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Wang F, Lu J, Yang T, Ren Y, Ratti F, Marques HP, Silva S, Soubrane O, Lam V, Poultsides GA, Popescu I, Grigorie R, Alexandrescu S, Martel G, Workneh A, Guglielmi A, Hugh T, Aldrighetti L, Endo I, Lv Y, Zhang XF, Pawlik TM. Perioperative Changes in Serum Transaminase Levels: Impact on Postoperative Morbidity After Liver Resection of Hepatocellular Carcinoma. Ann Surg 2025; 281:624-631. [PMID: 38348655 DOI: 10.1097/sla.0000000000006235] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2025]
Abstract
OBJECTIVES To define how dynamic changes in pre versus postoperative serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels may impact postoperative morbidity after curative-intent resection of hepatocellular carcinoma (HCC). BACKGROUND Hepatic ischemia/reperfusion can occur at the time of liver resection and may be associated with adverse outcomes after liver resection. METHODS Patients who underwent curative resection for HCC between 2010 and 2020 were identified from an international multi-institutional database. Changes in AST and ALT (CAA) on postoperative day 3 versus preoperative values ( ) were calculated using the formula: based on a fusion index through the Euclidean norm, which was examined relative to the Comprehensive Complication Index (CCI). The impact of CAA on CCI was assessed by the restricted cubic spline regression and Random Forest analyses. RESULTS A total of 759 patients were included in the analytic cohort. Median CAA was 1.7 (range: 0.9-3.25); 431 (56.8%) patients had a CAA <2 215 (28.3%) patients with CAA 2 to 5, and 113 (14.9%) patients had CAA ≥5. The incidence of postoperative complications was 65.0% (n = 493) with a median CCI of 20.9 (interquartile range: 20.9-33.5). Spline regression analysis demonstrated a nonlinear incremental association between CAA and CCI. The optimal cutoff value of CAA was 5, identified by the recursive partitioning technique. After adjusting for other competing risk factors, CAA ≥5 remained strongly associated with the risk of postoperative complications (reference CAA <5, odds ratio: 1.63, 95% CI: 1.05-2.55, P = 0.03). In fact, the use of CAA to predict postoperative complications was very good in both the derivative (area under the curve: 0.88) and external (area under curve: 0.86) cohorts (n = 1137). CONCLUSIONS CAA was an independent predictor of CCI after liver resection for HCC. The use of routine laboratories, such as AST and ALT, can help identify patients at the highest risk of postoperative complications after HCC resection.
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Affiliation(s)
- Fumin Wang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- School of Future Technology, Xi'an Jiaotong University, Xi'an, PR China
| | - Jingming Lu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- School of Future Technology, Xi'an Jiaotong University, Xi'an, PR China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai, China
| | - Yaoxing Ren
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- School of Future Technology, Xi'an Jiaotong University, Xi'an, PR China
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Silvia Silva
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Olivier Soubrane
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, Australia
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Razvan Grigorie
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Aklile Workneh
- Department of Surgery, University of Ottawa, Ottawa, Canada
| | | | - Tom Hugh
- Department of Surgery, The University of Sydney, School of Medicine, Sydney, Australia
| | | | - Itaru Endo
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Yi Lv
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- School of Future Technology, Xi'an Jiaotong University, Xi'an, PR China
| | - Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- School of Future Technology, Xi'an Jiaotong University, Xi'an, PR China
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
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Chen Q, Fu Y, Li Y, Cai H, Wang X, Wu Z, Meng L, Zhang M, Chen Z, Jiang J, Cheng K, Li J, Zhang D, Cai Y, You J, Cai Y, Peng B. Interim analysis of short-term outcomes after laparoscopic spleen-preserving distal pancreatectomy with or without preservation of splenic vessels: a randomised controlled trial. Int J Surg 2025; 111:617-627. [PMID: 38954668 PMCID: PMC11745598 DOI: 10.1097/js9.0000000000001874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 06/17/2024] [Indexed: 07/04/2024]
Abstract
BACKGROUND Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) is a widely adopted surgical approach for benign and low-grade malignant neoplasms of the distal pancreas. The Kimura and Warshaw techniques represent two principal strategies, yet it still needs to be determined which one is superior. Our investigation aimed to evaluate the clinical outcomes associated with each technique. MATERIALS AND METHODS This single-center, parallel-group, patient-blinded randomized controlled trial was conducted at the West China Hospital of Sichuan University. Stratified block randomization was utilized to enroll 114 patients starting in March 2022, with an interim analysis of short-term outcomes scheduled after 45-50% of participant enrollment. Patients were randomized to receive LSPDP via either the Kimura or Warshaw technique. The primary endpoint was intraoperative blood loss, while secondary endpoints included a range of outcomes from composite outcome to quality of life, as quantified by the EQ-5D-5L. RESULTS From March 2022 to November 2023, 53 patients were randomly allocated to the Kimura ( n =25) or Warshaw ( n =28) groups for LSPDP. Baseline characteristics and postoperative outcomes were similar between the groups, such as pancreatic fistula incidence, EQ-5D-5L index scores, and delayed gastric emptying rates. Per-protocol (PP) analysis revealed that the Kimura group experienced significantly less blood loss (52.5±51.6 ml vs. 91.7±113.5 ml, P =0.007) and a reduced rate of composite outcome (23.8 vs. 56.7%, P =0.019), but incurred higher costs in the Warshaw group (¥56 227.4±¥7027.0 vs. ¥63 513.8±¥12 944.5, P =0.013). Splenic infarction rates were higher in the Warshaw group, though not statistically significant (ITT: 39.3 vs. 12.5%, P =0.058; PP: 36.7 vs. 14.3%, P =0.113), without necessitating intervention. Neither group experienced postpancreatectomy hemorrhage, 90-day mortality, or ICU admissions, and all postoperative complications were mild (Clavien-Dindo Grade CONCLUSIONS The 90-day interim analysis postoperatively indicates that both Kimura and Warshaw techniques for LSPDP are safe and viable. The Kimura technique, however, confers superior in terms of reduced intraoperative blood loss and fewer complications, alongside lower costs.
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Affiliation(s)
- Qiangxing Chen
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
- West China School of Medicine, West China Hospital, Sichuan University
- Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yangzhi Fu
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
- West China School of Medicine, West China Hospital, Sichuan University
| | - Yongbin Li
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
- Department of Hepatopancreatobiliary Minimal Invasive Surgery, Shangjin Nanfu Hospital
| | - He Cai
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
| | - Xin Wang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
| | - Zhong Wu
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
| | - Lingwei Meng
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
- West China School of Medicine, West China Hospital, Sichuan University
| | - Man Zhang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
| | - Zixin Chen
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
- West China School of Medicine, West China Hospital, Sichuan University
| | - Jingwen Jiang
- Division of Pancreatic Surgery and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China; and Med-X Center for Informatics, Sichuan University
| | - Ke Cheng
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
- Division of Liver Surgery, Department of General Surgery, West China Hospital of Sichuan University
| | - Jun Li
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
- West China School of Medicine, West China Hospital, Sichuan University
| | - Dian Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Guangzhou, China
| | - Yu Cai
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
| | - Jiaying You
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
| | - Yunqiang Cai
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
| | - Bing Peng
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University
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Burda R, Křemen R, Némethová M, Burda J. Clinical usage of ischemic tolerance-where are its limits? Asian J Surg 2024; 47:4674-4680. [PMID: 38824026 DOI: 10.1016/j.asjsur.2024.05.167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 05/24/2024] [Indexed: 06/03/2024] Open
Abstract
Ischemic tolerance is a robust internal defense mechanism of all living organisms. The effectiveness of this mechanism has been repeatedly demonstrated in experiments, but a comprehensive review of the clinical applicability of this phenomenon in practice has not yet been published. The results in clinical practice sound ambiguous and unconvincing in comparison with the results of experimental studies. Also, in many localities, the effect of ischemic tolerance was not clinically proven. For the reasons mentioned, the authors analyze the possible causes of the mentioned discrepancies and provide a comprehensive insight into the possible relevant clinical use of this phenomenon in practice for different groups of patients.
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Affiliation(s)
- Rastislav Burda
- Department of Trauma Surgery, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Rastislavova 43, 040 01, Košice, Slovakia; Department of Trauma Surgery, Louis Pasteur University Hospital, Rastislavova 43, 040 01, Košice, Slovakia.
| | - Róbert Křemen
- Department of Trauma Surgery, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Rastislavova 43, 040 01, Košice, Slovakia; Department of Trauma Surgery, Louis Pasteur University Hospital, Rastislavova 43, 040 01, Košice, Slovakia
| | - Miroslava Némethová
- Institute of Neurobiology of Biomedical Research Center, Slovak Academy of Sciences, 040 01, Košice, Slovakia
| | - Jozef Burda
- Institute of Neurobiology of Biomedical Research Center, Slovak Academy of Sciences, 040 01, Košice, Slovakia
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Bekheit M, Grundy L, Salih AK, Bucur P, Vibert E, Ghazanfar M. Post-hepatectomy liver failure: A timeline centered review. Hepatobiliary Pancreat Dis Int 2023; 22:554-569. [PMID: 36973111 DOI: 10.1016/j.hbpd.2023.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 03/10/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Post-hepatectomy liver failure (PHLF) is a leading cause of postoperative mortality after liver surgery. Due to its significant impact, it is imperative to understand the risk stratification and preventative strategies for PHLF. The main objective of this review is to highlight the role of these strategies in a timeline centered way around curative resection. DATA SOURCES This review includes studies on both humans and animals, where they addressed PHLF. A literature search was conducted across the Cochrane Library, Embase, MEDLINE/PubMed, and Web of Knowledge electronic databases for English language studies published between July 1997 and June 2020. Studies presented in other languages were equally considered. The quality of included publications was assessed using Downs and Black's checklist. The results were presented in qualitative summaries owing to the lack of studies qualifying for quantitative analysis. RESULTS This systematic review with 245 studies, provides insight into the current prediction, prevention, diagnosis, and management options for PHLF. This review highlighted that liver volume manipulation is the most frequently studied preventive measure against PHLF in clinical practice, with modest improvement in the treatment strategies over the past decade. CONCLUSIONS Remnant liver volume manipulation is the most consistent preventive measure against PHLF.
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Affiliation(s)
- Mohamed Bekheit
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK; Institute of Medical Sciences, Medical School, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK; Hépatica, Integrated Center of HPB Care, Elite Hospital, Agriculture Road, Alexandria, Egypt.
| | - Lisa Grundy
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK
| | - Ahmed Ka Salih
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK; Institute of Medical Sciences, Medical School, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK
| | - Petru Bucur
- Department of Surgery, University Hospital Tours, Val de la Loire 37000, France
| | - Eric Vibert
- Centre Hépatobiliaire, Paul Brousse Hospital, 12 Paul Valliant Couturier, 94804 Villejuif, France
| | - Mudassar Ghazanfar
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK
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Huang Y, Xu L, Wang N, Wei Y, Wang W, Xu M, Jiang L. Preoperative dexamethasone administration in hepatectomy of 25-min intermittent Pringle's maneuver for hepatocellular carcinoma: a randomized controlled trial. Int J Surg 2023; 109:3354-3364. [PMID: 37526089 PMCID: PMC10651268 DOI: 10.1097/js9.0000000000000622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/11/2023] [Indexed: 08/02/2023]
Abstract
BACKGROUND A previous randomized controlled trial demonstrated that intermittent Pringle's maneuver (IPM) with a 25-min ischemic interval could be applied safely and efficiently in hepatectomy for patients with hepatocellular carcinoma (HCC). But prolonging the hepatic inflow clamping time will inevitably aggravate the ischemia-reperfusion injury. Therefore, we aimed to evaluate the effect of prophylactic dexamethasone on alleviating surgical stress for HCC patients with a 25-min ischemic interval. METHODS From December 2022 to April 2023, patients who met the inclusion criteria were randomly assigned to the dexamethasone group or control group. Perioperative data and short-term survival outcomes between the two groups were recorded and compared, and subgroup analysis was performed. RESULTS Two hundred and seventy patients were allocated to the dexamethasone group ( n =135) and control group ( n =135). Patients in the dexamethasone group had lower area under the curve of serial alanine aminotransferase (AUC ALT ) ( P =0.043) and aspartate aminotransferase (AUC AST ) ( P =0.009), total bilirubin (TB) ( P =0.018), procalcitonin (PCT) ( P =0.012), interleukin-6 (IL-6) ( P =0.006), incidence of major complication ( P =0.031) and shorter postoperative hospital stay ( P =0.046) than those in the control group. Subgroup analysis showed that the dexamethasone group experienced milder hepatocellular injury than the control group for patients with cirrhosis, and for patients without cirrhosis, the dexamethasone group experienced milder inflammatory response. Moreover, the dexamethasone group preserved better liver function and experienced milder inflammatory response for patients undergoing major hepatectomy, although the hepatocellular injury was not significantly improved. CONCLUSION Preoperative dexamethasone administration can help improve perioperative outcomes for HCC patients when applying IPM with a 25-min ischemic interval in hepatectomy.
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Affiliation(s)
| | | | | | | | | | - Mingqing Xu
- Department of General Surgery, Division of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Li Jiang
- Department of General Surgery, Division of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
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de Oliveira GC, de Oliveira WK, Yoshida WB, Sobreira ML. Impacts of ischemic preconditioning in liver resection: systematic review with meta-analysis. Int J Surg 2023; 109:1720-1727. [PMID: 36913265 PMCID: PMC10389598 DOI: 10.1097/js9.0000000000000243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 01/19/2023] [Indexed: 03/14/2023]
Abstract
OBJECTIVE To assess the beneficial effects of ischemic preconditioning (IPC) in liver resection and evaluate its applicability in clinical practice. SUMMARY BACKGROUND DATA Liver surgeries are usually associated with intentional transient ischemia for hemostatic control. IPC is a surgical step that intends to reduce the effects of ischemia-reperfusion; however, there is no strong evidence about the real impact of the IPC, and it is necessary to effectively clarify what its effects are. METHODS Randomized clinical trials were selected, comparing IPC with no preconditioning in patients undergoing liver resection. Data were extracted by three independent researchers according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, Supplemental Digital Content 1, http://links.lww.com/JS9/A79 . Several outcomes were evaluated, including postoperative peaks of transaminases and bilirubin, mortality, length of hospital stay, length of stay in the ICU, bleeding, and transfusion of blood products, among others. Bias risks were assessed using the Cochrane collaboration tool. RESULTS Seventeen articles were selected, with a total of 1052 patients. IPC did not change the surgical time of the liver resections while these patients bled less (Mean Difference: -49.97 ml; 95% CI: -86.32 to -13.6; I2 : 64%), needed less blood products [relative risk (RR): 0.71; 95% CI: 0.53-0.96; I2 =0%], and had a lower risk of postoperative ascites (RR: 0.40; 95% CI: 0.17-0.93; I2 =0%). The other outcomes had no statistical differences or could not have their meta-analyses conducted due to high heterogeneity. CONCLUSIONS IPC is applicable in clinical practice, and it has some beneficial effects. However, there is not enough evidence to encourage its routine use.
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Affiliation(s)
- Glauber C. de Oliveira
- Department of Surgery and Orthopedics, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
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Benoit L, Dieu A, Foguenne M, Bonaccorsi-Riani E. Experimental and Clinical Aspects of Sevoflurane Preconditioning and Postconditioning to Alleviate Hepatic Ischemia-Reperfusion Injury: A Scoping Review. Int J Mol Sci 2023; 24:2340. [PMID: 36768670 PMCID: PMC9916998 DOI: 10.3390/ijms24032340] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/21/2022] [Accepted: 01/22/2023] [Indexed: 01/27/2023] Open
Abstract
Ischemia-reperfusion injury (IRI) is an inflammatory process inherent in organ transplantation procedures. It is associated with tissue damage and, depending on its intensity, can impact early graft function. In liver transplantation (LT), strategies to alleviate IRI are essential in order to increase the use of extended criteria donor (ECD) grafts, which are more susceptible to IRI, as well as to improve postoperative graft and patient outcomes. Sevoflurane, a commonly used volatile anesthetic, has been shown to reduce IRI. This scoping review aims to give a comprehensive overview of the existing experimental and clinical data regarding the potential benefits of sevoflurane for hepatic IRI (HIRI) and to identify any gaps in knowledge to guide further research. We searched Medline and Embase for relevant articles. A total of 380 articles were identified, 45 of which were included in this review. In most experimental studies, the use of sevoflurane was associated with a significant decrease in biomarkers of acute liver damage and oxidative stress. Administration of sevoflurane before hepatic ischemia (preconditioning) or after reperfusion (postconditioning) appears to be protective. However, in the clinical setting, results are conflicting. While some studies showed a reduction of postoperative markers of liver injury, the benefit of sevoflurane on clinical outcomes and graft survival remains unclear. Further prospective clinical trials remain necessary to assess the clinical relevance of the use of sevoflurane as a protective factor against HIRI.
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Affiliation(s)
- Loïc Benoit
- Department of Anesthesiology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
| | - Audrey Dieu
- Department of Anesthesiology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
| | - Maxime Foguenne
- Abdominal Transplant Unit, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
- Pôle de Chirurgie Expérimentale et Transplantation-Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium
| | - Eliano Bonaccorsi-Riani
- Abdominal Transplant Unit, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
- Pôle de Chirurgie Expérimentale et Transplantation-Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium
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Laudanski K. Quo Vadis Anesthesiologist? The Value Proposition of Future Anesthesiologists Lies in Preserving or Restoring Presurgical Health after Surgical Insult. J Clin Med 2022; 11:1135. [PMID: 35207406 PMCID: PMC8879076 DOI: 10.3390/jcm11041135] [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: 01/30/2022] [Accepted: 02/18/2022] [Indexed: 12/26/2022] Open
Abstract
This Special Issue of the Journal of Clinical Medicine is devoted to anesthesia and perioperative care [...].
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Affiliation(s)
- Krzysztof Laudanski
- Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA; ; Tel.: +1-215-662-8000
- Leonard Davis Institute for Healthcare Economics, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA
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Teodoro JS, Da Silva RT, Machado IF, Panisello-Roselló A, Roselló-Catafau J, Rolo AP, Palmeira CM. Shaping of Hepatic Ischemia/Reperfusion Events: The Crucial Role of Mitochondria. Cells 2022; 11:688. [PMID: 35203337 PMCID: PMC8870414 DOI: 10.3390/cells11040688] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/09/2022] [Accepted: 02/11/2022] [Indexed: 12/10/2022] Open
Abstract
Hepatic ischemia reperfusion injury (HIRI) is a major hurdle in many clinical scenarios, including liver resection and transplantation. Various studies and countless surgical events have led to the observation of a strong correlation between HIRI induced by liver transplantation and early allograft-dysfunction development. The detrimental impact of HIRI has driven the pursuit of new ways to alleviate its adverse effects. At the core of HIRI lies mitochondrial dysfunction. Various studies, from both animal models and in clinical settings, have clearly shown that mitochondrial function is severely hampered by HIRI and that its preservation or restoration is a key indicator of successful organ recovery. Several strategies have been thus implemented throughout the years, targeting mitochondrial function. This work briefly discusses some the most utilized approaches, ranging from surgical practices to pharmacological interventions and highlights how novel strategies can be investigated and implemented by intricately discussing the way mitochondrial function is affected by HIRI.
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Affiliation(s)
- João S. Teodoro
- MitoLab, Department of Life Sciences, University of Coimbra, 3000 Coimbra, Portugal; (J.S.T.); (A.P.R.)
- MitoLab, Mitochondria, Metabolism and Disease Group, Center for Neurosciences and Cell Biology, Faculdade de Medicina, University of Coimbra, 3000 Coimbra, Portugal; (R.T.D.S.); (I.F.M.)
- IIIUC–Institute of Interdisciplinary Research, University of Coimbra, Pólo II da Universidade de Coimbra, 3000 Coimbra, Portugal
| | - Rui T. Da Silva
- MitoLab, Mitochondria, Metabolism and Disease Group, Center for Neurosciences and Cell Biology, Faculdade de Medicina, University of Coimbra, 3000 Coimbra, Portugal; (R.T.D.S.); (I.F.M.)
- Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, Spain; (A.P.-R.); (J.R.-C.)
| | - Ivo F. Machado
- MitoLab, Mitochondria, Metabolism and Disease Group, Center for Neurosciences and Cell Biology, Faculdade de Medicina, University of Coimbra, 3000 Coimbra, Portugal; (R.T.D.S.); (I.F.M.)
- IIIUC–Institute of Interdisciplinary Research, University of Coimbra, Pólo II da Universidade de Coimbra, 3000 Coimbra, Portugal
| | - Arnau Panisello-Roselló
- Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, Spain; (A.P.-R.); (J.R.-C.)
| | - Joan Roselló-Catafau
- Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, Spain; (A.P.-R.); (J.R.-C.)
| | - Anabela P. Rolo
- MitoLab, Department of Life Sciences, University of Coimbra, 3000 Coimbra, Portugal; (J.S.T.); (A.P.R.)
- MitoLab, Mitochondria, Metabolism and Disease Group, Center for Neurosciences and Cell Biology, Faculdade de Medicina, University of Coimbra, 3000 Coimbra, Portugal; (R.T.D.S.); (I.F.M.)
| | - Carlos M. Palmeira
- MitoLab, Department of Life Sciences, University of Coimbra, 3000 Coimbra, Portugal; (J.S.T.); (A.P.R.)
- MitoLab, Mitochondria, Metabolism and Disease Group, Center for Neurosciences and Cell Biology, Faculdade de Medicina, University of Coimbra, 3000 Coimbra, Portugal; (R.T.D.S.); (I.F.M.)
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Huang Y, Liao A, Pu X, Yang J, Lv T, Yan L, Yang J, Wu H, Jiang L. A randomized controlled trial of effect of 15- or 25-minute intermittent Pringle maneuver on hepatectomy for hepatocellular carcinoma. Surgery 2021; 171:1596-1604. [PMID: 34916072 DOI: 10.1016/j.surg.2021.11.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/10/2021] [Accepted: 11/15/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND The feasibility and safety of using longer ischemic interval during intermittent Pringle maneuver for hepatectomy in patients with hepatocellular carcinoma are still unclear. The aim of this study was to compare the short-term outcomes of hepatectomy using intermittent Pringle maneuver with an ischemic interval of 25 minutes versus 15 minutes in hepatocellular carcinoma patients. METHODS A total of 344 patients with hepatocellular carcinoma undergoing hepatectomy were randomized to receive the intermittent Pringle maneuver with a 15-minute (n = 172) or 25-minute (n = 172) ischemic interval. Primary endpoint was transaminase-based postoperative hepatic injury, assessed by their peak values as well as area under the curve of the postoperative course of aminotransferases. Secondary endpoints included the intraoperative blood loss, transection speed, morbidity, mortality, and postoperative inflammatory reaction. RESULTS There were no significant differences between the 2 groups in the postoperative aminotransferase serum levels or their area under the curve values, but the 25-minute intermittent Pringle maneuver group was associated with significantly higher speed for liver transection (1.38 vs 1.23 cm2/min, P = .002) and a lower blood loss during transection (109 vs 166 mL, P < .001) than the 15-minute intermittent Pringle maneuver group. Postoperative complications, inflammatory cytokines serum levels, and 90-day mortality were comparable. Stratification analysis showed that the 25-minute intermittent Pringle maneuver did not aggravate the hepatic injury but resulted in a lower blood loss during transection and higher transection speed in hepatocellular carcinoma patient undergoing laparoscopic or open hepatectomy. CONCLUSION Intermittent Pringle maneuver with a 25-minute ischemic interval can be applied safely and efficiently in open or laparoscopic hepatectomy in patients with hepatocellular carcinoma patients.
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Affiliation(s)
- Yang Huang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Anque Liao
- Anesthesia and Operating Centre, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Xingyu Pu
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jian Yang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Tao Lv
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Lunan Yan
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jiayin Yang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Hong Wu
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Li Jiang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
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11
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Huang YQ, Wen RT, Li XT, Zhang J, Yu ZY, Feng YF. The Protective Effect of Dexmedetomidine Against Ischemia-Reperfusion Injury after Hepatectomy: A Meta-Analysis of Randomized Controlled Trials. Front Pharmacol 2021; 12:747911. [PMID: 34712138 PMCID: PMC8546301 DOI: 10.3389/fphar.2021.747911] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 09/27/2021] [Indexed: 11/24/2022] Open
Abstract
Background: Hepatic inflow occlusion proceeded to reduce blood loss during hepatectomy induces ischemia-reperfusion (IR) injury in the remnant liver. Dexmedetomidine, a selective α2-adrenoceptor agonist used as an anesthetic adjuvant, has been shown to attenuate IR injury in preclinical and clinical studies. However, a meta-analysis is needed to systematically evaluate the protective effect of perioperative dexmedetomidine use on IR injury induced by hepatectomy. Methods: A prospectively registered meta-analysis following Cochrane and PRISMA guidelines concerning perioperative dexmedetomidine use on IR injury after hepatectomy was performed via searching Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, Web of Science, CNKI, WanFang, and Sinomed for eligible randomized controlled trials up to 2021.3.31. The main outcome is postoperative liver function. Risk of bias was assessed by the Cochrane Risk of Bias tool. Review Manager 5.3 and Stata12.0 were applied to perform data analyses. Results: Eight RCTs enrolling 468 participants were included. Compared with 0.9% sodium chloride, dexmedetomidine decreased serum concentration of ALT (WMD = −66.54, 95% CI: −92.10–−40.98), AST (WMD= −82.96, 95% CI: −106.74–−59.17), TBIL (WMD = −4.51, 95% CI: −7.32–−1.71), MDA (WMD = −3.09, 95% CI: −5.17–−1.01), TNF-α (WMD = −36.54, 95% CI: −61.33–−11.95) and IL-6 (WMD = −165.05, 95% CI: −225.76–−104.34), increased SOD activity (WMD = 24.70, 95% CI: 18.09–31.30) within postoperative one day. There was no significant difference in intraoperative or postoperative recovery parameters between groups. Conclusions: Perioperative administration of dexmedetomidine can exert a protective effect on liver IR injury after hepatectomy. Additional studies are needed to further evaluate postoperative recovery outcomes of dexmedetomidine with different dosing regimens.
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Affiliation(s)
- Ya-Qun Huang
- Department of Pharmacy, Peking University People's Hospital, Beijing, China.,Department of Pharmaceutical Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
| | - Rui-Ting Wen
- Department of Pharmacy, Peking University People's Hospital, Beijing, China.,Department of Pharmaceutical Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
| | - Xiao-Tong Li
- Department of Pharmacy, Peking University Third Hospital, Beijing, China
| | - Jiao Zhang
- Department of Pharmacy, Peking University People's Hospital, Beijing, China.,Department of Pharmaceutical Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
| | - Zhi-Ying Yu
- Department of Pharmacy, Peking University People's Hospital, Beijing, China
| | - Yu-Fei Feng
- Department of Pharmacy, Peking University People's Hospital, Beijing, China
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12
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Yoshino K, Hamzaoui Y, Yoh T, Ftériche FS, Aussilhou B, Beaufrère A, Belghiti J, Soubrane O, Cauchy F, Dokmak S. Liver resection for octogenarians in a French center: prolonged hepatic pedicle occlusion and male sex increase major complications. Langenbecks Arch Surg 2021; 406:1543-1552. [PMID: 34057599 DOI: 10.1007/s00423-021-02210-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 05/17/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE The prolonged life expectancy and increase in aging of the population have led surgeons to propose hepatectomy in the elderly population. In this study, we evaluate the surgical outcome of octogenarians in a single French center. METHODS Between 2000 and 2020, 78 patients over 80 years old were retrospectively analyzed. The risk factors of major complications (Clavien-Dindo ≥ grade IIIa) and patient performance after surgery by using textbook outcome (TO) (no surgical complications, no prolonged hospital stay (≤ 15 days), no readmission ≤90 days after discharge, and no mortality ≤90 days after surgery) were studied. RESULTS The main surgical indication was for malignancy (96%), including mainly colorectal liver metastases (n = 41; 53%) and hepatocellular carcinoma (n = 22; 28%), and major hepatectomy was performed in 28 patients (36%). There were 6 (8%) postoperative mortalities. The most frequent complications were pulmonary (n = 22; 32%), followed by renal insufficiency (n = 22; 28%) and delirium (n = 16; 21%). Major complications occurred in 19 (24%) patients. On multivariate analysis, the main risk factors for major complications were the median vascular clamping time (0 vs 35; P = 0.04) and male sex (P = 0.046). TO was ultimately achieved in 30 patients (38%), and there was no prognostic factor for achievement of TO. CONCLUSIONS Hepatectomy in octogenarians is associated with acceptable morbidity and mortality. Meanwhile, prolonged hepatic pedicle clamping should be avoided especially if hepatectomy is planned in a male patient.
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Affiliation(s)
- Kenji Yoshino
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, University of Paris, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92100, Clichy, France
| | - Yanis Hamzaoui
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, University of Paris, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92100, Clichy, France
| | - Tomoaki Yoh
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, University of Paris, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92100, Clichy, France
| | - Fadhel Samir Ftériche
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, University of Paris, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92100, Clichy, France
| | - Béatrice Aussilhou
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, University of Paris, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92100, Clichy, France
| | - Aurélie Beaufrère
- Department of Pathology, University of Paris, Hôpital Beaujon, AP-HP, Clichy, France
| | - Jacques Belghiti
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, University of Paris, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92100, Clichy, France
| | - Olivier Soubrane
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, University of Paris, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92100, Clichy, France
| | - François Cauchy
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, University of Paris, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92100, Clichy, France
| | - Safi Dokmak
- Department of HPB Surgery and Liver Transplantation, DMU DIGEST, University of Paris, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92100, Clichy, France.
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13
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Stankiewicz R, Grąt M. Direct, remote and combined ischemic conditioning in liver surgery. World J Hepatol 2021; 13:533-542. [PMID: 34131468 PMCID: PMC8173344 DOI: 10.4254/wjh.v13.i5.533] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/28/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
Liver ischemia-reperfusion injury is a major cause of postoperative liver dysfunction, morbidity and mortality following liver resection and transplantation. Ischemic conditioning has been shown to ameliorate ischemia-reperfusion injury in small animal models. It can be applied directly or remotely when cycles of ischemia and reperfusion are applied to a distant site or organ. Considering timing of the procedure, different protocols are available. Ischemic preconditioning refers to that performed before the duration of ischemia of the target organ. Ischemic perconditioning is performed over the duration of ischemia of the target organ. Ischemic postconditioning applies brief episodes of ischemia at the onset of reperfusion following a prolonged ischemia. Animal studies pointed towards suppressing cytokine release, enhancing the production of hepatoprotective adenosine and reducing liver apoptotic response as the potential mechanisms responsible for the protective effect of direct tissue conditioning. Interactions between neural, humoral and systemic pathways all lead to the protective effect of remote ischemic preconditioning. Despite promising animal studies, none of the aforementioned protocols proved to be clinically effective in liver surgery with the exception of morbidity reduction in cirrhotic patients undergoing liver resection. Further human clinical trials with application of novel conditioning protocols and combination of methods are warranted before implementation of ischemic conditioning in day-to-day clinical practice.
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Affiliation(s)
- Rafał Stankiewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw 02-097, Poland.
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw 02-097, Poland
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14
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Kim D, Choi JW, Han S, Gwak MS, Kim GS, Jeon SY, Ryu S, Hahm TS, Ko JS. Ischemic Preconditioning Protects Against Hepatic Ischemia-Reperfusion Injury Under Propofol Anesthesia in Rats. Transplant Proc 2020; 52:2964-2969. [PMID: 32586662 DOI: 10.1016/j.transproceed.2020.05.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 02/19/2020] [Accepted: 05/12/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND Propofol is widely used in general anesthesia, and it has been reported to protect various organs against ischemia-reperfusion injury (IRI), including liver. To evaluate the hepatoprotective effects of ischemic preconditioning (IP) under propofol anesthesia, we investigated the possible underlying mechanisms in rats. METHODS Male Sprague-Dawley rats were randomly assigned to 3 groups: sham group (n = 5), non-IP group (n = 9; 45 minutes of hepatic ischemia followed by 2 hours of reperfusion), and IP group (n = 9; IP applied as 10 minutes of hepatic ischemia followed by 15 minutes of reperfusion before 45 minutes of ischemia). Anesthesia was maintained with intravenous (IV) infusion of propofol (800 μg/kg/min). Liver enzymes, histopathological changes, and cytokine expression were examined. RESULTS The IP group showed significantly lower liver enzyme levels (aspartate aminotransferase, P = .045; alanine aminotransferase, P = .006) and reduced the histologic grades of hepatic injury 2 hours after reperfusion (P = .004) compared to the non-IP group. Lactate dehydrogenase activity (P < .001) and interleukin-6 mRNA levels were significantly higher in the non-IP group than in the sham and IP groups (P = .002, both groups). CONCLUSIONS Our results demonstrate that IP under propofol anesthesia significantly attenuated hepatic IRI. The principal mechanism of the protective effects appeared to involve reduced expression of the IL-6 pro-inflammatory cytokine and subsequent reduction of the degree of necrosis.
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Affiliation(s)
- Doyeon Kim
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Won Choi
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sangbin Han
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi Sook Gwak
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gaab Soo Kim
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Su Yeon Jeon
- Department of Laboratory Animal Research, Samsung Biomedical Research Institute, Seoul, Korea
| | - Sun Ryu
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Soo Hahm
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Justin Sangwook Ko
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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15
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Vetrugno L, Bove T. Ischemic preconditioning: light and shadow. Minerva Anestesiol 2020; 86:241-243. [PMID: 32013338 DOI: 10.23736/s0375-9393.20.14344-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Luigi Vetrugno
- Department of Medicine, Anesthesia and Intensive Care Clinic, University of Udine, Udine, Italy -
- Department of Anesthesia and Intensive Care, University Hospital of Udine, Udine, Italy -
| | - Tiziana Bove
- Department of Medicine, Anesthesia and Intensive Care Clinic, University of Udine, Udine, Italy
- Department of Anesthesia and Intensive Care, University Hospital of Udine, Udine, Italy
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16
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Ke J, Liu F, Liu Y. Glissonean Pedicle Transection with Hepatic Vein Exclusion for Hepatocellular Carcinoma: A Comparative Study with the Pringle Maneuver. J Laparoendosc Adv Surg Tech A 2020; 30:58-63. [PMID: 31573392 DOI: 10.1089/lap.2019.0484] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background: Appropriate surgical techniques to control hemorrhage and retain residual liver function are key to treatment success for hepatocellular carcinoma (HCC). This study aimed to evaluate the clinical application of Glissonean pedicle transection with hepatic vein exclusion (HVE). Materials and Methods: Between April 2013 and December 2015, 50 patients underwent surgical resection for HCC and were randomly allocated to receive Glissonean pedicle transection with HVE (Glisson group, n = 25) or Pringle maneuver with intermittent clamping (Pringle group, n = 25). Intraoperative blood loss, blood transfusion, operation time, positive surgical margins, complications (bile leakage, hemorrhage, and ascites), and hospital stay were compared between groups, along with the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) levels at baseline and postoperative days 1, 3, and 7. Results: The operation time and range of hepatic resection were comparable between groups. Although both groups had similar preoperative ALT, AST, and TB levels, these levels on postoperative days 1, 3, and 7 were significantly lower in the Glisson group than in the Pringle group (all P < .01). Compared with the Pringle group, the Glisson group had a significantly lower intraoperative blood loss (P < .001), a lower blood transfusion rate (P = .017), lower incidence rates of postoperative hemorrhage (P = .030) and ascites (P = .024), a lower positive surgical margin rate (P = .017), and a shorter length of hospital stay (P < .001). Conclusions: Glissonean pedicle transection with HVE is a safe, simple, and effective procedure for hepatic resection.
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Affiliation(s)
- Jianji Ke
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Feiqi Liu
- The Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
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17
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Zhang Y, Liu M, Yang Y, Cao J, Mi W. Dexmedetomidine exerts a protective effect on ischemia-reperfusion injury after hepatectomy: A prospective, randomized, controlled study. J Clin Anesth 2019; 61:109631. [PMID: 31669050 DOI: 10.1016/j.jclinane.2019.109631] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 08/19/2019] [Accepted: 09/27/2019] [Indexed: 02/06/2023]
Abstract
STUDY OBJECTIVE Dexmedetomidine, a highly selective α2-receptor agonist, has been widely used for protection against ischemia-reperfusion (IR) injury. We hypothesized that dexmedetomidine might exert a protective effect on IR injury after hepatectomy. DESIGN A prospective, randomized, single-blind study was conducted in 58 patients undergoing hepatectomy who were randomly assigned to two study groups. The dexmedetomidine group (D group) received a loading dose of 0.5 μg/kg for 10 min, and maintained it with 0.5 μg/kg/h until resection of the liver lobes. The control group (C group), received 0.9% sodium chloride administered in the same volume and infusion rate as D group. Eleven patients had hepatic inflow occlusion in D group as did 14 patients in C group. MEASUREMENTS The primary outcome was the serum concentration of α-glutathione S-transferase (α-GST), which reflects hepatic ischemic injury. Secondary outcomes included laboratory variables reflecting inflammatory responses, liver and kidney function, and blood coagulation, as well as hemodynamic changes, recovery variables, and complications related to anesthesia and surgery. RESULTS The concentration of α-GST at 0.5 h after resection was significantly lower in the dexmedetomidine group than the control group (9.1 ± 3.4 ng/mL vs 15.8 ± 6.5 ng/mL; p < .01), and was also significantly lower in the dexmedetomidine group in subgroup analyses of patients with and without hepatic inflow occlusion. While the concentrations of α-GST at 0.5 h after resection in patients with or without occlusion in D group were comparable, in C group the α-GST concentration without occlusion was significantly higher than that with occlusion. There was an interaction between dexmedetomidine and no occlusion (p < .01), and its concentration in D group without occlusion was the lowest of all subgroups. In addition, there were significant differences in interleukin (IL)-6 and tumor necrosis (TNF)-α concentrations at 24 h after hepatectomy between the two groups, and mean arterial pressure, heart rate, and the bispectral index were also significantly lower in D group than in C group (p < .05). There were significant differences between the two groups in ALT and AST at 2 h and 24 h after the resection of the liver lobe. However, there were no significant differences in renal function, recovery variables, blood coagulation. No severe complications related surgeries and anesthesia were found in both groups. CONCLUSION Dexmedetomidine exerts a protective effect on ischemia-reperfusion injury after hepatectomy.
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Affiliation(s)
- Yu Zhang
- Medical School of Chinese PLA, Beijing, China; Anesthesia and Operation Center, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Miao Liu
- Institute of Geriatrics, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yu Yang
- Anesthesia and Operation Center, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Jiangbei Cao
- Anesthesia and Operation Center, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Weidong Mi
- Medical School of Chinese PLA, Beijing, China; Anesthesia and Operation Center, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
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18
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Nguyen TM, Fleyfel M, Boleslawski E, M'Ba L, Geniez M, Ethgen S, Béhal H, Lebuffe G. Effect of pharmacological preconditioning with sevoflurane during hepatectomy with intermittent portal triad clamping. HPB (Oxford) 2019; 21:1194-1202. [PMID: 30773451 DOI: 10.1016/j.hpb.2019.01.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 12/30/2018] [Accepted: 01/18/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND During hepatectomy, intermittent portal triad clamping (IPC) reduces ischemia-reperfusion injuries. Pharmacological preconditioning with sevoflurane revealed similar properties. The aim of the study was to evaluate the combination of a sevoflurane preconditioning regimen with IPC on ischemia-reperfusion injuries. METHODS Three regimens of anesthesia were applied: group SEV with continuous application of sevoflurane, group PRO with continuous propofol infusion and group PC where continuous propofol was substituted by sevoflurane (adjusted to reach MAC∗1.5) for 15 min before IPC. Endpoints were the values of AST and ALT, factor V, prothrombin time, bilirubinemia over the 5-postoperative days (POD), morbidity and mortality at POD30 and POD90. RESULTS The ALT values at POD5 were lower in the PC group (n = 27) 74 (48 -98) IU/L compared to PRO (n = 26) and SEV (n = 67) respectively 110 (75 -152) and 100 (64 -168) IU/L (p = 0.038). The variation of factor V compared to preoperative values was less important in the PC and SEV groups respectively -14% and -16% vs -30% (PRO) (p = 0.047). CONCLUSION Our study suggests that sevoflurane attenuates ischemia-reperfusion injuries on liver function, compared to propofol, without benefit for a specific regimen of pharmacological preconditioning when IPC is applied.
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Affiliation(s)
| | - Maher Fleyfel
- Anesthésie-Réanimation, Hôpital Huriez CHRU Lille, France
| | - Emmanuel Boleslawski
- Service de Chirurgie Digestive et Transplantations, Hôpital Huriez CHRU Lille, France
| | - Léna M'Ba
- Service de Chirurgie Digestive et Transplantations, Hôpital Huriez CHRU Lille, France
| | - Marie Geniez
- Anesthésie-Réanimation, Hôpital Huriez CHRU Lille, France
| | - Sabine Ethgen
- Anesthésie-Réanimation, Hôpital Huriez CHRU Lille, France
| | - Hélène Béhal
- Santé publique: épidémiologie et qualité des soins, Unité de Biostatistiques, CHRU Lille, France
| | - Gilles Lebuffe
- Anesthésie-Réanimation, Hôpital Huriez CHRU Lille, France
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19
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Sipahi M, Gunaydin M, Kesicioglu T, Usta M, Yavuz BT, Tomruk C. A new approach to prevent ischemia/reperfusion injury in a rat model: remote ischemic conditioning. Arch Gynecol Obstet 2019; 299:1691-1699. [DOI: 10.1007/s00404-019-05149-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 04/03/2019] [Indexed: 01/19/2023]
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20
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Latchana N, Hirpara DH, Hallet J, Karanicolas PJ. Red blood cell transfusion in liver resection. Langenbecks Arch Surg 2019; 404:1-9. [PMID: 30607533 DOI: 10.1007/s00423-018-1746-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 12/17/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Several modalities exist for the management of hepatic neoplasms. Resection, the most effective approach, carries significant risk of hemorrhage. Blood loss may be corrected with red blood cell transfusion (RBCT) in the short term, but may ultimately contribute to negative outcomes. PURPOSE Using available literature, we seek to define the frequency and risk factors of blood loss and transfusion following hepatectomy. The impact of blood loss and RBCT on short- and long-term outcomes is explored with an emphasis on peri-operative methods to reduce hemorrhage and transfusion. RESULTS Following hepatic surgery, 25.2-56.8% of patients receive RBCT. Patients who receive RBCT are at increased risk of surgical morbidity in a dose-dependent manner. The relationship between blood transfusion and surgical mortality is less apparent. RBCT might also impact long-term oncologic outcomes including disease recurrence and overall survival. Risk factors for bleeding and blood transfusion include hemoglobin concentration < 12.5 g/dL, thrombocytopenia, pre-operative biliary drainage, presence of background liver disease (such as cirrhosis), coronary artery disease, male gender, tumor characteristics (type, size, location, presence of vascular involvement), extent of hepatectomy, concomitant extrahepatic organ resection, and operative time. Strategies to mitigate blood loss or transfusion include pre-operative (iron, erythropoietin), intra-operative (vascular occlusion, parenchymal transection techniques, hemostatic agents, antifibrinolytics, low central pressure, hemodilution, autologous blood recycling), and post-operative (normothermia, correction of coagulopathy, optimization of nutrition, restrictive transfusion strategy) methods. CONCLUSION Blood loss during hepatectomy is common and several risk factors can be identified pre-operatively. Blood loss and RBCT during hepatectomy is associated with post-operative morbidity and mortality. Disease-free recurrence, disease-specific survival, and overall survival may be associated with blood loss and RBCT during hepatectomy. Attention to pre-operative, intra-operative, and post-operative strategies to reduce blood loss and RBCT is necessary.
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Affiliation(s)
- Nicholas Latchana
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Division of General Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Dhruvin H Hirpara
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Division of General Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Julie Hallet
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Division of General Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Paul J Karanicolas
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
- Division of General Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
- Department of Surgery, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada.
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Riva G, Villanova M, Cima L, Ghimenton C, Bronzoni C, Colombari R, Crestani M, Sina S, Brunelli M, D'Errico A, Montin U, Novelli L, Eccher A. Oil Red O Is a Useful Tool to Assess Donor Liver Steatosis on Frozen Sections During Transplantation. Transplant Proc 2018; 50:3539-3543. [PMID: 30577233 DOI: 10.1016/j.transproceed.2018.06.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 06/19/2018] [Indexed: 02/07/2023]
Abstract
UNLABELLED Oil Red O is a useful tool to assess donor liver steatosis on frozen sections during transplantation. Steatosis is a frequent finding in liver evaluation during transplantation, accounting for 9% to 26% of biopsied donor liver. The degree of macrovesicular steatosis is classified as mild, moderate, and severe; the latter is considered an absolute contraindication to liver transplantation because it is associated with poor allograft outcome. Because of the scarcity of organs, there is a debate whether livers with less severe macrovesicular steatosis are still suitable for transplant. Consequently, tools or methods that allow a more accurate intraoperative assessment of steatosis on frozen sections are mandatory. The aim of this study is to improve intraoperative evaluation of steatosis during transplantation using Oil Red O stain on liver biopsies. METHODS Twenty consecutive liver biopsies of donors were collected during transplantation procedures from September 2017 to February 2018 at the Institute of Pathology of the University and Hospital Trust of Verona, Italy. Each liver biopsy was cut at a different thickness (3, 5, and 8 μm) and stained with both Oil Red O and conventional hematoxylin and eosin for intraoperative consultation. The degree (percentage of hepatocytes involved) of fatty changes was recorded. The results obtained during the intraoperative consultation were finally compared with the formalin-fixed and paraffin-embedded permanent section. RESULTS Assessment of steatosis on hematoxylin and eosin frozen sections was reported as mild in 17 cases (85%), moderate in 2 cases (10%) and severe in 1 case (5%). Oil Red O frozen sections reported the following results: mild steatosis in 16 cases (80%), moderate in 2 cases (10%), and severe in 2 cases (10%). The percentage of liver steatosis obtained with Oil Red O was consistent in all cases with that of the permanent sections. The staining procedure for Oil Red O required approximately 18 minutes. CONCLUSIONS Oil Red O special stain is a fast and inexpensive tool to improve the assessment of steatosis on frozen biopsies during liver transplantation.
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Affiliation(s)
- G Riva
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - M Villanova
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - L Cima
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - C Ghimenton
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - C Bronzoni
- Liver Transplant Unit, Department of Surgical Science, University and Hospital Trust of Verona, Verona, Italy
| | - R Colombari
- Anatomic Pathology, Fracastoro Hospital of San Bonifacio, Verona, Italy
| | - M Crestani
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - S Sina
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - M Brunelli
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - A D'Errico
- Department of Specialty, Diagnostic and Experimental Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Italy
| | - U Montin
- Liver Transplant Unit, Department of Surgical Science, University and Hospital Trust of Verona, Verona, Italy
| | - L Novelli
- Department of Pathology, Careggi University Hospital, Florence, Italy
| | - A Eccher
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy.
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SIRT3 a Major Player in Attenuation of Hepatic Ischemia-Reperfusion Injury by Reducing ROS via Its Downstream Mediators: SOD2, CYP-D, and HIF-1 α. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:2976957. [PMID: 30538800 PMCID: PMC6258096 DOI: 10.1155/2018/2976957] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 09/30/2018] [Accepted: 10/08/2018] [Indexed: 12/14/2022]
Abstract
Reactive oxygen species (ROS) production in hepatic ischemia-reperfusion injury (IRI) is a complex process where multiple cellular and molecular pathways are involved. Few of those molecular pathways are under the direct influence of SIRT3 and its downstream mediators. SIRT3 plays a major role in the mechanism of IRI, and its activation has been shown to attenuate the deleterious effect of ROS during IRI via SOD2-, CYP-D-, and HIF-1α-mediated pathways. The objective of this review is to analyze the current knowledge on SIRT3 and its downstream mediators: SOD2, CYP-D, and HIF-1α, and their role in IRI. For the references of this review article, we have searched the bibliographic databases of PubMed, Web of Science databases, MEDLINE, and EMBASE with the headings "SIRT3," "SOD2," "CYP-D," "HIF-1α," and "liver IRI." Priority was given to recent experimental articles that provide information on ROS modulation by these proteins. All the recent advancement demonstrates that activation of SIRT3 can suppress ROS production during IRI through various pathways and few of those are via SOD2, CYP-D, and HIF-1α. This effect can improve the quality of the remnant liver following resection as well as a transplanted liver. More research is warranted to disclose its role in IRI attenuation via this pathway.
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Mangus R, Kinsella S, Farar D, Fridell J, Woolf L, Kubal C. Impact of Volatile Anesthetic Agents on Early Clinical Outcomes in Liver Transplantation. Transplant Proc 2018; 50:1372-1377. [DOI: 10.1016/j.transproceed.2018.03.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 03/01/2018] [Indexed: 12/19/2022]
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Jeong JS, Kim D, Kim KY, Ryu S, Han S, Shin BS, Kim GS, Gwak MS, Ko JS. Ischemic Preconditioning Produces Comparable Protection Against Hepatic Ischemia/Reperfusion Injury Under Isoflurane and Sevoflurane Anesthesia in Rats. Transplant Proc 2018; 49:2188-2193. [PMID: 29149981 DOI: 10.1016/j.transproceed.2017.07.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 07/30/2017] [Indexed: 11/27/2022]
Abstract
BACKGROUND Various volatile anesthetics and ischemic preconditioning (IP) have been demonstrated to exert protective effect against ischemia/reperfusion (I/R) injury in liver. We aimed to determine whether application of IP under isoflurane and sevoflurane anesthesia would confer protection against hepatic I/R injury in rats. METHODS Thirty-eight rats weighing 270 to 300 grams were randomly divided into 2 groups: isoflurane (1.5%) and sevoflurane (2.5%) anesthesia groups. Each group was subdivided into sham (n = 3), non-IP (n = 8; 45 minutes of hepatic ischemia), and IP (n = 8, IP consisting of 10-minute ischemia plus 15-minute reperfusion before prolonged ischemia) groups. The degree of hepatic injury and expressions of B-cell lymphoma 2 (Bcl-2) and caspase 3 were compared at 2 hours after reperfusion. RESULTS Hepatic ischemia induced significant degree of I/R injuries in both isoflurane and sevoflurane non-IP groups. In both anesthetic groups, introduction of IP dramatically attenuated I/R injuries as marked by significantly lower aspartate aminotransferase and aminotransferase levels and better histologic grades compared with corresponding non-IP groups. There were 2.3- and 1.7-fold increases in Bcl-2 mRNA levels in isoflurane and sevoflurane IP groups, respectively, compared with corresponding non-IP groups (both P < .05). Caspase 3 level was significantly high in the isoflurane non-IP group compared with the sham group; however, there were no differences among the sevoflurane groups. CONCLUSIONS The degree of hepatic I/R injury was significantly high in both isoflurane and sevoflurane groups in rats. However, application of IP significantly protected against I/R injury in both volatile anesthetic groups to similar degrees, and upregulation of Bcl-2 might be an important mechanism.
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Affiliation(s)
- J S Jeong
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - D Kim
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - K Y Kim
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - S Ryu
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - S Han
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - B S Shin
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - G S Kim
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - M S Gwak
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - J S Ko
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Remote Ischemic Preconditioning Is Efficient in Reducing Hepatic Ischemia-Reperfusion Injury in a Growing Rat Model and Does Not Promote Histologic Lesions in Distant Organs. Transplant Proc 2018; 50:3840-3844. [PMID: 30385044 DOI: 10.1016/j.transproceed.2018.04.034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 03/30/2018] [Accepted: 04/12/2018] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Ischemic preconditioning (IPC) was developed to diminish ischemia-reperfusion injury (IRI). There are two main ways of performing it: direct ischemic-preconditioning (DIP) and remote ischemic-preconditioning (RIP). The objectives of this study were to investigate local and systemic effects of DIP and RIP in liver IRI. METHODS Thirty-two weaning rats (50-70 g body weight; 21 days old) were divided into 4 groups: control (C); ischemia followed by reperfusion (IR); DIP followed by ischemia and reperfusion; and RIP followed by ischemia and reperfusion. In the IR group, the vascular pedicles of medial and left lateral liver lobes were clamped for 60 minutes and then unclamped. In the DIP group, a 10-minute cycle of ischemia followed by a 10-minute reperfusion of the same lobes was performed before 60 minutes of ischemia. In the RIP group, three 5-minute cycles of clamping and unclamping of the femoral vessels were performed before liver ischemia. The animals were euthanized 24 hours after the surgical procedures. RESULTS The serum levels of liver enzymes were significantly lower in the RIP group compared to the control and IR groups and to the DIP group. The scores of histologic hepatic lesions were significantly lower in RIP animals than those of IR animals (P = .002) and similar to the C group animals. The Bax/BCl-xl relation was lower in the DIP group than that in the RIP group (P = .045) and no differences were observed in histologic analyses of kidney, lung, intestine, and heart. CONCLUSION In young animals, the beneficial effects of RIP are more evident than those of DIP.
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Krezdorn N, Tasigiorgos S, Wo L, Turk M, Lopdrup R, Kiwanuka H, Win TS, Bueno E, Pomahac B. Tissue conservation for transplantation. Innov Surg Sci 2017; 2:171-187. [PMID: 31579751 PMCID: PMC6754021 DOI: 10.1515/iss-2017-0010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Accepted: 06/27/2017] [Indexed: 02/07/2023] Open
Abstract
Pathophysiological changes that occur during ischemia and subsequent reperfusion cause damage to tissues procured for transplantation and also affect long-term allograft function and survival. The proper preservation of organs before transplantation is a must to limit these injuries as much as possible. For decades, static cold storage has been the gold standard for organ preservation, with mechanical perfusion developing as a promising alternative only recently. The current literature points to the need of developing dedicated preservation protocols for every organ, which in combination with other interventions such as ischemic preconditioning and therapeutic additives offer the possibility of improving organ preservation and extending it to multiple times its current duration. This review strives to present an overview of the current body of knowledge with regard to the preservation of organs and tissues destined for transplantation.
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Affiliation(s)
- Nicco Krezdorn
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Burn Center, Hannover Medical School, Hannover, Germany
| | - Sotirios Tasigiorgos
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Luccie Wo
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Marvee Turk
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Rachel Lopdrup
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Harriet Kiwanuka
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Thet-Su Win
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Ericka Bueno
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Bohdan Pomahac
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
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Abstract
BACKGROUND The protective role (decrease ischemia-reperfusion injury) of ischemic preconditioning (IP) before continuous vascular occlusion in liver resection is controversial. This meta-analysis aimed to compare the advantages and any potential disadvantages of IP maneuver. METHODS A systematic search in the Embase, Medline, PubMed databases, and the Cochrane Library was performed using both medical subject headings (MeSH) and truncated word searches to identify all randomized controlled trials (RCTs) published on this topic. The primary outcomes were postoperative morbidity, mortality, postoperative aspartate aminotransferase (AST) level, alanine aminotransferase (ALT) level, and total bilirubin (TB) level. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were calculated using either the random effects model or fixed effects model. RESULTS Thirteen RCTs involving 918 patients were analyzed to achieve a summated outcome. The patients have been divided into IP group (n = 455) and no IP group (n = 463) before continuous vascular occlusion. No significant difference was found in postoperative mortality between both groups (P = .30). Subgroup analysis revealed that the postoperative morbidity in the cirrhosis subgroup was significantly less for the IP group compared with the control group (P = .01). In the cirrhosis subgroup, the result was stable (P = .04), without heterogeneity (P = .59; I = 0%). Meta-analysis of AST level on postoperative day (POD) 1 indicated lower postoperative AST level in the IP group (P = .04). The analysis of ALT level showed lower ALT level in the IP group versus control group (P = .02). However, there was no difference in postoperative AST and ALT level after excluding 1 study with statistical heterogeneity (all P > .05). With respect to postoperative TB level, there was no significant difference between 2 groups. CONCLUSION IP cannot decrease the hospital mortality for patients undergoing hepatectomy. IP may be beneficial for patients with cirrhosis due to less morbidity in patients with liver cirrhosis. However, we cannot conclude that IP can decrease ischemia-reperfusion injury because it did not significantly decrease postoperative AST, ALT, and TB levels.
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Alleviation of Ischemia-Reperfusion Injury in Liver Steatosis by Augmenter of Liver Regeneration Is Attributed to Antioxidation and Preservation of Mitochondria. Transplantation 2017; 101:2340-2348. [PMID: 28704337 DOI: 10.1097/tp.0000000000001874] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Fatty liver is one of the major impediments to liver surgery and liver transplantation because steatotic hepatocytes are more susceptible to ischemia-reperfusion injury (IRI). In this study, the effects of augmenter of liver regeneration (ALR) on hepatic IRI in steatotic mice were investigated. METHODS In vivo, liver steatosis of mice was induced by feeding a methionine-choline-deficient diet for 2 weeks. Three days before hepatic partial warm IRI, mice were transfected with the ALR-containing adenovirus. In an in vitro study, the protective effect of ALR on steatotic HepG2 cells was analyzed after hypoxia/reoxygenation (HR) treatment. RESULTS The transfection of the ALR gene into steatotic mice attenuated liver injury, inhibiting hepatic oxidative stress, increasing antioxidation capacities, promoting liver regeneration, and consequently suppressing cell apoptosis/death. Furthermore, resistance to HR injury was notably increased in ALR-transfected cells compared with the vector-transfected cells. The HR-induced rise in the mitochondrial reactive oxygen species was reduced, and cellular antioxidant activities were enhanced. The ALR transfection prevented cells from apoptosis, which can be attributed to the preservation of the mitochondrial membrane potential, enhancement of oxygen consumption rate and production of adenosine triphosphate. CONCLUSIONS ALR protects steatotic hepatocytes from IRI by attenuating oxidative stress and mitochondrial dysfunction, as well as improving antioxidant effect. ALR may be used as a potential therapeutic agent when performing surgery and transplantation of steatotic liver.
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Yoshino O, Perini MV, Christophi C, Weinberg L. Perioperative fluid management in major hepatic resection: an integrative review. Hepatobiliary Pancreat Dis Int 2017; 16:458-469. [PMID: 28992877 DOI: 10.1016/s1499-3872(17)60055-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2016] [Accepted: 04/10/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND Fluid intervention and vasoactive pharmacological support during hepatic resection depend on the preference of the attending clinician, institutional resources, and practice culture. Evidence-based recommendations to guide perioperative fluid management are currently limited. Therefore, we provide a contemporary clinical integrative overview of the fundamental principles underpinning fluid intervention and hemodynamic optimization for adult patients undergoing major hepatic resection. DATA SOURCES A literature review was performed of MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials using the terms "surgery", "anesthesia", "starch", "hydroxyethyl starch derivatives", "albumin", "gelatin", "liver resection", "hepatic resection", "fluids", "fluid therapy", "crystalloid", "colloid", "saline", "plasma-Lyte", "plasmalyte", "hartmann's", "acetate", and "lactate". Search results for MEDLINE and EMBASE were additionally limited to studies on human populations that included adult age groups and publications in English. RESULTS A total of 113 articles were included after appropriate inclusion criteria screening. Perioperative fluid management as it relates to various anesthetic and surgical techniques is discussed. CONCLUSIONS Clinicians should have a fundamental understanding of the surgical phases of the resection, hemodynamic goals, and anesthesia challenges in attempts to individualize therapy to the patient's underlying pathophysiological condition. Therefore, an ideal approach for perioperative fluid therapy is always individualized. Planning and designing large-scale clinical trials are imperative to define the optimal type and amount of fluid for patients undergoing major hepatic resection. Further clinical trials evaluating different intraoperative goal-directed strategies are also eagerly awaited.
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Affiliation(s)
- Osamu Yoshino
- Department of Surgery, Austin Hospital and University of Melbourne, Melbourne, Victoria, Australia.
| | - Marcos Vinicius Perini
- Department of Surgery, Austin Hospital and University of Melbourne, Melbourne, Victoria, Australia
| | - Christopher Christophi
- Department of Surgery, Austin Hospital and University of Melbourne, Melbourne, Victoria, Australia
| | - Laurence Weinberg
- Department of Surgery, Austin Hospital and University of Melbourne, Melbourne, Victoria, Australia; Anaesthesia Perioperative Pain Medicine Unit, University of Melbourne, Melbourne, Victoria, Australia
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Remote Ischemic Preconditioning: A Novel Strategy in Rescuing Older Livers From Ischemia-reperfusion Injury in a Rodent Model. Ann Surg 2017; 264:797-803. [PMID: 27584570 DOI: 10.1097/sla.0000000000001765] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The aim of this study was to determine whether remote ischemic preconditioning (RIPC) protects aged liver against ischemia reperfusion (IR). SUMMARY OF BACKGROUND DATA The demands for liver surgery in an aging population are growing. Clamping of vessels to prevent blood loss is integral to liver surgery, but the resulting IR injury (IRI) augments postoperative complications. More so, sensitivity to hepatic IRI increases with age; however, no strategies have been developed that specifically protect old liver. RIPC, a novel protective approach, was performed distant to the surgical site. Whether RIPC may also protect old liver from IRI is unknown. METHODS RIPC to the femoral vascular bundle was compared against direct ischemic preconditioning (IPC) and the standard of care intermittent clamping (IC) using a model of partial hepatic ischemia in mice aged 20 to 24 months. Liver injury was measured 6 hours after reperfusion. Protective signaling (serotonin-Vegf-Il10/Mmp8 axis, Kupffer cell polarization) was assessed immediately after preconditioning. Neutralizing antibody was used to test the role of Vegf. Hepatic vasculature was examined by electron microscopy. RESULTS RIPC was superior over other strategies in protecting old liver from IRI, with standard IPC approaches being ineffective. RIPC induced the strongest elevations in circulating Vegf, and Vegf inhibition dampened protective signaling and abrogated the protective effects. RIPC was further associated with improvements in vascular functionality. CONCLUSIONS RIPC is highly effective in protecting old liver from ischemic insults, mainly owing to its ability to induce circulating Vegf. These findings warrant efforts toward clinical translation.
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Dupré A, Pérol D, Blanc E, Peyrat P, Basso V, Chen Y, Vincenot J, Kocot A, Melodelima D, Rivoire M. Efficacy of high-intensity focused ultrasound-assisted hepatic resection (HIFU-AR) on blood loss reduction in patients with liver metastases requiring hepatectomy: study protocol for a randomized controlled trial. Trials 2017; 18:57. [PMID: 28166812 PMCID: PMC5294714 DOI: 10.1186/s13063-017-1801-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 01/16/2017] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Liver resection is the only potentially curative treatment for colorectal liver metastases (LM). It is considered a safe procedure, but is often associated with blood loss during liver transection. Blood transfusions are frequently needed, but they are associated with increased morbidity and risk of recurrence. Many surgical devices have been developed to decrease blood loss. However, none of them has proven superior to the standard crushing technique. We developed a new, powerful intra-operative high-intensity focused ultrasound (HIFU) transducer which destroys tissue by coagulative necrosis. We aim to evaluate whether HIFU-assisted liver resection (HIFU-AR) results in reduced blood loss. METHODS This is a prospective, single-centre, randomized (1:1 ratio), comparative, open-label phase II study. Patients with LM requiring a hepatectomy for ≥ 2 segments will be included. Patients with cirrhosis or sinusoidal obstruction syndrome with portal hypertension will be excluded. The primary endpoint is normalized blood loss in millilitres per square centimetre of liver section plane. Secondary endpoints are: total blood loss, transection time, transection time per square centimetre of liver area, haemostasis time, clip density on the liver section area, rate and duration of the Pringle manœuvre, rate of patients needing a blood transfusion, length of hospital stay, morbidity, patients with positive resection margin, and local recurrence. Assuming a blood loss of 7.6 ± 3.7 mL/cm2 among controls, the study will have 85% power to detect a twofold decrease of blood loss in the experimental arm, using a Wilcoxon (Mann-Whitney) rank-sum test with a 0.05 two-sided significance level. Twenty-one randomized patients per arm are required. Considering the risk of contraindications at surgery, up to eight patients may be enrolled in addition to the 42 planned, with an enrolment period of 24 months. Randomization will be stratified by surgeon. DISCUSSION We previously demonstrated the safety and efficacy of intra-operative HIFU in patients operated on for LM. We also demonstrated the efficacy of HIFU-AR in a preclinical study. Participants in the HIFU-AR group of this randomized trial can expect to benefit from reduced blood loss and decreased ischemia of liver parenchyma. TRIAL REGISTRATION Clinicaltrial.gov, NCT02728167 . Registered on 22 March 2016.
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Affiliation(s)
- Aurélien Dupré
- Department of Surgical Oncology, Centre Léon Bérard, 28 Rue Laennec, Lyon, 69008, France. .,Inserm, U1032, LabTau, University of Lyon, Lyon, 69003, France.
| | - David Pérol
- Department of Clinical Research (DRCI), Centre Léon Bérard, Lyon, 69008, France
| | - Ellen Blanc
- Department of Clinical Research (DRCI), Centre Léon Bérard, Lyon, 69008, France
| | - Patrice Peyrat
- Department of Surgical Oncology, Centre Léon Bérard, 28 Rue Laennec, Lyon, 69008, France
| | - Valéria Basso
- Department of Surgical Oncology, Centre Léon Bérard, 28 Rue Laennec, Lyon, 69008, France
| | - Yao Chen
- Department of Surgical Oncology, Centre Léon Bérard, 28 Rue Laennec, Lyon, 69008, France
| | - Jérémy Vincenot
- Inserm, U1032, LabTau, University of Lyon, Lyon, 69003, France
| | - Anthony Kocot
- Inserm, U1032, LabTau, University of Lyon, Lyon, 69003, France
| | | | - Michel Rivoire
- Department of Surgical Oncology, Centre Léon Bérard, 28 Rue Laennec, Lyon, 69008, France.,Inserm, U1032, LabTau, University of Lyon, Lyon, 69003, France
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Zhang W, Wang J, Li C, Zhang Z, Dirie NI, Dong H, Xiang S, Zhang W, Zhang Z, Zhang B, Chen X. Infrahepatic inferior vena cava clamping with Pringle maneuvers for laparoscopic extracapsular enucleation of giant liver hemangiomas. Surg Endosc 2017; 31:3628-3636. [PMID: 28130585 PMCID: PMC5579183 DOI: 10.1007/s00464-016-5396-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Accepted: 12/15/2016] [Indexed: 12/12/2022]
Abstract
Background This study aimed to determine the feasibility of the extracapsular enucleation method for giant liver hemangiomas by infrahepatic inferior vena cava (IVC) clamping and the Pringle maneuver to control intraoperative bleeding under laparoscopic hepatectomy. Methods From January 2012 to January 2016, 36 patients underwent laparoscopic extracapsular enucleation of giant liver hemangiomas. Patients were divided into two groups: infrahepatic IVC clamping + Pringle maneuvers group (IVCP group, n = 15) and the Pringle maneuvers group (Pringle group, n = 21). Operative parameters, postoperative laboratory tests, and morbidity and mortality were analyzed. Results The mean size of liver hemangiomas was 13.3 cm (range 10–25 cm). Infrahepatic IVC clamping + the Pringle maneuvers with laparoscopic extracapsular enucleation significantly reduced intraoperative blood loss (586.7 vs 315.3 mL, p < 0.001) and transfusion rates (23.8 vs 6.7%, p = 0.001), compared with the Pringle maneuver alone. The gallbladder was retained in both groups. The mean arterial pressure (MAP) in Pringle group remained virtually stable before and after clamping of hepatic portal, while it was significantly decreased after IVC clamping in IVCP group than that pre-clamping (p < 0.001). The heart rate of all patients was significantly increased after clamping when compared to pre-clamping heart rates (p < 0.001). Once vascular occlusion was released, MAP returned to normal levels within a few minutes. There were no significant differences in postoperative complications between two groups. The vascular occlusion techniques in both groups had no serious effect on postoperative of hepatic and renal function. Conclusions Extracapsular enucleation with infrahepatic IVC clamping + the Pringle maneuver is a safe and effective surgical treatment to control bleeding for giant liver hemangiomas in laparoscopic hepatectomy.
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Affiliation(s)
- Wanguang Zhang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian Wang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Changhai Li
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhanguo Zhang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Najib Isse Dirie
- Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hanhua Dong
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuai Xiang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Zhang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiwei Zhang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bixiang Zhang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoping Chen
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Hao S, Chen S, Yang X, Wan C. Adverse impact of intermittent portal clamping on long-term postoperative outcomes in hepatocellular carcinoma. Ann R Coll Surg Engl 2017; 99:22-27. [PMID: 27269234 PMCID: PMC5392778 DOI: 10.1308/rcsann.2016.0183] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/11/2016] [Indexed: 01/28/2023] Open
Abstract
Introduction To evaluate the impact of intermittent portal clamping (IPC) on long-term postoperative outcomes in patients with hepatocellular carcinoma (HCC). Methods Clinical records of 355 patients underwent curative liver resection for HCC in January 2007 to December 2010 were retrospectively reviewed. According to how portal clamping was performed, patients were grouped as: IPC, n=113; other portal clamping (OPC), n=190; and no portal clamping (NPC), n=52. Results Median recurrence-free survival (RFS) was statistically significantly shorter in the IPC (39.4 months) than OPC (47.3 months, p=0.010) and NPC groups (51.4 months, p=0.008). Median overall survival (OS) was also significantly shorter with IPC (46.3 months), versus 52.9 months with OPC (p=0.022) and 56.2 months with NPC (p=0.015). Kaplan-Meier survival analysis revealed that 5-year cumulative RFS was much lower in the IPC (42.5%) than OPC (50.9%, p=0.014) and NPC groups (49.6%, p=0.013). Five-year cumulative OS was also much lower in the IPC (44.9%) than OPC (58.0%, p=0.020) and NPC groups (57.7%, p=0.025). On univariate analysis, tumour grade, size and number, TNM stage, blood transfusion, vascular invasion and IPC were significantly inversely correlated with RFS and OS. On multivariate analysis, tumour size and number, blood transfusion, vascular invasion and IPC remained significant. Conclusions Our study suggests that IPC is an independent risk factor for poor long-term postoperative outcomes in patients with HCC.
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Affiliation(s)
- S Hao
- Huazhong University of Science and Technology , Wuhan , China
| | - S Chen
- Huazhong University of Science and Technology , Wuhan , China
| | - X Yang
- Central South University , Changsha , China
| | - C Wan
- Huazhong University of Science and Technology , Wuhan , China
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Go KL, Lee S, Behrns KE, Kim JS. Mitochondrial Damage and Mitophagy in Ischemia/Reperfusion-Induced Liver Injury. MOLECULES, SYSTEMS AND SIGNALING IN LIVER INJURY 2017:183-219. [DOI: 10.1007/978-3-319-58106-4_9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Moggia E, Rouse B, Simillis C, Li T, Vaughan J, Davidson BR, Gurusamy KS, Cochrane Hepato‐Biliary Group. Methods to decrease blood loss during liver resection: a network meta-analysis. Cochrane Database Syst Rev 2016; 10:CD010683. [PMID: 27797116 PMCID: PMC6472530 DOI: 10.1002/14651858.cd010683.pub3] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Liver resection is a major surgery with significant mortality and morbidity. Specialists have tested various methods in attempts to limit blood loss, transfusion requirements, and morbidity during elective liver resection. These methods include different approaches (anterior versus conventional approach), use of autologous blood donation, cardiopulmonary interventions such as hypoventilation, low central venous pressure, different methods of parenchymal transection, different methods of management of the raw surface of the liver, different methods of vascular occlusion, and different pharmacological interventions. A surgeon typically uses only one of the methods from each of these seven categories. The optimal method to decrease blood loss and transfusion requirements in people undergoing liver resection is unknown. OBJECTIVES To assess the effects of different interventions for decreasing blood loss and blood transfusion requirements during elective liver resection. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Science Citation Index Expanded to September 2015 to identify randomised clinical trials. We also searched trial registers and handsearched the references lists of identified trials. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different methods of decreasing blood loss and blood transfusion requirements in people undergoing liver resection. DATA COLLECTION AND ANALYSIS Two review authors independently identified trials and collected data. We assessed the risk of bias using Cochrane domains. We conducted a Bayesian network meta-analysis using the Markov chain Monte Carlo method in WinBUGS 1.4, following the guidelines of the National Institute for Health and Care Excellence Decision Support Unit guidance documents. We calculated the odds ratios (OR) with 95% credible intervals (CrI) for the binary outcomes, mean differences (MD) with 95% CrI for continuous outcomes, and rate ratios with 95% CrI for count outcomes, using a fixed-effect model or random-effects model according to model-fit. We assessed the evidence with GRADE. MAIN RESULTS We identified 67 randomised clinical trials involving a total of 6197 participants. All the trials were at high risk of bias. A total of 5771 participants from 64 trials provided data for one or more outcomes included in this review. There was no evidence of differences in most of the comparisons, and where there was, these differences were in single trials, mostly of small sample size. We summarise only the evidence that was available in more than one trial below. Of the primary outcomes, the only one with evidence of a difference from more than one trial under the pair-wise comparison was in the number of adverse events (complications), which was higher with radiofrequency dissecting sealer than with the clamp-crush method (rate ratio 1.85, 95% CrI 1.07 to 3.26; 250 participants; 3 studies; very low-quality evidence). Among the secondary outcomes, the only differences we found from more than one trial under the pair-wise comparison were the following: blood transfusion (proportion) was higher in the low central venous pressure group than in the acute normovolemic haemodilution plus low central venous pressure group (OR 3.19, 95% CrI 1.56 to 6.95; 208 participants; 2 studies; low-quality evidence); blood transfusion quantity (red blood cells) was lower in the fibrin sealant group than in the control (MD -0.53 units, 95% CrI -1.00 to -0.07; 122 participants; 2; very low-quality evidence); blood transfusion quantity (fresh frozen plasma) was higher in the oxidised cellulose group than in the fibrin sealant group (MD 0.53 units, 95% CrI 0.36 to 0.71; 80 participants; 2 studies; very low-quality evidence); blood loss (MD -0.34 L, 95% CrI -0.46 to -0.22; 237 participants; 4 studies; very low-quality evidence), total hospital stay (MD -2.42 days, 95% CrI -3.91 to -0.94; 197 participants; 3 studies; very low-quality evidence), and operating time (MD -15.32 minutes, 95% CrI -29.03 to -1.69; 192 participants; 4 studies; very low-quality evidence) were lower with low central venous pressure than with control. For the other comparisons, the evidence for difference was either based on single small trials or there was no evidence of differences. None of the trials reported health-related quality of life or time needed to return to work. AUTHORS' CONCLUSIONS Paucity of data meant that we could not assess transitivity assumptions and inconsistency for most analyses. When direct and indirect comparisons were available, network meta-analysis provided additional effect estimates for comparisons where there were no direct comparisons. However, the paucity of data decreases the confidence in the results of the network meta-analysis. Low-quality evidence suggests that liver resection using a radiofrequency dissecting sealer may be associated with more adverse events than with the clamp-crush method. Low-quality evidence also suggests that the proportion of people requiring a blood transfusion is higher with low central venous pressure than with acute normovolemic haemodilution plus low central venous pressure; very low-quality evidence suggests that blood transfusion quantity (red blood cells) was lower with fibrin sealant than control; blood transfusion quantity (fresh frozen plasma) was higher with oxidised cellulose than with fibrin sealant; and blood loss, total hospital stay, and operating time were lower with low central venous pressure than with control. There is no evidence to suggest that using special equipment for liver resection is of any benefit in decreasing the mortality, morbidity, or blood transfusion requirements (very low-quality evidence). Radiofrequency dissecting sealer should not be used outside the clinical trial setting since there is low-quality evidence for increased harm without any evidence of benefits. In addition, it should be noted that the sample size was small and the credible intervals were wide, and we cannot rule out considerable benefit or harm with a specific method of liver resection.
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Affiliation(s)
- Elisabetta Moggia
- IRCCS Humanitas Research HospitalDepartment of General and Digestive SurgeryVia Manzoni 5620089 RozzanoMilanItalyItaly20089
| | - Benjamin Rouse
- Johns Hopkins Bloomberg School of Public HealthDepartment of Epidemiology615 N. Wolfe StreetBaltimoreMarylandUSA21205
| | - Constantinos Simillis
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRoyal Free HospitalRowland Hill StreetLondonUKNW3 2PF
| | - Tianjing Li
- Johns Hopkins Bloomberg School of Public HealthDepartment of Epidemiology615 N. Wolfe StreetBaltimoreMarylandUSA21205
| | - Jessica Vaughan
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRoyal Free HospitalRowland Hill StreetLondonUKNW3 2PF
| | - Brian R Davidson
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRoyal Free HospitalRowland Hill StreetLondonUKNW3 2PF
| | - Kurinchi Selvan Gurusamy
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRoyal Free HospitalRowland Hill StreetLondonUKNW3 2PF
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Modern Technical Approaches in Hepatic Surgery for Colorectal Metastases. CURRENT COLORECTAL CANCER REPORTS 2016. [DOI: 10.1007/s11888-016-0327-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Adherence to early mobilisation: Key for successful enhanced recovery after liver resection. Eur J Surg Oncol 2016; 42:1561-7. [PMID: 27528466 DOI: 10.1016/j.ejso.2016.07.015] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 07/18/2016] [Accepted: 07/25/2016] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Enhanced Recovery After Surgery (ERAS) has been proven effective in liver surgery. Adherence to the ERAS pathway is variable. This study seeks to evaluate adherence to key components of an ERAS protocol in liver resection, and identify the components associated with successful clinical outcomes. METHOD All patients undergoing liver resections for two consecutive years were included in our ERAS pathway. Six key components of ERAS included preoperative assessment, nutrition and gastrointestinal function, postoperative analgesia, mobilisation and discharges. Successful accomplishment of ERAS was defined as hospital discharge by postop day (POD) 6. Adherences of these elements were compared between the successful and un-successful groups. RESULTS During the studied period, 223 patients underwent liver resections, among which 103 had major hepatectomies. N = 147 patients (66%) were discharged within our ERAS protocol target (6 days). On multivariable analysis, sitting out of bed by POD 1 (p < 0.03), walking by POD 3 (p = 0.03), removal of urinary catheter by POD 3 (p < 0.01), and avoiding major complications (p < 0.01) were factors associated with successful completion to our ERAS protocol; whereas advanced age (p = 0.34) and discontinuation of PCA/epidural by POD 3 (p = 0.50) were not significant parameters. There was a significant difference in the length of stay (p < 0.01) following major and minor liver resection, of which the indications for surgery also varied significantly. There was no difference in hospital re-admission rate, and morbidity and mortality between major and minor liver resection. CONCLUSIONS Facilitating early mobilisation and reducing postoperative complications are keys to successful outcomes of ERAS in liver resection.
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Hau HM, Tautenhahn HM, Schmelzle M, Morgul HM, Moche M, Bartels M, Uhlmann D. Current strategies for preoperative conditioning of the liver to expand criteria for resectability of hepatic metastases. Eur Surg 2016; 48:180-190. [DOI: 10.1007/s10353-015-0381-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Blood transfusion is an independent predictor of morbidity and mortality after hepatectomy. J Surg Res 2016; 206:106-112. [PMID: 27916348 DOI: 10.1016/j.jss.2016.07.013] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 04/26/2016] [Accepted: 07/07/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND Previous studies have indicated that blood transfusion is associated with increased risk of worse outcomes among patients selected for hepatectomy. However, the independent effect of transfusion has not been confirmed. We hypothesize that blood transfusion is an independent factor that affects outcomes in patients undergoing hepatectomy. MATERIALS AND METHODS Patients at tertiary care center who underwent hepatectomy between 2006 and 2013 were identified and linked with the American College of Surgeons National Surgical Quality Improvement Program PUF data set. Multivariable logistic regression analysis was used to estimate the effect of blood transfusion on 30-d mortality and morbidity, adjusted for differences in extent of resection and estimated probabilities of morbidity and mortality. RESULTS Among 522 patients in the study, 48 (9.2%) patients required perioperative blood transfusion within 72 h of resection, and 172 (33%) underwent major hepatectomy. Indications for hepatectomy included metastatic neoplasm (n = 229, 44%), primary hepatic neoplasm (n = 108, 21%), primary extra-hepatic biliary neoplasm (n = 23, 4%), and nonmalignant indications (n = 162, 31%). Eighty-eight (17%) patients had a postoperative morbidity. Blood transfusion was significantly associated with postoperative morbidity (odds ratio [OR] = 4.18, 95% CI = 2.18-8.02, P = 0.0001) and mortality (OR = 14.5, 95% CI = 3.08-67.8, P = 001), after adjustment for the concurrent effect of National Surgical Quality Improvement Program estimated probability of morbidity (OR = 1.15, 95% CI = 0.11-12.2, P = 0.042). The extent of resection was not significantly associated with morbidity (OR = 1.30, 95% CI, 0.74-2.28, P = 0.366) or mortality (OR = 1.14, 95% CI = 0.24-5.50, P = 0.870). CONCLUSIONS Blood transfusion is a highly statistically significant independent predictor of morbidity and mortality after hepatectomy. Judicious use of perioperative transfusion is indicated in patients with benign and malignant indications for liver resection.
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Simillis C, Robertson FP, Afxentiou T, Davidson BR, Gurusamy KS. A network meta-analysis comparing perioperative outcomes of interventions aiming to decrease ischemia reperfusion injury during elective liver resection. Surgery 2016; 159:1157-69. [DOI: 10.1016/j.surg.2015.10.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2015] [Revised: 09/05/2015] [Accepted: 10/01/2015] [Indexed: 12/12/2022]
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Mitochondrial Dysfunction and Autophagy in Hepatic Ischemia/Reperfusion Injury. BIOMED RESEARCH INTERNATIONAL 2015; 2015:183469. [PMID: 26770970 PMCID: PMC4684839 DOI: 10.1155/2015/183469] [Citation(s) in RCA: 94] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 11/10/2015] [Accepted: 11/11/2015] [Indexed: 12/26/2022]
Abstract
Ischemia/reperfusion (I/R) injury remains a major complication of liver resection, transplantation, and hemorrhagic shock. Although the mechanisms that contribute to hepatic I/R are complex and diverse involving the interaction of cell injury in hepatocytes, immune cells, and endothelium, mitochondrial dysfunction is a cardinal event culminating in hepatic reperfusion injury. Mitochondrial autophagy, so-called mitophagy, is a key cellular process that regulates mitochondrial homeostasis and eliminates damaged mitochondria in a timely manner. Growing evidence accumulates that I/R injury is attributed to defective mitophagy. This review aims to summarize the current understanding of autophagy and its role in hepatic I/R injury and highlight the various therapeutic approaches that have been studied to ameliorate injury.
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Simillis C, Li T, Vaughan J, Becker LA, Davidson BR, Gurusamy KS. A Cochrane systematic review and network meta-analysis comparing treatment strategies aiming to decrease blood loss during liver resection. Int J Surg 2015; 23:128-36. [PMID: 26432546 DOI: 10.1016/j.ijsu.2015.09.064] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Revised: 09/07/2015] [Accepted: 09/24/2015] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Intraoperative haemorrhage remains one of the major risks during liver resection, and perioperative blood loss and blood transfusion are important factors affecting perioperative morbidity and mortality. The aim of this study is to compare treatment strategies aiming to decrease blood loss during hepatectomy. METHODS A systematic review of the literature was performed to identify randomised controlled trials reporting on the method of vascular occlusion, parenchymal transection, and management of the cut surface during liver resection. A Bayesian network meta-analysis was performed using WinBUGS. RESULTS Seven trials reporting on 496 participants randomised to seven treatment strategies were analysed. Continuous vascular occlusion resulted in lower blood loss compared to no vascular occlusion when parenchymal transection was performed with clamp-crush and no fibrin sealant was used for the cut surface. People undergoing liver resection by continuous vascular occlusion had decreased amounts of blood transfused than people with intermittent vascular occlusion when parenchymal transection was performed with clamp-crush and no fibrin sealant. There was no significant difference in proportion of people transfused, mortality, or hospital stay between the different strategies. There were significantly more serious adverse events when surgery was performed using radiofrequency dissecting sealer compared with standard clamp-crush method in the absence of vascular occlusion and fibrin sealant. CONCLUSIONS Continuous vascular occlusion during hepatectomy results in decreased blood loss and decreased blood transfusion requirements. Further studies are needed to compare treatment strategies aiming to decrease blood loss, defined by their method of vascular occlusion, parenchymal transection, and management of the cut surface.
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Affiliation(s)
| | - Tianjing Li
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Jessica Vaughan
- Department of Surgery, Royal Free Campus, UCL Medical School, London, UK
| | - Lorne A Becker
- Department of Family Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Brian R Davidson
- Department of Surgery, Royal Free Campus, UCL Medical School, London, UK
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Dimitroulis D, Moris D, Pikoulis E, Spartalis E, Kontadakis G, Vrugt B, Valsami S, Kouraklis G. Variable Pringle Maneuvers and Effect on Intestinal Epithelium in Rats. A Pilot Experimental Study in Rats. PLoS One 2015; 10:e0140707. [PMID: 26496481 PMCID: PMC4619866 DOI: 10.1371/journal.pone.0140707] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 09/28/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND It is observed that combined liver and colon surgery especially when this includes major liver resection with Pringle maneuver (PM) performance does not have a favorable outcome. Aim of our experimental study is to investigate the impact of portal triad occlusion on the large bowel and intra-abdominal inflammation and potent protective effects of the variants of (PM) in the combined surgical cases. MATERIALS AND METHODS Forty-four rats were divided into four groups. In group A (control group), 1cm of the left partial colon was resected and then an end-to-end anastomosis was performed. In group B, a continuous PM for 30 minutes was performed followed by resection of 1cm of the left colon and an end-to-end anastomosis. In group C, the left colonic resection and anastomosis was performed after intermittent PM (IPM), which was 10 minutes PM followed by 5 minutes reperfusion repeated for three circles. In group D, an ischemic preconditioning for 10 minutes was initially performed followed by 5 minutes reperfusion and then continuous PM for 30 minutes. Finally the rats in group D underwent a 1cm left colonic resection and an end-to-end anastomosis. RESULTS The percentage of colitis was higher in the B group (P = 0,19). The percentage of inflammation was not significantly higher even when we compared all "occlusion" groups (B+C+D) with the sham group. No evidence of pancreatitis was found in the sham group whereas amylase and lipase levels were higher in Groups B, C and D together (P = 0,0267). The comparison of group A to group B showed a significant difference (P = 0,0014) caused by continuous PM for 30 minutes, but there was no such result after IPM. CONCLUSIONS Major liver resections are performed with PM in order to minimize intra-operative blood loss. In the combined cases of colon surgery and major liver resections where PM is needed our results showed that IPM presents with better outcome and could be preferred compared with the other PM variants.
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Affiliation(s)
- Dimitrios Dimitroulis
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Demetrios Moris
- First Department of Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Emmanouil Pikoulis
- First Department of Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Eleftherios Spartalis
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Kontadakis
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Bart Vrugt
- Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, Zürich, Switzerland
| | - Serena Valsami
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Gregory Kouraklis
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Tashiro H, Kuroda S, Mikuriya Y, Ohdan H. Ischemia–reperfusion injury in patients with fatty liver and the clinical impact of steatotic liver on hepatic surgery. Surg Today 2015; 44:1611-25. [PMID: 24078000 DOI: 10.1007/s00595-013-0736-9] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Accepted: 08/22/2013] [Indexed: 12/15/2022]
Abstract
Hepatic steatosis is one of the most common hepatic disorders in developed countries. The epidemic of obesity in developed countries has increased with its attendant complications, including metabolic syndrome and non-alcoholic fatty liver disease. Steatotic livers are particularly vulnerable to ischemia/reperfusion injury, resulting in an increased risk of postoperative morbidity and mortality after liver surgery, including liver transplantation. There is growing understanding of the molecular and cellular mechanisms and therapeutic approaches for treating ischemia/reperfusion injury in patients with steatotic livers. This review discusses the mechanisms underlying the susceptibility of steatotic livers to ischemia/reperfusion injuries, such as mitochondrial dysfunction and signal transduction alterations, and summarizes the clinical impact of steatotic livers in the setting of hepatic resection and liver transplantation. This review also describes potential therapeutic approaches, such as ischemic and pharmacological preconditioning, to prevent ischemia/reperfusion injury in patients with steatotic livers. Other approaches, including machine perfusion, are also under clinical investigation; however, many pharmacological approaches developed through basic research are not yet suitable for clinical application.
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Riediger C, Mueller MW, Hapfelmeier A, Bachmann J, Friess H, Kleeff J. Preoperative Serum Bilirubin and Lactate Levels Predict Postoperative Morbidity and Mortality in Liver Surgery: A Single-Center Evaluation. Scand J Surg 2015; 104:176-184. [DOI: 10.1177/1457496914548093] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
Background and Aims: In spite of huge developments in liver surgery during the last decades, morbidity and mortality continue to pose problems in this field. The aim of this study was to identify preoperative predictors for postoperative mortality and morbidity in liver surgery. Material and Methods: In a single-center study, an extensive analysis of a prospective database, including clinical criteria and laboratory tests of patients undergoing liver surgery between July 2007 and July 2012 was performed. Cutoff values of selected laboratory tests were calculated. Results: In all, 337 patients were included in the study. Univariate analysis showed a statistically significant association of preoperative bilirubin, lactate, hemoglobin levels, platelet count, and prothrombin time with postoperative morbidity and mortality. Multivariate analysis revealed preoperatively elevated serum bilirubin and lactate levels as independent predictors for increased postoperative morbidity and mortality after liver surgery. Conclusions: The identified laboratory values showed a statistically significant association with postoperative morbidity and mortality in liver surgery and might be helpful in preoperative patient selection.
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Affiliation(s)
- C. Riediger
- Department of Surgery, Technische Universität München, Munich, Germany
- Department of General, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - M. W. Mueller
- Department of Surgery, Technische Universität München, Munich, Germany
- Department of Surgery, Krankenhaus Bad Cannstatt, Klinikum Stuttgart, Stuttgart, Germany
| | - A. Hapfelmeier
- Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany
| | - J. Bachmann
- Department of Surgery, Technische Universität München, Munich, Germany
| | - H. Friess
- Department of Surgery, Technische Universität München, Munich, Germany
| | - J. Kleeff
- Department of Surgery, Technische Universität München, Munich, Germany
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Abstract
Cold-inducible RNA-binding protein (CIRP) is a nuclear protein that has been recently identified as a novel inflammatory mediator in hemorrhagic shock and sepsis. We hypothesized that CIRP acts as a potent inflammatory mediator in hepatic ischemia-reperfusion (I/R), and thus blocking CIRP protects against I/R-induced liver injury. Male C57BL/6 mice were subjected to 70% hepatic ischemia by microvascular clamping of the hilum of the left and median liver lobes for 60 min, followed by reperfusion. Anti-CIRP antibody (1 mg/kg body weight) or vehicle (normal saline) in 0.2 mL was injected via the internal jugular vein at the beginning of the reperfusion. Blood and liver tissues were collected 24 h after I/R for various measurements, and a 10-day survival study was performed. Cold-inducible RNA-binding protein released into the circulation was significantly increased 24 h after hepatic I/R. Anti-CIRP antibody treatment markedly reduced hepatocellular damage markers and significantly improved the liver microarchitecture. Anti-CIRP also reduced the systemic and local inflammation demonstrated by attenuation in both serum and hepatic levels of interleukin 6. The expression of neutrophil-attracting chemokine as well as liver neutrophil infiltration was reduced by anti-CIRP treatment. Anti-CIRP also dramatically decreased the amount of apoptosis and nitrosative stress, evidenced by decrease in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining and inducible nitric oxide synthase and cyclooxygenase 2 levels, respectively. Finally, the 10-day survival rate was increased from 37.5% in the vehicle group to 75% in the anti-CIRP treatment group. Thus, targeting CIRP offers potential therapeutic implications in the treatment of hepatic I/R injury.
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Rodríguez A, Taurà P, García Domingo MI, Herrero E, Camps J, Forcada P, Sabaté S, Cugat E. Hepatic cytoprotective effect of ischemic and anesthetic preconditioning before liver resection when using intermittent vascular inflow occlusion: a randomized clinical trial. Surgery 2015; 157:249-59. [PMID: 25616941 DOI: 10.1016/j.surg.2014.09.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2014] [Accepted: 09/04/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Ischemic preconditioning (IPC) and anesthetic preconditioning (APC) have been reported to attenuate ischemia-reperfusion (IR) injury after liver resection under continuous inflow occlusion. This study evaluates whether these strategies enhance hepatic protection of remnant liver against IR after liver resection with intermittent clamping (INT). METHODS A total of 106 patients without underlying liver disease and submitted to liver resection using INT were randomized into 3 groups: IPC (10 minutes of inflow occlusion followed by 10 minutes of reperfusion before liver transection), APC (sevoflurane administration for 20 minutes before liver transection), and INT (no preconditioning). Patients were also stratified according to the extent of the hepatectomy. Cytoprotection was evaluated by comparing hepatocyte and endothelial dysfunction markers, apoptosis, histologic lesions, and postoperative outcome. RESULTS No differences were observed in preoperative chemotherapy and steatosis, total warm ischemia time, operative time, or blood loss. Kinetics of transaminases (aspartate aminotransferase, P = .137; alanine aminotransferase, P = .616), bilirubin (P = .980), and hyaluronic acid increase (P = .514) revealed no differences. Significant apoptosis was present in 40% of patients, mild-to-moderate leukocyte infiltration and steatosis in 45% and 55%, respectively, and mild sinusoidal congestion in 65%, with a similar distribution in the 3 groups. When patients were stratified by major versus minor resections, no differences were observed in any of the variables studied. Postoperative clinical outcomes were also similar. CONCLUSION These results suggest that these protocols of IPC and APC used in this study do not provide better cytoprotection from IR when INT is used.
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Affiliation(s)
- Aurora Rodríguez
- Department of Anesthesiology, Hospital Universitari Mútua Terrassa, Terrassa, Spain.
| | - Pilar Taurà
- Department of Anesthesiology, Liver Surgery and Liver Transplant Unit, Hospital Clinic, Barcelona University, Barcelona, Spain
| | - Maria I García Domingo
- Department of Surgery, Liver Surgery, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Eric Herrero
- Department of Surgery, Liver Surgery, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Judith Camps
- Department of Surgery, Liver Surgery, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Pilar Forcada
- Department of Histopathology, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Sergi Sabaté
- Department of Anesthesiology, Fundació Puigvert, Barcelona, Spain
| | - Esteve Cugat
- Department of Surgery, Liver Surgery, Hospital Universitari Mútua Terrassa, Terrassa, Spain
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Abstract
Understanding innate immune responses and their correlation to alloimmunity after solid organ transplantation is key to optimizing long term graft outcome. While Ischemia/Reperfusion injury (IRI) has been well studied, new insight into central mechanisms of innate immune activation, i.e. chemokine mediated cell trafficking and the role of Toll-like receptors have evolved recently. The mechanistic implications of Neutrophils, Macrophages/Monocytes, NK-cells, Dendritic cells in renal IRI has been proven by selective depletion of these cell types, thereby offering novel therapeutic interventions. At the same time, the multi-faceted role of different T-cell subsets in IRI has gained interest, highlighting the dichotomous effects of differentiated T-cells and suggesting more selective therapeutic approaches. Targeting innate immune cells and their activation and migration pathways, respectively, has been promising in experimental models holding translational potential. This review will summarize the effects of innate immune activation and potential strategies to interfere with the immunological cascade following renal IRI.
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