, Ge Y, Song Y, Fu Z, Zhang Y, Wang G, Shao S, Wen T. Hepatic radiofrequency ablation causes an increase of circulating histones in patients with hepatocellular carcinoma. Scand J Clin Lab Invest 2015; 75:621-7. [PMID: 26305424 DOI: 10.3109/00365513.2015.1050689] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Radiofrequency ablation (RFA) has been increasingly accepted for the treatment of hepatocellular carcinoma (HCC). However, RFA has been associated with an obvious systemic inflammatory response, but little is known about the underlying mechanisms. Circulating histones are recently identified as pivotal inflammatory mediators. Hence, we investigated whether circulating histones are involved in RFA-related inflammation. METHODS Serial blood samples were collected from 42 HCC patients undergoing RFA at 3 time points: pre-RFA, post-RFA (within 24 h), and in 4-week follow up after RFA. Plasma histones, myeloperoxidase (MPO), inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α), liver damage parameters (ALT, AST), and creatinine were measured. RESULTS Compared to pre-RFA (0.837 μg/ml), there was a significant increase in the levels of circulating histones within 24 h post-RFA (4.576 μg/ml, p < 0.0001); histones decreased to pre-RFA levels in 4-week follow up after RFA. Meanwhile, MPO, IL-6, and IL-10 were elevated remarkably within 24 h post-RFA, indicative of an occurrence of the inflammatory response. Notably, histone levels correlated well with MPO (r = 0.5678), IL-6 (r = 0.4851), and IL-10 (r = 0.3574), respectively. In addition, there was a significant damage of liver function in patients within 24 h post-RFA, evidenced by the increased levels of ALT and AST. No changes in creatinine levels were observed. CONCLUSIONS These data demonstrate that circulating histones are excessively released in HCC patients treated with RFA, which may lead to systemic inflammation by stimulating neutrophil activation and promoting cytokine production. Circulating histones may act as a novel marker to indicate the extent of inflammation related to RFA.
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Affiliation(s)
- Tao Gu
- a Department of Oncology , First Hospital of Qinhuangdao , Qinhuangdao, Hebei Province, P.R. China
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17
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Watt DG, Horgan PG, McMillan DC. Routine clinical markers of the magnitude of the systemic inflammatory response after elective operation: a systematic review. Surgery 2015; 157:362-80. [PMID: 25616950 DOI: 10.1016/j.surg.2014.09.009] [Citation(s) in RCA: 237] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Accepted: 09/08/2014] [Indexed: 01/10/2023]
Abstract
BACKGROUND Operative injury to the body from all procedures causes a stereotypical cascade of neuroendocrine, cytokine, myeloid, and acute phase responses. This response has been examined commonly by the use of cortisol, interleukin-6 (IL-6), white cell count, and C-reactive protein (CRP). We aimed to determine which markers of the systemic inflammatory response were useful in determining the magnitude of injury after elective operations. METHODS A systematic review of the literature was performed using surgery, endocrine response, systemic inflammatory response, cortisol, IL-6, white cell count, and CRP. For each analyte the studies were grouped according to whether the operative injury was considered to be minor, moderate, or major and then by the operative procedure. RESULTS A total of 164 studies were included involving 14,362 patients. The IL-6 and CRP responses clearly were associated with the magnitude of operative injury and the invasiveness of the operative procedure. For example, the peak CRP response increased from 52 mg/L with cholecystectomy to 123 mg/L with colorectal cancer resection, 145 mg/L with hip replacement, 163 mg/L after abdominal aortic aneurysm repair, and 189 mg/L after open cardiac surgery. There also appeared to be a difference between minimally invasive/laparoscopic and open procedures such as cholecystectomy (27 vs 80 mg/L), colorectal cancer resection (97 vs 133 mg/L), and aortic aneurysm repair (132 vs 180 mg/L). CONCLUSION Peak IL-6 and CRP concentrations consistently were associated with the magnitude of operative injury and operative procedure. These markers may be useful in the objective assessment of which components of Enhanced Recovery after Surgery are likely to improve patient outcome and to assess the possible impact of operative injury on immune function.
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Affiliation(s)
- David G Watt
- Academic Unit of Colorectal Surgery, School of Medicine-University of Glasgow, Glasgow Royal Infirmary, Glasgow, Scotland.
| | - Paul G Horgan
- Academic Unit of Colorectal Surgery, School of Medicine-University of Glasgow, Glasgow Royal Infirmary, Glasgow, Scotland
| | - Donald C McMillan
- Academic Unit of Colorectal Surgery, School of Medicine-University of Glasgow, Glasgow Royal Infirmary, Glasgow, Scotland
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18
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Schneider T, Sevko A, Heussel CP, Umansky L, Beckhove P, Dienemann H, Safi S, Utikal J, Hoffmann H, Umansky V. Serum inflammatory factors and circulating immunosuppressive cells are predictive markers for efficacy of radiofrequency ablation in non-small-cell lung cancer. Clin Exp Immunol 2015; 180:467-74. [PMID: 25644608 DOI: 10.1111/cei.12596] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2015] [Indexed: 12/20/2022] Open
Abstract
In recent years, percutaneous radiofrequency ablation (RFA) has been developed as a new tool in the treatment of non-small-cell lung cancer (NSCLC) in non-surgical patients. There is growing evidence that RFA-mediated necrosis can modulate host immune responses. Here we analysed serum inflammatory factors as well as immunosuppressive cells in the peripheral blood to discover possible prognostic indicators. Peripheral blood and serum samples were collected before RFA and within 3 months after the treatment in a total of 12 patients. Inflammatory cytokines and growth factors were measured in serum by the Bio-Plex assay. Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs ) were evaluated in the peripheral blood via flow cytometry. In patients developing local or lymphogenic tumour relapse (n=4), we found an early significant increase in the concentration of tumour necrosis factor (TNF)-α as well as chemokine (C-C motif) ligand (CCL)-2 and CCL-4 compared to patients without relapse (n=4) and healthy donors (n=5). These changes were associated with an elevated activity of circulating MDSC indicated by an increased nitric oxide (NO) production in these cells. Elevated serum levels of TNF-α, CCL-2 and CCL-4 associated with an increased NO production in circulating MDSCs might be an early indicator of the incomplete RFA and subsequently a potential tumour relapse in NSCLC.
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Affiliation(s)
- T Schneider
- Department of Thoracic Surgery, St Vincentius Kliniken, Karlsruhe, Germany
| | - A Sevko
- Skin Cancer Unit, German Cancer Research Center, Heidelberg and Department of Dermatology, Venerology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Heidelberg, Germany
| | - C P Heussel
- Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik, Heidelberg University, Heidelberg, Germany
| | - L Umansky
- Department of Translational Immunology, German Cancer Research Center, Heidelberg, Germany
| | - P Beckhove
- Department of Translational Immunology, German Cancer Research Center, Heidelberg, Germany
| | - H Dienemann
- Department of Thoracic Surgery, Thoraxklinik, Heidelberg University, Heidelberg, Germany
| | - S Safi
- Department of Thoracic Surgery, Thoraxklinik, Heidelberg University, Heidelberg, Germany
| | - J Utikal
- Skin Cancer Unit, German Cancer Research Center, Heidelberg and Department of Dermatology, Venerology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Heidelberg, Germany
| | - H Hoffmann
- Department of Thoracic Surgery, Thoraxklinik, Heidelberg University, Heidelberg, Germany
| | - V Umansky
- Skin Cancer Unit, German Cancer Research Center, Heidelberg and Department of Dermatology, Venerology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Heidelberg, Germany
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Orlacchio A, Bolacchi F, Chegai F, Bergamini A, Costanzo E, Del Giudice C, Angelico M, Simonetti G. Comparative evaluation of percutaneous laser and radiofrequency ablation in patients with HCC smaller than 4 cm. Radiol Med 2013; 119:298-308. [PMID: 24277510 DOI: 10.1007/s11547-013-0339-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2012] [Accepted: 02/24/2013] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This study was done to compare percutaneous laser ablation (PLA) and radiofrequency thermoablation (RFA) for the treatment of hepatocellular carcinoma (HCC) ≤ 4 cm, in patients with liver cirrhosis. MATERIALS AND METHODS Thirty patients with single HCC ≤ 4 cm in diameter were randomly assigned to one of two treatments: 15 patients were treated with PLA, using a multifibre system connected to a neodymium yttrium-aluminium-garnet laser source; 15 patients were treated with RFA, using an expandable needle electrode. Patients were followed up for up to 12 months. RESULTS A complete response was obtained in 87 % lesions treated with PLA and in 93 % lesions treated with RFA (p = ns). The overall local recurrence-free survival rates at 3, 6 and 12 months were comparable. However, a higher rate of recurrence was observed in the PLA group for lesions ≥ 21 mm (p = 0.0081). A postablation syndrome was documented in 13 patients (1 PLA; 12 RFA). Tumour necrosis factor-α was significantly higher in the RFA group (p < 0.05). CONCLUSIONS RFA is more effective in the treatment of HCC compared to PLA for lesions ≥ 21 mm. However, PLA should be considered a viable treatment option for HCC ≤ 20 mm, in view of the lower incidence of complications.
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Affiliation(s)
- Antonio Orlacchio
- Dipartimento di Diagnostica per Immagini, Imaging Molecolare, Radiologia Interventistica e Radioterapia, Policlinico Universitario "Tor Vergata", Viale Oxford 81, 00133, Rome, Italy,
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20
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Cirocchi R, Trastulli S, Boselli C, Montedori A, Cavaliere D, Parisi A, Noya G, Abraha I. Radiofrequency ablation in the treatment of liver metastases from colorectal cancer. Cochrane Database Syst Rev 2012; 2012:CD006317. [PMID: 22696357 PMCID: PMC11931680 DOI: 10.1002/14651858.cd006317.pub3] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is the most common malignant tumour and the third leading cause of cancer deaths in USA. For advanced CRC, the liver is the first site of metastatic disease; approximately 50 % of patients with CRC will develop liver metastases either synchronously or metachronously within 2 years after primary diagnosis. Hepatic resection (HR) is the only curative option, but only 15-20% of patients with liver metastases from CRC (CRLMs) are suitable for surgical standard treatment. In patients with unresectable CRLMs downsizing chemotherapy can improve resectability (16%). Modern systemic chemotherapy represents the only significant treatment for unresectable CRLMs. However several loco-regional treatments have been developed: hepatic arterial infusion (HAI), cryosurgical ablation (CSA), radiofrequency ablation (RFA), microwave ablation and selective internal radion treatment (SIRT). During the past decade RFA has superseded other ablative therapies, due to its low morbidity, mortality, safety and patient acceptability. OBJECTIVES The objective of this study was to systematically review the role of radiofrequency ablation (RFA) in the treatment of CRLMs. SEARCH METHODS We performed electronic searches in the following databases:CENTRAL, MEDLINE and EMBASE. Current trials were identified through the Internet using the Clinical-Trials.gov site (to January 2, 2012) and ASCO Proceedings. The reference lists of identified trials were reviewed for additional studies. SELECTION CRITERIA Randomized clinical trials (RCTs), quasi-randomised or controlled clinical trials (CCTs) comparing RFA to any other therapy for CRLMs were included. Observational study designs including comparative cohort studies comparing RFA to another intervention, single arm cohort studies or case control studies have been included if they have: prospectively collected data, ten or more patients; and have a mean or median follow-up time of 24 months. Patients with CRLMs who have no contraindications for RFA. Patients with unresectable extra-hepatic disease were also included.Trials have been considered regardless of language of origin. DATA COLLECTION AND ANALYSIS A total of 1144 records were identified through the above electronic searching. We included 18 studies: 10 observational studies, 7 Clinical Controlled Trials (CCTs) and an additional 1 Randomized Clinical Trial (RCT) (abstract) identified by hand searching in the 2010 ASCO Annual Meeting. The most appropriate way of summarizing time-to-event data is to use methods of survival analysis and express the intervention effect as a hazard ratio. In the included studies these outcome are mostly reported as dichotomous data so we should have asked authors research data for each participant and perform Individual Patient Data (IPD) meta-analysis. Given the study design and low quality of included studies we decided to give up and not to summarize these data. MAIN RESULTS Seventeen studies were not randomised and this increases the potential for selection bias. In addition, there was imbalance in the baseline characteristics of the participants included in all studies. All studies were classified as having a elevate risk of bias. The assessment of methodological quality of all non-randomized studies included in meta-analysis performed by the STROBE checklist has allowed us to identify several methodological limits in most of the analysed studies. At present, the information from the single RCT included (Ruers 2010) comes from an abstract of 2010 ASCO Annual Meeting where the allocation concealment was not reported; however in original protocol allocation concealment was adequately reported (EORTC 40004 protocol). The heterogeneity regarding interventions, comparisons and outcomes rendered the data not suitable. AUTHORS' CONCLUSIONS This systematic review gathers information from several controlled clinical trials and observational studies which are vulnerable to different types of bias. The imbalance between characteristics of patients in the allocated groups appears to be the main concern. Only one randomised clinical trial (published as an abstract), comparing 60 patients receiving RFA plus CT versus 59 patients receiving CT alone, was identified. This study showed that PFS was significantly higher in the group that received RFA. However, it was not able to provide information on overall survival. In conclusion, evidence from the included studies are insufficient to recommend RFA for a radical oncological treatment of CRLMs.
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Affiliation(s)
- Roberto Cirocchi
- Department of General Surgery, University of Perugia, Terni, Italy.
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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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More than just tumor destruction: immunomodulation by thermal ablation of cancer. Clin Dev Immunol 2011; 2011:160250. [PMID: 22242035 PMCID: PMC3254009 DOI: 10.1155/2011/160250] [Citation(s) in RCA: 156] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Accepted: 08/25/2011] [Indexed: 02/07/2023]
Abstract
Over the past decades, thermoablative techniques for the therapy of localized tumors have gained importance in the treatment of patients not eligible for surgical resection. Anecdotal reports have described spontaneous distant tumor regression after thermal ablation, indicating a possible involvement of the immune system, hence an induction of antitumor immunity after thermoinduced therapy. In recent years, a growing body of evidence for modulation of both adaptive and innate immunity, as well as for the induction of danger signals through thermoablation, has emerged. Induced immune responses, however, are mostly weak and not sufficient for the complete eradication of established tumors or durable prevention of disease progression, and combination therapies with immunomodulating drugs are being evaluated with promising results. This article aims to summarize published findings on immune modulation through radiofrequency ablation, cryoablation, microwave ablation therapy, high-intensity focused ultrasound, and laser-induced thermotherapy.
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23
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The effects of radiofrequency ablation on the hepatic parenchyma: Histological bases for tumor recurrences. Surg Oncol 2011; 20:237-45. [DOI: 10.1016/j.suronc.2010.01.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2009] [Revised: 01/26/2010] [Accepted: 01/27/2010] [Indexed: 01/22/2023]
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Ypsilantis P, Lambropoulou M, Anagnostopoulos C, Tsigalou C, Vasiliadis C, Kortsaris A, Papadopoulos N, Simopoulos C. Pringle maneuver exacerbates systemic inflammatory response and multiple-organ injury induced by extended liver radiofrequency ablation. Hum Exp Toxicol 2011; 30:1855-64. [PMID: 21382910 DOI: 10.1177/0960327111401438] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
AIM To assess the systemic inflammatory response (SIR) and the multi-organ damage after large-volume liver radiofrequency ablation (RFA) with or without concurrent Pringle maneuver. METHODS Wistar rats were subjected to 30% liver RFA (group RFA), liver RFA under 30-min Pringle maneuver (group RFA + P), Pringle only (group P) or sham operation (group S). Serum levels of interleukin-1α (IL-1α), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), serum biochemical profile, multiple-organ pathology and the activity of nuclear factor-κB (NF-κB) in the liver were assessed post-operatively. RESULTS The levels of IL-6 and TNF-α were increased from 1h up to 1w and 6h, respectively, in both RFA groups, while IL-6 was only mildly increased at 3 h in group P. IL-6 was higher in group RFA + P compared to group RFA. Serum biochemical profile was altered more intensely in group RFA + P compared to RFA. There was tissue injury in the non-ablated liver portion as well as in adjacent and remote organs with lesions being more severe in group RFA + P. At 1 h, NF-κB was equally activated in all study groups. CONCLUSIONS Extended liver RFA causes SIR and multi-organ injury, which are exacerbated when a concurrent Pringle maneuver is applied.
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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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Abstract
BACKGROUND Intraoperative radiofrequency ablation (IRFA) of liver metastases can be used to treat patients with complex tumours that are unsuitable for parenchymal resection alone. This systematic review assesses the frequency, patterns and severity of complications associated with this procedure. METHODS We carried out a bibliographic search on MEDLINE focused on IRFA for liver metastases, excluding hepatocarcinomas, and on intraoperative use, excluding percutaneous application. RESULTS Thirty papers published between 1999 and 2007 were analysed. They covered a total of 2822 patients and 1755 IRFA procedures. The indications and techniques for IRFA differ from those for percutaneous treatment, as do associated results and complications. Specific complications associated with IRFA, such as liver abscesses, biliary stenoses and vascular thromboses, are directly correlated with the indications and associated procedures. Published results should be interpreted with caution as IRFA can be used alone or combined with parenchymal resection. CONCLUSIONS Specific complications related to IRFA are rare, especially for lesions of <35 mm in size located far from a main biliary duct, when additional septic procedures are not used. A lesion-by-lesion approach based on the benefit : risk ratio should therefore be used in the process of making surgical decisions. Combining resection with IRFA leads to higher morbidity, especially in difficult patients with numerous bilateral lesions, but may be necessary to achieve R0 (microscopically negative margins) outcomes.
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Affiliation(s)
| | - Milène Isambert
- Digestive Tumours Unit, Institute Bergonie (Institut Bergonié)Bordeaux, France,Faculty of Medicine, University of BordeauxBordeaux, France
| | - Serge Evrard
- Digestive Tumours Unit, Institute Bergonie (Institut Bergonié)Bordeaux, France,Faculty of Medicine, University of BordeauxBordeaux, France
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Schälte G, Henzler D, Waning C, Tacke J, Rossaint R, Mahnken AH. Case study of hepatic radiofrequency ablation causing a systemic inflammatory response under total intravenous anesthesia. Korean J Radiol 2010; 11:640-7. [PMID: 21076590 PMCID: PMC2974226 DOI: 10.3348/kjr.2010.11.6.640] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2010] [Accepted: 08/06/2010] [Indexed: 01/03/2023] Open
Abstract
Objective To investigate the effects of hepatic radiofrequency ablation (RFA) in patients with malignant liver disease with respect to inflammation activation and stress response. Materials and Methods In an observational trial, we investigated the physiologic parameters of 17 patients (20 interventions) who underwent percutaneous RFA under general anesthesia after applying total intravenous anesthesia. TNFα, IL-6, IL-8, IL-10, adrenaline and noradrenaline, liver enzymes, lactate and creatine kinase were determined pre-interventionally after induction of anesthesia (T1), 90 minutes after initiation of RFA (T2), immediately after the conclusion of the procedure (T3), and 24 hours after the procedure (T4). Results A significant increase in body temperature (p < 0.001), and mean arterial pressure (p = 0.001) were measured intraoperatively (T2) and the day after the procedure (T4). Increased levels of IL-6 were measured at T3 and T4 (p = 0.001). IL-10 increased immediately after the procedure (T3; p = 0.007). IL-6 levels correlated well with the total energy applied (r = 0.837). Significant increases in the levels of adrenaline and noradrenaline were present at T3 and T4 (p < 0.001). The RFA-induced destruction of hepatic tissue was associated with increased levels of AST, ALT, GLDH and LDH. Conclusion Percutaneous RFA of hepatic malignancies causes an inflammatory and endocrine activation, similar to the systemic inflammatory response syndrome. These effects have to be taken in account when dealing with patients susceptible to sepsis or multi-organ failure.
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Affiliation(s)
- Gereon Schälte
- Department of Anesthesiology, University Hospital, RWTH Aachen, Aachen, Germany
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Zhang XX, Zhang BY, Wu LQ, Sun CD. Protective effects of magnesium isoglycyrrhizinate on liver function in patients after liver resection. Shijie Huaren Xiaohua Zazhi 2010; 18:189-194. [DOI: 10.11569/wcjd.v18.i2.189] [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 protective effects of magnesium isoglycyrrhizinate on liver function in patients after liver resection.
METHODS: Sixty-four patients undergoing liver resection were randomly divided into experimental group and control group. The experimental group was given magnesium isoglycyrrhizinate 150 mg at the beginning of the operation and postoperatively for 7 days, while the control group was not given the drug. The fasting ALT, AST, TBIL, DBIL, GGT and ALP levels were determined before operation and on days 1, 3 and 7 after operation.
RESULTS: Postoperative ALT and AST (except on day 3) levels in the experimental group were significantly lower than those in the control group (P < 0.05 or 0.01). On day 7 after operation, serum ALT levels returned to normal in 20 patients (64.5%) in the experimental group. Adverse reactions such as pseudohyperaldosteronism did not occur during the treatment course.
CONCLUSION: Magnesium isoglycyrrhizinate can inhibit the rapid increase in the levels of liver enzymes, particularly serum transaminase, and reduce complications in patients after hepatectomy, and is therefore suitable for perioperative use in these patients.
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Fietta AM, Morosini M, Passadore I, Cascina A, Draghi P, Dore R, Rossi S, Pozzi E, Meloni F. Systemic inflammatory response and downmodulation of peripheral CD25+Foxp3+ T-regulatory cells in patients undergoing radiofrequency thermal ablation for lung cancer. Hum Immunol 2009; 70:477-86. [PMID: 19332094 DOI: 10.1016/j.humimm.2009.03.012] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2009] [Revised: 03/02/2009] [Accepted: 03/24/2009] [Indexed: 01/22/2023]
Abstract
Radiofrequency thermal ablation (RFTA) is a local tumor-destructing technique that can potentially modulate the host immune response through mechanisms that are not clearly defined. We assessed whether RFTA could affect multiple systemic inflammatory and immunological parameters, including CD25+Foxp+ cells, in patients with primary or metastatic lung tumors. Three days after RFTA, a moderate and temporary systemic inflammatory response developed, as demonstrated by the increase in peripheral neutrophils and monocytes and in plasma levels of proinflammatory chemokines (MIP-1alpha, MIP-1beta, eotaxin, and interleukin[IL]-8) and acute phase reactants (complement C3 and C4, serum amyloid, alpha1 antichymotrypsin, and C-reactive protein). Moreover, we found a concomitant release of the anti-inflammatory factor IL-10. Thirty days after RFTA, a significant reduction in CD25+Foxp3+ counts with an increase in CD4+ T-cell proliferation and number of interferon-gamma-secreting cells was observed. The reduction in CD25+Foxp3+ cells lasted up to 90 days after treatment. The use of RFTA in lung cancer patients has an immunomodulatory activity: it induces a self-limiting systemic inflammation early and later a reduction of circulating CD25+Foxp3+ Tregs. In addition to tumor ablation, downmodulation of this regulatory subset might be an important mechanism involved in the long-term clinical efficacy of RFTA.
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Affiliation(s)
- Anna Maria Fietta
- Department of Hematological, Pneumological, and Cardiovascular Sciences, Section of Pneumology, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
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Kasahara K, Yajima Y, Ikeda C, Kamiyama I, Takaki T, Kakizawa T, Shibahara T. Systemic Inflammatory Response Syndrome and Postoperative Complications after Orthognathic Surgery. THE BULLETIN OF TOKYO DENTAL COLLEGE 2009; 50:41-50. [DOI: 10.2209/tdcpublication.50.41] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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