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Cui LL, Zhang L, Liu S, Zhu Q, Xue FS. Dexmedetomidine Cannot Attenuate Liver Injury and Improve Outcomes Following Laparoscopic Living Donor Hepatectomy: A Randomised Controlled Trial. Drug Des Devel Ther 2025; 19:4263-4274. [PMID: 40420947 PMCID: PMC12105671 DOI: 10.2147/dddt.s524343] [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: 02/22/2025] [Accepted: 05/15/2025] [Indexed: 05/28/2025] Open
Abstract
Purpose To determine the effects of intraoperative dexmedetomidine (DEX) administration on postoperative ischaemia/reperfusion injury (HIRI) and clinical outcomes of patients undergoing the laparoscopic living donor hepatectomy (LLDH). Patients and Methods Fifty-five patients who underwent the LLDH were randomly assigned to the DEX or control group. The DEX group received an intravenous infusion of DEX with an bolus dose of 1 µg/kg for 15 min before anaesthesia induction, followed by a continuous infusion at a rate of 0.4 µg/kg/h until the portal branch was disconnected. The control group was given an intravenous infusion of 0.9% saline at same volume and rate. The primary outcome was peak serum aspartate aminotransferase (AST) level during the first 72 h postoperatively. The secondary outcomes included other variables of postoperative liver and kidney function, intraoperative hemodynamic changes, postoperative recovery outcomes and the occurrence of complications. Results The peak serum AST level during the first 72 h postoperatively was not significantly different between groups (DEX vs control: 288 [194-466] vs 324 [194-437] IU/L; difference, -1.2 IU/L; 95% CI, -86.9 to 88.0; P=0.973). The intraoperative mean artery pressure was not significantly different, but intraoperative heart rate was significantly decreased in the DEX group. There were no significant differences between groups in other secondary outcomes. Conclusion This study demonstrates that intraoperative DEX administration at the studied dosage regimens cannot attenuate postoperative HIRI and does not improve clinical outcomes in patients undergoing the LLDH. Clinical Trial Registration www.chictr.org.cn, ChiCTR2000040629.
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Affiliation(s)
- Ling-Li Cui
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Liang Zhang
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Shen Liu
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Qian Zhu
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Fu-Shan Xue
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
- Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Fuzhou, People’s Republic of China
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Tao Y, Zhou W, Chen C, Zhang Q, Liu Z, Xia P, Ye Z, Li C. O-sialoglycoprotein Endopeptidase (OSGEP) Suppresses Hepatic Ischemia-Reperfusion Injury-Induced Ferroptosis Through Modulating the MEK/ERK Signaling Pathway. Mol Biotechnol 2025; 67:689-704. [PMID: 38456959 PMCID: PMC11711258 DOI: 10.1007/s12033-024-01084-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 01/16/2024] [Indexed: 03/09/2024]
Abstract
Hepatic ischemia-reperfusion injury (HIRI) was widely accepted as a critical complication of liver resection and transplantation. A growing body of evidence suggested that O-sialoglycoprotein endopeptidase (OSGEP) was involved in cell proliferation and mitochondrial metabolism. However, whether OSGEP could mediate the pathogenesis of HIRI has still remained unclarified. This study investigated whether OSGEP could be protective against HIRI and elucidated the potential mechanisms. The OSGEP expression level was detected in cases undergoing ischemia-related hepatectomy and a stable oxygen-glucose deprivation/reoxygenation (OGD/R) condition in hepG2 cells. Additionally, it was attempted to establish a mouse model of HIRI, thus, the function and mechanism of OSGEP could be analyzed. At one day after hepatectomy, the negative association of OSGEP expression level with the elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was noted. Moreover, it was attempted to carry out gain- and loss-of-function analyses of OSGEP in hepG2 cells to reveal its influences on OGD/R-induced injury and relevant signaling pathways. The findings suggested that OSGEP overexpression significantly protected hepG2 cells against ferroptotic cell death, while OSGEP consumption had opposite effects. Consistent with in vitro studies, OSGEP deficiency exacerbated liver functions and ferroptotic cell death in a mouse model of HIRI. The results also revealed that OSGEP mediated the progression of HIRI by regulating the MEK/ERK signaling pathway. Rescue experiments indicated that ERK1/2 knockdown or overexpression reversed the effects of OSGEP overexpression or knockdown on hepG2 cells under OGD/R condition. Taken together, the findings demonstrated that OSGEP could contribute to alleviate HIRI by mediating the MEK-ERK signaling pathway, which may serve as a potential prognostic marker and a therapeutic target for HIRI.
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Affiliation(s)
- Yuanyuan Tao
- Department of Anesthesiology, Xiangya Hospital of Central South University, Hunan Province, Changsha, 410008, China
| | - Wanqing Zhou
- Department of Anesthesiology, Xiangya Hospital of Central South University, Hunan Province, Changsha, 410008, China
| | - Cheng Chen
- Department of Anesthesiology, Xiangya Hospital of Central South University, Hunan Province, Changsha, 410008, China
| | - Qian Zhang
- Department of Anesthesiology, Xiangya Hospital of Central South University, Hunan Province, Changsha, 410008, China
| | - Zhuoyi Liu
- Department of Anesthesiology, Xiangya Hospital of Central South University, Hunan Province, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Central South University, Hunan Province, Changsha, China
| | - Pingping Xia
- Department of Anesthesiology, Xiangya Hospital of Central South University, Hunan Province, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Central South University, Hunan Province, Changsha, China
| | - Zhi Ye
- Department of Anesthesiology, Xiangya Hospital of Central South University, Hunan Province, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Central South University, Hunan Province, Changsha, China
| | - Chunling Li
- Department of Anesthesiology, Xiangya Hospital of Central South University, Hunan Province, Changsha, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Central South University, Hunan Province, Changsha, China.
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Li S, Xiang A, Guo F, Alarfaj AA, Gao Z. Fangchinoline protects hepatic ischemia/reperfusion liver injury in rats through anti-oxidative stress and anti-inflammation properties: an in silico study. Biotechnol Appl Biochem 2024; 71:1281-1292. [PMID: 38984607 DOI: 10.1002/bab.2628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 05/31/2024] [Indexed: 07/11/2024]
Abstract
Liver ischemia-reperfusion (I/R) injury is a common cause of organ failure, developed by a sudden block in the blood and oxygen supply and subsequent restoration. I/R damage is responsible for acute and chronic rejection after organ transplantation, accounting for 10% of early graft failure. The study investigated the therapeutic properties of fangchinoline in liver injury-induced rats. The rats were divided into three groups: Sham, I/R without pretreatment, and I/R + 10 mg/kg fangchinoline pretreatment. Blood and liver samples were collected for assays, and an in silico docking analysis was conducted to determine fangchinoline's inhibitory effect. The pretreatment with 10 mg/kg of fangchinoline effectively reduced hepatic marker enzymes such as AST, LDH, and ALT in the serum of rats with liver I/R damage. Fangchinoline treatment significantly reduced interleukin-8 (IL-8), IL-6, and tumor necrosis factor-α (TNF-α) in I/R-induced rats, boosting antioxidants and decreasing MDA. Histopathological studies showed liver injury protection, and fangchinoline inhibited TNF-α and IL-6 with improved binding affinity. Fangchinoline has hepatoprotective properties by reducing inflammation in rats with liver I/R damage, as demonstrated in the current study. Hence, it can be an effective salutary agent in preventing liver damage caused by I/R.
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Affiliation(s)
- Shuangxi Li
- Hepatopancreatobiliary Surgery Department, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - AnDong Xiang
- Second Department of General Surgery, The Affiliated Hospital of Yunnan University, Kunming, China
| | - Feng Guo
- Clinical Skills Training Center, Kunming Medical University, Kunming, Yunnan, China
| | - Abdullah A Alarfaj
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Zehai Gao
- Second Department of General Surgery, The Affiliated Hospital of Yunnan University, Kunming, China
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4
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Koh A, Wong T, Adiamah A, Sanyal S. Systematic review and meta-analysis of the effect of N-acetylcysteine on outcomes after liver resection. ANZ J Surg 2024; 94:1693-1701. [PMID: 39101362 DOI: 10.1111/ans.19183] [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: 04/19/2024] [Revised: 06/13/2024] [Accepted: 07/17/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND N-Acetylcysteine (NAC) is a recognized antioxidative agent that facilitates the conjugation of toxic metabolites. In recent years, NAC has been routinely used to limit ischaemia-reperfusion injury in liver transplantation. There remains, however, contradictory evidence on its effectiveness in liver resection. This meta-analysis examines the effectiveness of NAC in improving outcomes following hepatectomy. METHODS A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases was performed to identify relevant randomized controlled trials (RCTs) published since database inception until November 2023. The outcomes of Day 1 biochemical markers (lactate, ALT, bilirubin, and INR), length of stay, transfusion rates, and morbidity were extracted. Quantitative pooling of data was based on a random-effects model. The study protocol was registered on PROSPERO (Registration no: CRD42023442429). RESULTS Five RCTs reporting on 388 patients undergoing hepatectomy were included in the analysis. There were no significant differences in patient demographics between groups. Post-operative lactate was lower in patients receiving NAC (WMD -0.61, 95% CI -1.19 to -0.04, I2 = 67%). There were, however, no differences in the post-operative INR (WMD -0.04, 95% CI -0.19 to 0.12, I2 = 96%) and ALT (WMD -94.94, 95% CI -228.46 to 40.38; I2 = 67%). More importantly, there were no statistically significant differences in length of stay, transfusion rates, and morbidity between the two groups. CONCLUSION The administration of NAC in liver resection did not alter important biochemical parameters suggesting any real effectiveness in reducing hepatic dysfunction. There were no improvements in the clinical outcomes of length of stay, transfusion rates, and overall morbidity.
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Affiliation(s)
- Amanda Koh
- Gastrointestinal Surgery, Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK
| | - Tiffany Wong
- Gastrointestinal Surgery, Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK
| | - Alfred Adiamah
- Gastrointestinal Surgery, Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK
| | - Sudip Sanyal
- Gastrointestinal Surgery, Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK
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Wilson PR, Bridges KH, Scofield M, Wilson SH. Perioperative N-acetylcysteine: evidence and indications. Pain Manag 2024; 14:385-396. [PMID: 39166871 PMCID: PMC11486111 DOI: 10.1080/17581869.2024.2388504] [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: 05/10/2024] [Accepted: 07/31/2024] [Indexed: 08/23/2024] Open
Abstract
Nonopioid analgesics serve to improve analgesia and limit side effects and risks of perioperative opioids. N-acetylcysteine (NAC), the primary treatment of acetaminophen toxicity, may have perioperative indications, including analgesia. NAC impacts glutathione synthesis, oxidant scavenging, glutamate receptor modulation and neuroinflammation. Potential perioperative benefits include arrhythmia prevention after cardiac surgery, decreased contrast-induced nephropathy, improved post-transplant liver function and superior pulmonary outcomes with general anesthesia. NAC may improve perioperative analgesia, with some studies displaying a reduction in postoperative opioid use. NAC is generally well tolerated with an established safety profile. NAC administration may predispose to gastrointestinal effects, while parenteral administration may carry a risk of anaphylactoid reactions, including bronchospasm. Larger randomized trials may clarify the impact of NAC on perioperative analgesic outcomes.
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Affiliation(s)
- Phillip Ryan Wilson
- Department of Anesthesia & Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Kathryn H Bridges
- Department of Anesthesia & Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Michael Scofield
- Department of Anesthesia & Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Sylvia H Wilson
- Department of Anesthesia & Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
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Zhong F, Yang H, Peng X, Zeng K. Effects of perioperative steroid use on surgical stress and prognosis in patients undergoing hepatectomy: a systematic review and meta-analysis of randomized controlled trials. Front Pharmacol 2024; 15:1415011. [PMID: 39281283 PMCID: PMC11393686 DOI: 10.3389/fphar.2024.1415011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 07/29/2024] [Indexed: 09/18/2024] Open
Abstract
The objective of this study was to evaluate the clinical effects of perioperative steroid hormone usage in hepatectomy patients through a comprehensive systematic review and meta-analysis. Prospective randomized controlled trials (RCTs) investigating the perioperative use of steroid hormones in hepatectomy patients were systematically searched using various databases, including PubMed, Medline, Embase, the Cochrane Library, the Chinese Biomedical Literature Database, Wanfang Data, and the CNKI database. Two researchers independently screened and extracted data from selected studies. Data analysis was performed using RevMan 5.3 software. The results revealed significantly lower levels of total bilirubin (standard mean difference [SMD] = -0.7; 95% CI: -1.23 to -0.18; and p = 0.009), interleukin-6 (SMD = -1.02; 95% CI: -1.27 to -0.77; and p < 0.001), and C-reactive protein (SMD = -0 .65; 95% CI: -1 .18 to -0.11; and p = 0.02) on postoperative day 1 (POD 1), as well as a reduced incidence of postoperative complications in the steroid group compared to the placebo group. No significant differences were observed between the two groups regarding alanine aminotransferase (ALT) levels, aspartic aminotransferase (AST) levels, or specific complications such as intra-abdominal infection (p = 0.72), wound infection (p = 0.1), pleural effusion (p = 0.43), bile leakage (p = 0.66), and liver failure (p = 0.16). The meta-analysis results indicate that perioperative steroid usage can effectively alleviate liver function impairment and inflammation response following hepatectomy while improving patient prognosis.
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Affiliation(s)
- Furui Zhong
- Department of General Surgery, Zigong Fourth People's Hospital, Zigong, Sichuan, China
| | - Hua Yang
- Department of General Surgery, Zigong Fourth People's Hospital, Zigong, Sichuan, China
| | - Xuefeng Peng
- Department of General Surgery, Zigong Fourth People's Hospital, Zigong, Sichuan, China
| | - Kerui Zeng
- Department of General Surgery, Zigong Fourth People's Hospital, Zigong, Sichuan, China
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7
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Turan C, Kovács EH, Szabó L, Atakan I, Dembrovszky F, Ocskay K, Váncsa S, Hegyi P, Zubek L, Molnár Z. The Effect of Preoperative Administration of Glucocorticoids on the Postoperative Complication Rate in Liver Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med 2024; 13:2097. [PMID: 38610862 PMCID: PMC11012757 DOI: 10.3390/jcm13072097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 03/16/2024] [Accepted: 03/27/2024] [Indexed: 04/14/2024] Open
Abstract
Background: Glucocorticoids may grant a protective effect against postoperative complications. The evidence on their efficacy, however, has been inconclusive thus far. We investigated the effects of preoperatively administered glucocorticoids on the overall postoperative complication rate, and on liver function recovery in patients undergoing major liver surgery. Methods: We performed a systematic literature search on PubMed, Embase, and CENTRAL in October 2021, and repeated the search in April 2023. Pre-study protocol was registered on PROSPERO (ID: CRD42021284559). Studies investigating patients undergoing liver resections or transplantation who were administered glucocorticoids preoperatively and reported postoperative complications were eligible. Meta-analyses were performed using META and DMETAR packages in R with a random effects model. Risk of bias was assessed using RoB2. Results: The selection yielded 11 eligible randomized controlled trials (RCTs) with 964 patients. Data from nine RCTs (n = 837) revealed a tendency toward a lower overall complication rate with glucocorticoid administration (odds ratio: 0.71; 95% confidence interval: 0.38-1.31, p = 0.23), but it was not statistically significant. Data pooled from seven RCTs showed a significant reduction in wound infections with glucocorticoid administration [odds ratio: 0.64; 95% confidence interval: 0.45-0.92 p = 0.02]. Due to limited data availability, meta-analysis of liver function recovery parameters was not possible. Conclusions: The preoperative administration of glucocorticoids did not significantly reduce the overall postoperative complication rate. Future clinical trials should investigate homogenous patient populations with a specific focus on postoperative liver recovery.
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Affiliation(s)
- Caner Turan
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary
| | - Emőke Henrietta Kovács
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary
- Selye János Doctoral College for Advanced Studies, Semmelweis University, 1085 Budapest, Hungary
| | - László Szabó
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, 7623 Pécs, Hungary
| | - Işıl Atakan
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
| | - Fanni Dembrovszky
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, 7623 Pécs, Hungary
| | - Klementina Ocskay
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, 7623 Pécs, Hungary
| | - Szilárd Váncsa
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, 7623 Pécs, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, 7623 Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, 1085 Budapest, Hungary
| | - László Zubek
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary
| | - Zsolt Molnár
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary
- Department of Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, 61-701 Poznan, Poland
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8
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Ma X, Pan B, Wang L, Feng Z, Peng C. Network pharmacology and molecular docking elucidate potential mechanisms of Eucommia ulmoides in hepatic ischemia-reperfusion injury. Sci Rep 2023; 13:20716. [PMID: 38001230 PMCID: PMC10673959 DOI: 10.1038/s41598-023-47918-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 11/20/2023] [Indexed: 11/26/2023] Open
Abstract
Eucommia ulmoides (EU) and its diverse extracts have demonstrated antioxidative, anti-inflammatory, and cytoprotective properties against hepatic ischemia-reperfusion injury (HIRI). However, the primary constituents of EU and their putative mechanisms remain elusive. This study aims to explore the potential mechanisms of EU in the prevention and treatment of HIRI by employing network pharmacology and molecular docking methodologies. The main components and corresponding protein targets of EU were searched in the literature and TCMSP, and the compound target network was constructed by Cytoscape 3.9.1. Liver ischemia-reperfusion injury targets were searched in OMIM and GeneCards databases. The intersection points of compound targets and disease targets were obtained, and the overlapping targets were imported into the STRING database to construct the PPI network. We further analyzed the targets for GO and KEGG enrichment. Finally, molecular docking studies were performed on the core targets and active compounds. The component-target network unveiled a total of 26 efficacious bioactive compounds corresponding to 207 target proteins. Notably, the top-ranking compounds based on degree centrality were quercetin, β-sitosterol, and gallic acid. Within the PPI network, the highest degree centrality encompassed RELA, AKT1, TP53. GO and KEGG enrichment analysis elucidated that EU in HIRI primarily engaged in positive regulation of gene expression, positive transcriptional regulation via RNA polymerase II promoter, negative modulation of apoptotic processes, positive regulation of transcription from DNA templates, and drug responsiveness, among other biological processes. Key pathways included cancer pathways, RAGE signaling pathway, lipid metabolism, atherosclerosis, TNF signaling pathway, PI3K-Akt signaling pathway, and apoptotic pathways. Molecular docking analysis revealed robust affinities between quercetin, β-sitosterol, gallic acid, and RELA, AKT1, TP53, respectively. This study reveals EU exhibits substantial potential in mitigating and treating HIRI through multifaceted targeting and involvement in intricate signaling pathways.
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Affiliation(s)
- Xuan Ma
- Department of General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Bochen Pan
- Department of Biochemistry and Molecular Biology, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Liusong Wang
- Department of General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Zanjie Feng
- Clinical Medical Research Center, The affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
| | - Cijun Peng
- Department of Hepatobiliary Surgery, The affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
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9
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Felli E, Felli E, Muttillo EM, Urade T, Laracca GG, Giannelli V, Famularo S, Geny B, Ettorre GM, Rombouts K, Pinzani M, Diana M, Gracia-Sancho J. Liver ischemia-reperfusion injury: From trigger loading to shot firing. Liver Transpl 2023; 29:1226-1233. [PMID: 37728488 DOI: 10.1097/lvt.0000000000000252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 08/15/2023] [Indexed: 09/21/2023]
Abstract
An ischemia-reperfusion injury (IRI) results from a prolonged ischemic insult followed by the restoration of blood perfusion, being a common cause of morbidity and mortality, especially in liver transplantation. At the maximum of the potential damage, IRI is characterized by 2 main phases. The first is the ischemic phase, where the hypoxia and vascular stasis induces cell damage and the accumulation of damage-associated molecular patterns and cytokines. The second is the reperfusion phase, where the local sterile inflammatory response driven by innate immunity leads to a massive cell death and impaired liver functionality. The ischemic time becomes crucial in patients with underlying pathophysiological conditions. It is possible to compare this process to a shooting gun, where the loading trigger is the ischemia period and the firing shot is the reperfusion phase. In this optic, this article aims at reviewing the main ischemic events following the phases of the surgical timeline, considering the consequent reperfusion damage.
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Affiliation(s)
- Eric Felli
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
| | - Emanuele Felli
- Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, France
| | - Edoardo M Muttillo
- Department of Medical Surgical Science and Translational Medicine, Sant' Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Takeshi Urade
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Japan
| | - Giovanni G Laracca
- Department of Medical Surgical Science and Translational Medicine, Sant' Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Valerio Giannelli
- Department of Transplantation and General Surgery, San Camillo Hospital, Italy
| | - Simone Famularo
- Department of Biomedical Science, Humanitas University Pieve Emanuele, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Research Institute Against Cancer of the Digestive System (IRCAD), France
| | - Bernard Geny
- Institute of Physiology, EA3072 Mitochondria Respiration and Oxidative Stress, University of Strasbourg, France
| | - Giuseppe M Ettorre
- Department of Transplantation and General Surgery, San Camillo Hospital, Italy
| | - Krista Rombouts
- University College London - Institute for Liver and Digestive Health, Royal Free Hospital, NW3 2PF London, United Kingdom
| | - Massimo Pinzani
- University College London - Institute for Liver and Digestive Health, Royal Free Hospital, NW3 2PF London, United Kingdom
| | - Michele Diana
- Research Institute Against Cancer of the Digestive System (IRCAD), France
| | - Jordi Gracia-Sancho
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
- Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, Hospital Clínic Barcelona, CIBEREHD, Barcelona, Spain
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10
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Geng Y, Xie Y, Li W, Mou Y, Chen F, Xiao J, Liao X, Hu X, Ji J, Ma L. Toward the bioactive potential of myricitrin in food production: state-of-the-art green extraction and trends in biosynthesis. Crit Rev Food Sci Nutr 2023; 64:10668-10694. [PMID: 37395263 DOI: 10.1080/10408398.2023.2227262] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Abstract
Myricitrin is a member of flavonols, natural phenolic compounds extracted from plant resources. It has gained great attention for various biological activities, such as anti-inflammatory, anti-cancer, anti-diabetic, as well as cardio-/neuro-/hepatoprotective activities. These effects have been demonstrated in both in vitro and in vivo models, making myricitrin a favorable candidate for the exploitation of novel functional foods with potential protective or preventive effects against diseases. This review summarized the health benefits of myricitrin and attempted to uncover its action mechanism, expecting to provide a theoretical basis for their application. Despite enormous bioactive potential of myricitrin, low production, high cost, and environmental damage caused by extracting it from plant resources greatly constrain its practical application. Fortunately, innovative, green, and sustainable extraction techniques are emerging to extract myricitrin, which function as alternatives to conventional techniques. Additionally, biosynthesis based on synthetic biology plays an essential role in industrial-scale manufacturing, which has not been reported for myricitrin exclusively. The construction of microbial cell factories is absolutely an appealing and competitive option to produce myricitrin in large-scale manufacturing. Consequently, state-of-the-art green extraction techniques and trends in biosynthesis were reviewed and discussed to endow an innovative perspective for the large-scale production of myricitrin.
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Affiliation(s)
- Yaqian Geng
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China
| | - Yingfeng Xie
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China
| | - Wei Li
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China
| | - Yao Mou
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China
| | - Fang Chen
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, Ourense, Spain
| | - Xiaojun Liao
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China
| | - Xiaosong Hu
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China
| | - Junfu Ji
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China
| | - Lingjun Ma
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China
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11
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Yan X, Huang S, Li F, Jiang L, Jiang Y, Liu J. Short-term outcomes of perioperative glucocorticoid administration in patients undergoing liver surgery: a systematic review and meta-analysis of randomised controlled trials. BMJ Open 2023; 13:e068969. [PMID: 37169506 DOI: 10.1136/bmjopen-2022-068969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/13/2023] Open
Abstract
OBJECTIVE The purpose of this systematic review and meta-analysis was to investigate whether glucocorticoid might be beneficial after hepatectomy. DESIGN Systematic review and meta-analysis. DATA SOURCES PubMed, Embase, Cochrane Library and Web of Science. ELIGIBILITY CRITERIA We included studies assessing the efficacy of perioperative glucocorticoid administration in patients undergoing liver surgery. DATA EXTRACTION AND SYNTHESIS Four data bases were retrieved for all randomised controlled trials. We considered postoperative complications, hospital stay and postoperative chemistry evaluations as outcomes. Pooled effects of dichotomic variables were expressed as relative risk (RR) with a 95% CI. The mean difference was used for continuous variables and an inverse variance statistical method was adopted. RESULTS Fourteen studies with 1205 patients were included. Lower risk of overall complications was associated with glucocorticoid (RR, 0.77; 95% CI 0.64 to 0.92), while no difference was found in hospital stay (RR, 0.02; 95% CI -0.47 to 0.51). There were also improvements in postoperative chemistry evaluations including interleukin 6 on day 1 and 3, C reactive protein on day 1, 2 and 3, international normalised ratio on day 2, total bilirubin on day 1, 2, 3 and 5, albumin on day 1. CONCLUSION Current evidence indicated that perioperative glucocorticoid administration for patients undergoing hepatectomy reduced the risk of overall complications with inhibited postoperative inflammatory response and improved postoperative liver function. PROSPERO REGISTRATION NUMBER CRD42022307533.
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Affiliation(s)
- Xiangyu Yan
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Songhan Huang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Feiyu Li
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Liyong Jiang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yong Jiang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jun Liu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital affliated to Shandong First Medical University, Jinan, China
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12
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Liu L, Zhang C, Lu T, Li X, Jiang Z, Tian H, Hao X, Yang K, Guo T. The efficacy and safety of glucocorticoid for perioperative patients with hepatectomy: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2023; 17:59-71. [PMID: 36576056 DOI: 10.1080/17474124.2023.2162878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Glucocorticoids have been used in patients undergoing perioperative hepatectomy, however their safety and efficacy remain controversial. This meta-analysis was conducted to investigate this issue and further provide reference for clinical practice. METHODS PubMed/MEDLINE, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) from database inception to December 2022. Literature screening and data extraction were performed independently by two reviewers. The methodological quality of the RCTs was assessed using the Jadad scale. RevMan 5.4 was used for the meta-analysis. RESULTS A total of 11 RCTs involving 905 patients were included. Compared with the control group, we found perioperative glucocorticoid administration significantly lowered overall complication rate [RR = 0.67; 95% CI (0.55, 0.83); P = 0.0003], infectious complication rate [RR = 0.41; 95% CI (0.21, 0.82); P = 0.01] and postoperative liver failure [RR = 0.63; 95% CI (0.41, 0.97); P = 0.03]. In addition, glucocorticoids appear to improve liver function (TBil) [MD = -0.36, 95% CI (-0.59, -0.14), P = 0.001] and reduce the release of certain inflammatory cytokines (IL-6) [MD = -48.52, 95% CI (-56.88, -40.16), P < 0.00001]. CONCLUSION Based on the available evidence, glucocorticoids appear to be safe and effective in patients undergoing hepatectomy, but further research is needed.
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Affiliation(s)
- Lili Liu
- The First Clinical Medicine College, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.,Department of General Surgery, Gansu Provincial People's Hospital, Lanzhou, Gansu, China
| | - Chengren Zhang
- Department of General Surgery, Gansu Provincial People's Hospital, Lanzhou, Gansu, China.,General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Tingting Lu
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.,Institution of Clinical Research and Evidence Based Medicine, Gansu Provincial People's Hospital, Lanzhou, Gansu, China
| | - Xiong Li
- Department of General Surgery, Gansu Provincial People's Hospital, Lanzhou, Gansu, China.,General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Zhiliang Jiang
- The First Clinical Medicine College, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.,Department of General Surgery, Gansu Provincial People's Hospital, Lanzhou, Gansu, China
| | - Hongwei Tian
- Department of General Surgery, Gansu Provincial People's Hospital, Lanzhou, Gansu, China
| | - Xiangyong Hao
- Department of General Surgery, Gansu Provincial People's Hospital, Lanzhou, Gansu, China
| | - Kehu Yang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.,Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou, Gansu, China
| | - Tiankang Guo
- The First Clinical Medicine College, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.,Department of General Surgery, Gansu Provincial People's Hospital, Lanzhou, Gansu, China
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13
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Piao C, Sang J, Kou Z, Wang Y, Liu T, Lu X, Jiao Z, Wang H. Effects of Exosomes Derived from Adipose-Derived Mesenchymal Stem Cells on Pyroptosis and Regeneration of Injured Liver. Int J Mol Sci 2022; 23:12065. [PMID: 36292924 PMCID: PMC9602906 DOI: 10.3390/ijms232012065] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 09/29/2022] [Accepted: 10/06/2022] [Indexed: 09/01/2023] Open
Abstract
Although accumulating evidence indicates that exosomes have a positive therapeutic effect on hepatic ischemia-reperfusion injury (HIRI), studies focusing on the alleviation of liver injury by exosomes derived from adipose-derived mesenchymal stem cells (ADSCs-Exo) based on the inhibition of cell pyroptosis have not yet been reported. Exosomes contain different kinds of biologically active substances such as proteins, lipids, mRNAs, miRNAs, and signaling molecules. These molecules are widely involved in cell-cell communication, cell signal transmission, proliferation, migration, and apoptosis. Therefore, we investigated the positive effects exerted by ADSCs-Exo after hepatic ischemia-reperfusion with partial resection injury in rats. In this study, we found that the post-operative tail vein injection of ADSCs-Exo could effectively inhibit the expression of pyroptosis-related factors such as NLRP3, ASC, caspase-1, and GSDMD-N, and promote the expression of regeneration-related factors such as Cyclin D1 and VEGF. Moreover, we found that the above cellular activities were associated with the NF-κB and Wnt/β-catenin signaling pathways. According to the results, ADSCs and ADSCs-Exo can reduce pyroptosis in the injured liver and promote the expression of those factors related to liver regeneration, while they can inhibit the NF-κB pathway and activate the Wnt/β-catenin pathway. However, although adipose-derived mesenchymal stem cell (ADSC) transplantation can reduce liver injury, it leads to a significant increase in the pyroptosis-related protein GSDMD-N expression. In conclusion, our study shows that ADSCs-Exo has unique advantages and significance as a cell-free therapy to replace stem cells and still has a broad research prospect in the clinical diagnosis and treatment of liver injuries.
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Affiliation(s)
- Chenxi Piao
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
| | - Jinfang Sang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
| | - Zhipeng Kou
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
| | - Yue Wang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
| | - Tao Liu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
| | - Xiangyu Lu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
| | - Zhihui Jiao
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150030, China
| | - Hongbin Wang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
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14
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Nejati M, Dehghan P, Jamilian P, Zarezadeh M. The effects of N-acetylcysteine on recovery biomarkers: A systematic review and meta-analysis of controlled trials. J Food Biochem 2022; 46:e14116. [PMID: 35261035 DOI: 10.1111/jfbc.14116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 02/04/2022] [Accepted: 02/07/2022] [Indexed: 11/30/2022]
Abstract
N-acetylcysteine (NAC) is one of the antioxidant supplements which is thought to improve recovery. Existing studies regarding NAC and recovery presented conflicting results. This systematic review and meta-analysis evaluated the existing trials and determined the efficacy of acute and chronic NAC administration on recovery biomarkers. PubMed, Web of Science, and Scopus were searched up to July 2021. The random effects or fixed effects model was applied in the meta-analysis. Sensitivity and subgroup analyses were performed. In case of the presence of publication bias, standard methods were applied. The meta-analysis comprised 37 papers (1,388 participants). All included studies were in English language. Acute NAC administration indicated no significant effects on lactate, pH, VO2 , and CPK-MB ([SMD = -0.06 mmol/L; 95% CI: -0.40, 0.28; p = .714], [SMD = 0.17; 95% CI: -0.28, 0.62; p = .454], [SMD = -0.11 L/min; 95% CI: -0.63, 0.41; p = .686], and [SMD = -0.19 units/L; 95% CI: -0.62, 0.24; p = .395]). Additionally, no evidence of significant influence of chronic NAC administration on lactate, pH, VO2 , and CK was revealed ([SMD = 0.01 mmol/L; 95% CI: -0.25, 0.27; p = .950], [SMD = -0.51; 95% CI: -1.73, 0.70; p = .424], [SMD = -0.18 L/min; 95% CI: -0.56, 0.20; p = .361], and [SMD = -0.04 units/L; 95% CI: -0.36, 0.29; p = .821]). No considerable effect of NAC on recovery was found. PRACTICAL APPLICATIONS: Previous studies on the influence of NAC administration on recovery biomarkers have presented conflicting results. This systematic review and meta-analysis offers a broad range of detailed information on the influence of chronic and acute NAC supplementation outcomes regarding recovery biomarkers. Overall, the results support that NAC supplementation may not be effective in improving recovery biomarkers. However, subgroup analyses based on NAC dosage indicated the meaningful effect of NAC on CK-MB at the dosage of ≥100 mg/kg.
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Affiliation(s)
- Marzieh Nejati
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.,Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parvin Dehghan
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parsa Jamilian
- Keele Medical School, Keele University, Staffordshire, UK
| | - Meysam Zarezadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Clinical Nutrition, School of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
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15
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Ntamo Y, Ziqubu K, Chellan N, Nkambule BB, Nyambuya TM, Mazibuko-Mbeje SE, Gabuza KB, Orlando P, Tiano L, Dludla PV. Clinical use of N-acetyl cysteine during liver transplantation: Implications of oxidative stress and inflammation as therapeutic targets. Biomed Pharmacother 2022; 147:112638. [DOI: 10.1016/j.biopha.2022.112638] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/05/2022] [Accepted: 01/12/2022] [Indexed: 02/09/2023] Open
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16
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Mao XL, Cai Y, Chen YH, Wang Y, Jiang XX, Ye LP, Li SW. Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury. Front Med (Lausanne) 2022; 8:757336. [PMID: 35059411 PMCID: PMC8764312 DOI: 10.3389/fmed.2021.757336] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 12/08/2021] [Indexed: 12/16/2022] Open
Abstract
Hepatic ischemia reperfusion injury (IRI), a fascinating topic that has drawn a lot of interest in the last few years, is a major complication caused by a variety of clinical situations, such as liver transplantation, severe trauma, vascular surgery, and hemorrhagic shock. The IRI process involves a series of complex events, including mitochondrial deenergization, metabolic acidosis, adenosine-5'-triphosphate depletion, Kupffer cell activation, calcium overload, oxidative stress, and the upregulation of pro-inflammatory cytokine signal transduction. A number of protective strategies have been reported to ameliorate IRI, including pharmacological therapy, ischemic pre-conditioning, ischemic post-conditioning, and machine reperfusion. However, most of these strategies are only at the stage of animal model research at present, and the potential mechanisms and exact therapeutic targets have yet to be clarified. IRI remains a main cause of postoperative liver dysfunction, often leading to postoperative morbidity or even mortality. Very recently, it was reported that the activation of peroxisome proliferator-activated receptor γ (PPARγ), a member of a superfamily of nuclear transcription factors activated by agonists, can attenuate IRI in the liver, and FAM3A has been confirmed to mediate the protective effect of PPARγ in hepatic IRI. In addition, non-coding RNAs, like LncRNAs and miRNAs, have also been reported to play a pivotal role in the liver IRI process. In this review, we presented an overview of the latest advances of treatment strategies and proposed potential mechanisms behind liver IRI. We also highlighted the role of several important molecules (PPARγ, FAM3A, and non-coding RNAs) in protecting against hepatic IRI. Only after achieving a comprehensive understanding of potential mechanisms and targets behind IRI can we effectively ameliorate IRI in the liver and achieve better therapeutic effects.
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Affiliation(s)
- Xin-Li Mao
- Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Institute of Digestive Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Yue Cai
- Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Institute of Digestive Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Ya-Hong Chen
- Health Management Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Yi Wang
- Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Institute of Digestive Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Xiu-Xiu Jiang
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Li-Ping Ye
- Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Institute of Digestive Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Shao-Wei Li
- Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.,Institute of Digestive Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
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17
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Kuan LL, Dennison AR, Garcea G. Outcomes of peri-operative glucocorticosteroid use in major pancreatic resections: a systematic review. HPB (Oxford) 2021; 23:1789-1798. [PMID: 34593313 DOI: 10.1016/j.hpb.2021.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 07/12/2021] [Accepted: 07/12/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND There is increasing evidence that peri-operative glucocorticosteroid can ameliorate the systemic response following major surgery. Preliminary evidence suggests peri-operative usage of glucocorticosteroid may decrease post-operative complications. These positive associations have been observed in a range of different operations including intra-abdominal, thoracic, cardiac, and orthopaedic surgery. This review aims to investigate the impact of peri-operative glucocorticosteroid in major pancreatic resections. METHODS A systematic review based on a search in Medline and Embase databases was performed. PRISMA guidelines for systematic reviews were followed. RESULTS A total of five studies were analysed; three randomised controlled trials and two retrospective cohort studies. The total patient population was 1042. The glucocorticosteroids used were intravenous hydrocortisone or dexamethasone. Three studies reported significantly lower morbidity in the peri-operative glucocorticosteroid group. The number needed to treat to prevent one major complication with hydrocortisone is four patients. Two studies demonstrated that dexamethasone was associated with a statistically significantly improved median overall survival in pancreatic cancer. CONCLUSION This is the first systematic review conducted to investigate the significance of peri-operative glucocorticosteroid in patients undergoing pancreatic resection. This review shows a correlation of positive outcomes with the administration of glucocorticosteroid in the peri-operative setting following a major pancreatic resection.. More randomised clinical trials are required to confirm if this is a true effect, as it would have significant implications.
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Affiliation(s)
- Li Lian Kuan
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom; Discipline of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
| | - Ashley R Dennison
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
| | - Giuseppe Garcea
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
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18
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de Klein GW, Brohet RM, Liem MSL, Klaase JM. Post-operative Day 1 Serum Transaminase Levels in Relation to Morbidity After Liver Resection. World J Surg 2021; 46:433-440. [PMID: 34797398 DOI: 10.1007/s00268-021-06280-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/31/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Post-operative serum transaminases have been proposed as possible early predictors of morbidity after liver resection. This study aimed to verify the clinical value of post-operative serum transaminases. METHODS Clinical data from 2001 to 2016 in a single non-academic referral HPB center were collected from a prospectively held database. Post-operative day 1 serum aspartate transaminase (AST) and alanine transaminase (ALT) were tested for their relationship with post-operative major morbidity, defined by a Clavien-Dindo score 3 or higher, and mortality. RESULTS For this analysis, 371 patients were included, including 149 (40%) undergoing major liver resections. In total, 17% of the patients developed major morbidity. Stepwise logistic regression demonstrated that AST, and not ALT, is an independent predictor for major morbidity (p = 0.017). The probability of major morbidity significantly increased with increasing AST values. A threshold value of 242 U/L was found to be predictive for one or more major complications. CONCLUSIONS In this study, post-operative serum AST on day 1 was a predictive factor for major morbidity after liver resection. For patients with low AST value, early discharge could be considered. However, because of the substantial inter-individual variability of AST values, more studies are needed to translate these results into clinical practice.
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Affiliation(s)
- G W de Klein
- Department of Surgery, Medisch Spectrum Twente, Koningsplein 1, 7512 KZ, Enschede, The Netherlands
| | - R M Brohet
- Department of Research and Innovation, Isala, Zwolle, Netherlands
| | - M S L Liem
- Department of Surgery, Medisch Spectrum Twente, Koningsplein 1, 7512 KZ, Enschede, The Netherlands
| | - J M Klaase
- Department of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, Groningen, Netherlands.
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19
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Niederwieser T, Braunwarth E, Dasari BVM, Pufal K, Szatmary P, Hackl H, Haselmann C, Connolly CE, Cardini B, Öfner D, Roberts K, Malik H, Stättner S, Primavesi F. Early postoperative arterial lactate concentrations to stratify risk of post-hepatectomy liver failure. Br J Surg 2021; 108:1360-1370. [PMID: 34694377 DOI: 10.1093/bjs/znab338] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 09/02/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Post-hepatectomy liver failure (PHLF) represents the major determinant for death after liver resection. Early recognition is essential. Perioperative lactate dynamics for risk assessment of PHLF and associated morbidity were evaluated. METHODS This was a multicentre observational study of patients undergoing hepatectomy with validation in international high-volume units. Receiver operating characteristics analysis and cut-off calculation for the predictive value of lactate for clinically relevant International Study Group of Liver Surgery grade B/C PHLF (clinically relevant PHLF (CR-PHLF)) were performed. Lactate and other perioperative factors were assessed in a multivariable CR-PHLF regression model. RESULTS The exploratory cohort comprised 509 patients. CR-PHLF, death, overall morbidity and severe morbidity occurred in 7.7, 3.3, 40.9 and 29.3 per cent of patients respectively. The areas under the curve (AUCs) regarding CR-PHLF were 0.829 (95 per cent c.i. 0.770 to 0.888) for maximum lactate within 24 h (Lactate_Max) and 0.870 (95 per cent c.i. 0.818 to 0.922) for postoperative day 1 levels (Lactate_POD1). The respective AUCs in the validation cohort (482 patients) were 0.812 and 0.751 and optimal Lactate_Max cut-offs were identical in both cohorts. Exploration cohort patients with Lactate_Max 50 mg/dl or greater more often developed CR-PHLF (50.0 per cent) than those with Lactate_Max between 20 and 49.9 mg/dl (7.4 per cent) or less than 20 mg/dl (0.5 per cent; P < 0.001). This also applied to death (18.4, 2.7 and 1.4 per cent), severe morbidity (71.1, 35.7 and 14.1 per cent) and associated complications such as acute kidney injury (26.3, 3.1 and 2.3 per cent) and haemorrhage (15.8, 3.1 and 1.4 per cent). These results were confirmed in the validation group. Combining Lactate_Max with Lactate_POD1 further increased AUC (ΔAUC = 0.053) utilizing lactate dynamics for risk assessment. Lactate_Max, major resections, age, cirrhosis and chronic kidney disease were independent risk factors for CR-PHLF. A freely available calculator facilitates clinical risk stratification (www.liver-calculator.com). CONCLUSION Early postoperative lactate values are powerful, readily available markers for CR-PHLF and associated complications after hepatectomy with potential for guiding postoperative care.Presented in part as an oral video abstract at the 2020 online Congress of the European Society for Surgical Research and the 2021 Congress of the Austrian Surgical Society.
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Affiliation(s)
- Thomas Niederwieser
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Eva Braunwarth
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Bobby V M Dasari
- Department of Hepatobiliary, Pancreatic and Transplant Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Kamil Pufal
- Department of Hepatobiliary, Pancreatic and Transplant Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Peter Szatmary
- Department of Hepato-Biliary Surgery, University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Hubert Hackl
- Institute of Bioinformatics, Biocentre, Medical University of Innsbruck, Innsbruck, Austria
| | - Clemens Haselmann
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Catherine E Connolly
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Keith Roberts
- Department of Hepatobiliary, Pancreatic and Transplant Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Hassan Malik
- Department of Hepato-Biliary Surgery, University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Stefan Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.,Department of General, Visceral and Vascular Surgery, Salzkammergut Klinikum, Vöcklabruck, Austria
| | - Florian Primavesi
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.,Department of Hepato-Biliary Surgery, University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.,Department of General, Visceral and Vascular Surgery, Salzkammergut Klinikum, Vöcklabruck, Austria
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20
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Hai HH, Aw P, Teng TZJ, Shelat VG. Perioperative steroid administration reduces overall complications in patients undergoing liver resection: A meta-analysis. World J Gastrointest Surg 2021; 13:1079-1094. [PMID: 34621482 PMCID: PMC8462075 DOI: 10.4240/wjgs.v13.i9.1079] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/03/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatic resection (HR) results in an inflammatory response that can be modified by perioperative steroid administration. However, it remains to be determined if this response's attenuation translates to a reduction in complications. AIM To evaluate if perioperative administration of steroids reduces complications following HR. METHODS A systematic review of randomized controlled trials (RCTs) was conducted on PubMed, Embase, and Cochrane Central Register of Controlled Trials to evaluate the effect of perioperative steroid (compared to placebo or no intervention) use in patients undergoing HR. Clinical outcomes were extracted, and meta-analysis was performed. RESULTS 8 RCTs including 590 patients were included. Perioperative steroid administration was associated with significant reduction in postoperative complications [odds ratios: 0.58; 95% confidence intervals (CI): 0.35-0.97, P = 0.04]. There was also improvement in biochemical and inflammatory markers, including serum bilirubin on postoperative day 1 [MD: -0.27; 95%CI: (-0.47, -0.06), P = 0.01], C-reactive protein on postoperative day 3 [MD: -4.89; 95%CI: (-5.83, -3.95), P < 0.001], and interleukin-6 on postoperative day 1 [MD: -54.84; 95%CI: (-63.91, -45.76), P < 0.001]. CONCLUSION Perioperative steroids administration in HR may reduce overall complications, postoperative bilirubin, and inflammation. Further studies are needed to determine the optimal dose and duration and patient selection.
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Affiliation(s)
- Hao-Han Hai
- NUS Yong Loo Lin School of Medicine, Singapore 119228, Singapore
| | - Phoebe Aw
- NUS Yong Loo Lin School of Medicine, Singapore 119228, Singapore
| | | | - Vishal G Shelat
- NTU Lee Kong Chian School of Medicine, Singapore 308232, Singapore
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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21
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Litvinova ES, Konoplya NN, Shulginova AA, Kharchenko AV. Proteins of allogeneic hepatocytes and pharmacological preparations for the correction of immunometabolic disorders in experimental liver pathology. RESEARCH RESULTS IN PHARMACOLOGY 2021. [DOI: 10.3897/rrpharmacology.7.70314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Introduction: The relationship of numerous metabolic shifts, disorders of hepatocytes functional activity resulting from hypoxia and toxic liver damage with the function of the immune system has not been sufficiently studied so far, nor have the most effective methods of pharmacological correction been established.
Materials and Methods: The studies were carried out on 603 mature male Wistar rats and 45 mice. Acute toxic liver damage (ATLD) was modeled by intramuscular introduction of carbon tetrachloride; acute liver ischemia (ALI) was caused by clamping the hepatoduodenal ligament for 20 minutes; chronic alcohol intoxication (CAI) was modeled by forced intragastric administration of 20% ethanol solution for 60 days. Isolation of xenogeneic (murine) and allogeneic (rat) hepatocytes from newborn mice and rats was carried out according to the method of Berry and Friend (1969); culture fluid of hepatocytes and its protein fractions were prepared according to our developed techniques. The obtained biological material was intraperitoneally introduced into the rats with ATLD, ALI, and CAI.
Results and Discussion: In all the models of the liver damage, there developed morphological and biochemical signs of the liver damage, impaired congenital and adaptive immunity, oxidative stress, increased lipid peroxidation processes.
Conclusion: The introduction of allogeneic hepatocytes, culture fluid obtained on their basis,and proteins isolated from it with MW less than 130 kDa to the recipients with toxic and ischemic liver damage more effectively corrects the pathologic changes in the liver in comparison with xenogeneic hepatocytes, their culture fluid and pharmacological preparations (combinations of Essentiale N and Hypoxenum or Heptral and Mexicor).
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22
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Krawczyk P, Morawski M, Krasnodębski M, Sieńko D, Grąt M, Kron P, Lodge P. Long-Term Effects of Pedicle Clamping during Major Hepatectomy for Colorectal Liver Metastases. J Clin Med 2021; 10:2778. [PMID: 34202824 PMCID: PMC8269320 DOI: 10.3390/jcm10132778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/16/2021] [Accepted: 06/20/2021] [Indexed: 11/17/2022] Open
Abstract
The use of the Pringle maneuver (PM) varies widely among surgical departments. Its use depends on the operator and type of liver resection. The aim of this study was to determine the impact of the PM on patient outcomes when undergoing major liver resections. This retrospective study comprised 179 colorectal liver metastasis patients from two liver centers from Leeds and Warsaw. Only right or right extended hepatectomies with negative oncological margins were included. The primary outcome measure was the 5-year overall survival (OS). The PM was applied during 60 (33.5%) major hepatectomies included in the study and was associated with a higher peak 3-day postoperative bilirubin concentration (p = 0.002), yet not with the peak 3-day alanine aminotransferase activity (p = 0.415). The 5-year OS after liver resections with the PM and without the PM were 55.0% and 33.4%, respectively (p = 0.019). Following stratification by the Tumor Burden Score, after resections with the use of the PM, superior survival was particularly found in the subgroup of patients at intermediate risk of recurrence (p = 0.004). However, the use of the PM had no significant effect on the 5-year overall survival following adjustment for the confounding effect of the carcinoembryonic antigen concentration (p = 0.265). The use of the PM had no negative effects on the long-term outcomes in patients undergoing major, oncologically radical liver resections for colorectal metastases.
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Affiliation(s)
- Piotr Krawczyk
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland; (P.K.); (M.K.); (D.S.); (M.G.)
| | - Marcin Morawski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland; (P.K.); (M.K.); (D.S.); (M.G.)
| | - Maciej Krasnodębski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland; (P.K.); (M.K.); (D.S.); (M.G.)
| | - Damian Sieńko
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland; (P.K.); (M.K.); (D.S.); (M.G.)
| | - Michał Grąt
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland; (P.K.); (M.K.); (D.S.); (M.G.)
| | - Philipp Kron
- Department of HPB and Transplant Surgery, St. James’ University Hospital, Leeds LS9 7TF, UK; (P.K.); (P.L.)
| | - Peter Lodge
- Department of HPB and Transplant Surgery, St. James’ University Hospital, Leeds LS9 7TF, UK; (P.K.); (P.L.)
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Pemafibrate Pretreatment Attenuates Apoptosis and Autophagy during Hepatic Ischemia-Reperfusion Injury by Modulating JAK2/STAT3 β/PPAR α Pathway. PPAR Res 2021; 2021:6632137. [PMID: 33777128 PMCID: PMC7972847 DOI: 10.1155/2021/6632137] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 03/01/2021] [Indexed: 11/18/2022] Open
Abstract
Hepatic ischemia-reperfusion injury (HIRI) is a common phenomenon in liver transplantation and liver surgery. This article is aimed at clarifying the role of pemafibrate in HIRI through JAK2/STAT3β/PPARα. In the experiment, we divided Balb/c into seven groups, namely, normal control (NC), Sham, PEM (1.0 mg/kg), IRI, IRI + PEM (0.1 mg/kg), IRI + PEM (0.5 mg/kg), and IRI + PEM (1.0 mg/kg). We used biochemical assay, histopathological evaluation, immunohistochemistry, RT-PCR and qRT-PCR, ELISA analysis, and other methods to determine the level of serum AST, ALT, IL-1β, and TNF-α in the liver at three time points (2 h, 8 h, and 24 h) after reperfusion of apoptosis factor, autophagy factor, and the JAK2/STAT3/PPARα content in tissues. Our experiment results showed that the pemafibrate can effectively reduce the level of hepatic IR injury. In addition, pemafibrate has anti-inflammatory, antiapoptotic, and antiautophagy effects, which are mediated by the JAK2/STAT3β/PPARα pathway.
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Shen Y, Shen X, Cheng Y, Liu Y. Myricitrin pretreatment ameliorates mouse liver ischemia reperfusion injury. Int Immunopharmacol 2020; 89:107005. [PMID: 33045574 DOI: 10.1016/j.intimp.2020.107005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 08/27/2020] [Accepted: 09/10/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Myricitrin has been reported to exert protective effects on liver diseases, but the protective effects of myricitrin against liver ischemia reperfusion (I/R) injury and the underlying mechanisms remain unexplored. This study aimed to investigate the effects of myricitrin on liver I/R injury and elucidate the underlying mechanisms. METHODS Mice were pretreated with myricitrin before liver I/R injury modeling. The mice were pretreated with either myricitrin or vehicle prior to liver ischemia. Some mice were further pretreated with the PI3K inhibitor LY294002. Liver tissues and blood samples were collected after 6 h of reperfusion. The degree of liver damage was determined by the serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and lactic dehydrogenase (LDH) and histological examinations. The tumour necrosis factor-α (TNF-α), interleukin--1β (IL-1β), IL-4 and IL-10 expression levels were assessed by qRT-PCR and enzyme-linked immunosorbent assays (ELISAs). Serum superoxide dismutase (SOD) activity, catalase (CAT) activity, and contents of malondialdehyde (MDA), glutathione (GSH) and nitric oxide (NO) contents were measured. Western blotting and caspase-3 activity were conducted to determine the effect of myricitrin on apoptosis. The expression levels of proliferation related genes (Cyclin D1 and Cyclin E1) were determined by qRT-PCR and western-blotting. The expression of p-Akt, p-mTOR and p-eNOS in liver tissue were investigated by western-blotting. RESULTS Myricitrin not only significantly decreased the ALT, AST and LDH levels but also reduced the necrotic areas in the liver tissue compared with liver I/R injury group. In addition, myricitrin pretreatment alleviated liver injury by inhibiting the inflammatory response and suppressing oxidative stress. Western blotting and caspase-3 activity revealed that myricitrin inhibited liver I/R induced-apoptosis. Myricitrin promoted hepatocyte proliferation following liver I/R injury by upregulating the expression levels of Cyclin D1 and Cyclin E1. Further experiments indicated that the myricitrin pretreatment increased nitric oxide (NO) production by activating the PI3K/Akt signaling pathway. However, myricitrin triggered the hepatocyte proliferation and NO synthase activation was blocked by LY294002. CONCLUSION These results demonstrate that myricitrin alleviates liver I/R injury by suppressing oxidative stress, the inflammatory response, and apoptosis, improving liver proliferation and upregulating p-eNOS expression.
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Affiliation(s)
- Yuntai Shen
- School of Clinical Medicine, Weifang Medical University, Weifang 266003, China
| | - Xiangrong Shen
- Department of Chinese Medicine, Zhucheng Shiqiaozi Hospital, Weifang 262208, China; Department of Chinese Medicine, The Affiliated Hospital of Qingdao University, Qingdao 260153, China
| | - Yao Cheng
- Department of Anesthesiology, Zhucheng People's Hospital, Weifang 262200, China
| | - Yulan Liu
- Department of Nursing, Zhucheng People's Hospital, Weifang 262200, China.
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25
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Zhang S, Feng Z, Gao W, Duan Y, Fan G, Geng X, Wu B, Li K, Liu K, Peng C. Aucubin Attenuates Liver Ischemia-Reperfusion Injury by Inhibiting the HMGB1/TLR-4/NF-κB Signaling Pathway, Oxidative Stress, and Apoptosis. Front Pharmacol 2020; 11:544124. [PMID: 33013386 PMCID: PMC7506056 DOI: 10.3389/fphar.2020.544124] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 08/24/2020] [Indexed: 12/16/2022] Open
Abstract
Liver ischemia-reperfusion injury (IRI) is a common clinical event with high morbidity in patients undergoing complex liver surgery or having abdominal trauma. Inflammatory and oxidative stress responses are the main contributing factors in liver IRI. The iridoid glucoside aucubin (AU) has good anti-inflammatory and antioxidative effects; however, there are no relevant reports on the protective effect of glucosides on hepatic IRI. The purpose of this study was to determine whether AU pretreatment could prevent liver IRI and to explore the mechanism. Sprague–Dawley rats were randomly divided into five groups. The sham operation and IRI control groups were given intraperitoneal injections of normal saline, while the AU low-dose (AU-L) group, AU medium-dose (AU-M) group, and AU high-dose (AU-H) group were given intraperitoneal injections of AU at doses of 1, 5, and 10 mg/kg/day, respectively. After 10 d, liver IRI (70% liver ischemia for 1 h, reperfusion for 6 h) was surgically established in all groups except the sham group. Our results confirmed that liver injury was significantly aggravated after hepatic ischemia-reperfusion. AU alleviated the increase of transaminase and pathological changes induced by ischemia-reperfusion and improved liver damage. AU could also ameliorate the inflammatory and oxidative stress responses induced by ischemia-reperfusion and reduced expression of high mobility group protein (HMG)B1, receptor for advanced glycation end-products (RAGE), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and reactive oxygen species (ROS). Moreover, AU reduced ischemia-reperfusion-induced mitochondrial dysfunction and cells apoptosis, increased peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and uncoupling (UCP)2 protein expression, and reduced caspase-3, cleaved caspase-3, and Cytochrome P450 proteins (CYP) expression. To determine expression levels of the Toll-like receptor (TLR)-4/nuclear factor-κB (NF-κB) pathway-related proteins in vitro and in vivo, we also measured TLR-4, myeloid differentiation factor88 (MyD88), NF-κB P65, p-P65, I-kappa-B-alpha (IκB-α), and p-IκB-α levels. The results showed that AU effectively inhibited activation of the TLR-4/NF-κB signaling pathway. In conclusion, we showed for the first time a hepatoprotective effect for AU in liver IRI, which acted by inhibiting the HMGB1/TLR-4/NF-κB signaling pathway, oxidative stress, and apoptosis. Pretreatment with AU may be a promising strategy for preventing liver IRI.
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Affiliation(s)
- Shilong Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Zanjie Feng
- Department of Biochemistry and Molecular Biology, Zunyi Medical University, Zunyi, China
| | - Weidong Gao
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yuling Duan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Guoxin Fan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Xin Geng
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Bo Wu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Kai Li
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Kangwei Liu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Cijun Peng
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
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Camerlo A, Magallon C, Vanbrugghe C, Chiche L, Gaudon C, Rinaldi Y, Fara R. Robotic hepatic parenchymal transection: a two-surgeon technique using ultrasonic dissection and irrigated bipolar coagulation. J Robot Surg 2020; 15:539-546. [PMID: 32779132 DOI: 10.1007/s11701-020-01138-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 08/03/2020] [Indexed: 02/06/2023]
Abstract
Liver transection is the most challenging part of hepatectomy due to the risk of hemorrhage which is associated with postoperative morbidity and mortality and reduced long-term survival. Parenchymal ultrasonic dissection (UD) with bipolar coagulation (BPC) has been widely recognized as a safe, effective, and standard technique during open and laparoscopic hepatectomy. We here introduce our technique of robotic liver transection using UD with BPC and report on short-term perioperative outcomes. From a single-institution prospective liver surgery database, we identified patients who underwent robotic liver resection. Demographic, anesthetic, perioperative, and oncologic data were analyzed. Fifty patients underwent robotic liver resection using UD and BPC for liver malignancies (n = 42) and benign lesions (n = 8). The median age of the patients was 67 years and 28 were male. According to the difficulty scoring system, 60% (n = 30) of liver resection were considered difficult. Three cases (6%) were converted to open surgery. The median operative time was 240 min, and the median estimated blood loss was 200 ml; 2 patients required operative transfusions. The overall complication rate was 38% (grade I, 29; grade II, 15; grade III, 3; grade IV, 1). Seven patients (14%) experienced biliary leakage. The median length of hospital stay post-surgery was 7 (range 3-20) days. The R0 resection rate was 92%. Robotic parenchymal transection using UD and irrigated BPC appears a simple, safe, and effective technique. However, our results must be confirmed in larger series or in randomized controlled trials.
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Affiliation(s)
- Antoine Camerlo
- Department of Digestive Surgery Hôpital Européen, 6 rue désirée Clary, 13003, Marseille, France.
| | - Cloé Magallon
- Department of Digestive Surgery Hôpital Européen, 6 rue désirée Clary, 13003, Marseille, France
| | - Charles Vanbrugghe
- Department of Digestive Surgery Hôpital Européen, 6 rue désirée Clary, 13003, Marseille, France
| | - Laurent Chiche
- Department of Clinical Research Hôpital Européen, 6 rue désirée Clary, 13003, Marseille, France
| | - Chloé Gaudon
- Department of Radiology Hôpital Européen, 6 rue désirée Clary, 13003, Marseille, France
| | - Yves Rinaldi
- Department of Digestive Surgery Hôpital Européen, 6 rue désirée Clary, 13003, Marseille, France
| | - Régis Fara
- Department of Digestive Surgery Hôpital Européen, 6 rue désirée Clary, 13003, Marseille, France
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Man Kim J, Hwang S, Lee KW, Lee JG, Ryu JH, Kim BW, Choi DL, You YK, Kim DS, Nah YW, Kang KJ, Cho JY, Hong G, Choi IS, Yu HC, Choi D, Kim MS, The Korean Organ Transplantation Registry Study Group. New-onset diabetes after adult liver transplantation in the Korean Organ Transplantation Registry (KOTRY) study. Hepatobiliary Surg Nutr 2020; 9:425-439. [PMID: 32832494 PMCID: PMC7423540 DOI: 10.21037/hbsn.2019.10.29] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 08/05/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) is a serious complication following liver transplantation (LT). The present study aimed to investigate the incidence of and risk factors for NODAT using the Korean Organ Transplantation Registry (KOTRY) database. METHODS Patients with history of pediatric transplantation (age ≤18 years), re-transplantation, multi-organ transplantation, or pre-existing diabetes mellitus were excluded. A total of 1,919 non-diabetic adult patients who underwent a primary LT between May 2014 and December 2017 were included. Risk factors were identified using Cox regression analysis. RESULTS NODAT occurred in 19.7% (n=377) of adult liver transplant recipients. Multivariate analysis showed steroid use, increased age, and high body mass index (BMI) in recipients, and implantation of a left-side liver graft was closely associated with NODAT in adult LT. In living donor liver transplant (LDLT) patients (n=1,473), open donor hepatectomy in the living donors, steroid use, small for size liver graft (graft to recipient weight ratio ≤0.8), increased age, and high BMI in the recipient were predictive factors for NODAT. The use of antimetabolite and basiliximab induction reduced the incidence of NODAT in adult LT and in adult LDLT. CONCLUSIONS Basiliximab induction, early steroid withdrawal, and antimetabolite therapy may prevent NODAT after adult LT. High BMI or advanced age in liver recipients, open donor hepatectomy in living donors, and small size liver graft can predict the occurrence of NODAT after adult LT or LDLT.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Jae-Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
| | - Dong-Sik Kim
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Koo Jeong Kang
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
| | - Geun Hong
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
| | - In Seok Choi
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
| | - Hee Chul Yu
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
| | - Dongho Choi
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - The Korean Organ Transplantation Registry Study Group
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
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Hasegawa Y, Nitta H, Takahara T, Katagiri H, Kanno S, Umemura A, Akiyama Y, Iwaya T, Otsuka K, Sasaki A. Glucocorticoid use and ischemia-reperfusion injury in laparoscopic liver resection: Randomized controlled trial. Ann Gastroenterol Surg 2020; 4:76-83. [PMID: 32021961 PMCID: PMC6992679 DOI: 10.1002/ags3.12298] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 10/19/2019] [Accepted: 10/27/2019] [Indexed: 12/19/2022] Open
Abstract
AIM Laparoscopic liver resection (LLR) is increasingly carried out worldwide. However, there are concerns regarding ischemia-reperfusion injury caused by pneumoperitoneum and the Pringle maneuver. It is not clear whether perioperative use of glucocorticoids lowers the risk of ischemia-reperfusion hepatic injury in LLR as has been reported for open liver resection. The aim of the present study was to investigate the role of perioperative glucocorticoid use in improving hepatic function and surgical outcomes after LLR. METHODS In this double-blind, randomized controlled trial (UMIN000013823), we enrolled 130 patients who presented to our institution for LLR between April 2014 and October 2018. Six patients were excluded, resulting in 124 patients being randomized to either the glucocorticoid or the control group. Preoperatively, patients in the glucocorticoid group received 500 mg methylprednisolone in saline solution, patients in the control group saline solution only. Surgical outcomes and blood parameters were compared between the two groups. RESULTS The Pringle maneuver could not be carried out in 24 patients, resulting in 50 patients in each group being included in the analysis. Postoperatively, total, direct and indirect bilirubin, and C-reactive protein and interleukin-6 levels were significantly lower, albumin levels were significantly higher, and prothrombin time was significantly shorter in the glucocorticoid than in the control group. Surgical outcomes were not significantly different between the groups. CONCLUSION This first report on preoperative glucocorticoid use in LLR showed that it significantly improved postoperative liver function and thus might enhance the safety of LLR.
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Affiliation(s)
- Yasushi Hasegawa
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
| | - Hiroyuki Nitta
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
| | - Takeshi Takahara
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
| | - Hirokatsu Katagiri
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
| | - Shoji Kanno
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
| | - Akira Umemura
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
| | - Yuji Akiyama
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
| | - Takeshi Iwaya
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
| | - Koki Otsuka
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
| | - Akira Sasaki
- Department of SurgeryIwate Medical University School of MedicineMorioka CityJapan
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Yang L, Zhang Z, Kong J, Wang W. Systematic Review and Meta-Analysis of the Benefit and Safety of Preoperative Administration of Steroid in Patients Undergoing Liver Resection. Front Pharmacol 2019; 10:1442. [PMID: 31849683 PMCID: PMC6894012 DOI: 10.3389/fphar.2019.01442] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 11/12/2019] [Indexed: 02/05/2023] Open
Abstract
Objective: To evaluate the benefit and safety of preoperative administration of steroid in patients undergoing liver resection. Methods: Randomized controlled trials (RCTs) which comparing preoperative administration of steroid in patients undergoing liver resection with control group were identified through a systematic literature search in PubMed, Embase, and Cochrane Library Central databases. This meta-analysis was carried out to assess the liver function, inflammatory response, and postoperative complications after liver surgery. Results: Six RCTs including 411 patients were reviewed. The pooled result showed that there was no significant difference in the incidence of overall complications between the steroid group and the control group (OR, 0.57; 95% CI, 0.27–1.17; P = 0.13). With respect to specific complications, no significant difference was detected between the two groups in infection complications (OR, 0.95; 95% CI, 0.13–6.95; P = 0.96), wound complications (OR, 0.65; 95% CI, 0.32–1.33; P = 0.24), liver failure (OR, 0.41; 95% CI, 0.10–1.64; P = 0.21), bile leakage (OR, 0.57; 95% CI, 0.17–1.89; P = 0.36), and pleural effusion (OR, 1.24; 95% CI, 0.55–2.78; P = 0.60). For liver function, the level of serum total bilirubin (TB) on postoperative day 1 (POD 1) was significantly decreased associated with the intervention of steroid (MD, −0.54; 95% CI, −0.94 to −0.15; P = 0.007). However, no significant difference was found in the level of alanine aminotransferase (ALT) (MD, −69.39; 95% CI, −226.52 to 87.75; P = 0.39) and aspartate aminotransferase (AST) (MD, −93.44; 95% CI, −275.68 to 88.80; P = 0.31) on POD 1 between the two groups. Serum IL-6 level on POD 1 (MD, −57.98; 95% CI, −73.04 to −42.91; P < 0.00001) and CRP level on POD 3 (MD, −4.83; 95% CI, −6.07 to −3.59; P < 0.00001) were significantly reduced in the steroid group comparing to the control group. Compared with the control group, the level of early postoperative IL-10 was significant higher in the steroid group (MD, 17.89; 95% CI, 3.89 to 31.89; P = 0.01). Conclusion: Preoperative administration of steroid in liver resection can promote the recovery of liver function and inhibit the inflammatory response without increasing postoperative complications. Further studies should focus on determining which patients would benefit most from the steroid.
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Affiliation(s)
- Lingpeng Yang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Zifei Zhang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China.,Department of General Surgery, The Affiliated Hospital of Xizang Minzu University, Xianyang, China
| | - Junjie Kong
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Wentao Wang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
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Jia LH, Ma XM, Yan QL, Wu XS, Chen Y, Ye QH, Wang ZJ, Qiu MM, Zhu JH. Autologous Blood Transfusion and Pringle Maneuver in Laparoscopic Segmental Hepatectomy for Benign Hepatic Neoplasms: A Retrospective Study. J Laparoendosc Adv Surg Tech A 2019; 29:1571-1576. [PMID: 31682205 DOI: 10.1089/lap.2019.0407] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objectives: To investigate the effect of autologous blood transfusion (ABT) and Pringle maneuver (PM) on postoperative early liver function and short-term postoperative results following laparoscopic liver resection in patients with benign hepatic neoplasms. Materials and Methods: We retrospectively analyzed the clinical data for 125 consecutive patients who underwent laparoscopic segmental hepatectomy from January 2015 to May 2018 (68 in the ABT group versus 57 in the PM group). We compared patients' characteristics and intra- and postoperative short-term outcomes between the groups. Results: The 2 groups were well matched regarding patients' clinical characteristics, types of liver resection, operative time, and histopathological findings (P > .05). Median blood loss was significantly lower in the PM group versus the ABT group (200 mL versus 750 mL, respectively; P < .01), and overall complication rates were similar (n = 12 [17%] versus n = 9 [16%], respectively; P > .05). The ABT group had significantly lower mean levels of total bilirubin, indirect bilirubin, aspartate transaminase, and alanine aminotransferase on postoperative days 1 and 3 (P < .05). The ABT group had a shorter hospital stay compared with the PM group (5.8 days versus 7.7 days, respectively; P < .05) and lower hospitalization costs (55,400 ± 15,400 versus 667,000 ± 21,600 CN dollars, respectively; P < .05). Conclusions: Compared with Pringle's maneuver, laparoscopic hepatectomy with ABT promoted early recovery of liver function and reduced hospitalization costs in select patients with benign hepatic neoplasms.
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Affiliation(s)
- Li-Hua Jia
- Department of General Surgery, Jinhua Hospital of TCM, Jinhua, China
| | - Xiao-Ming Ma
- Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Qiu-Liang Yan
- Department of General Surgery, Jinhua People's Hospital, Jinhua, China
| | - Xiang-Song Wu
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Chen
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qing-Huang Ye
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhi-Jiang Wang
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Man-Man Qiu
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jin-Hui Zhu
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Sevoflurane relieves hepatic ischemia-reperfusion injury by inhibiting the expression of Grp78. Biosci Rep 2018; 38:BSR20180549. [PMID: 30217942 PMCID: PMC6172422 DOI: 10.1042/bsr20180549] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 08/07/2018] [Accepted: 09/03/2018] [Indexed: 12/30/2022] Open
Abstract
Purpose: This article aimed to study the role of sevoflurane pre-conditioning in hepatic ischemia–reperfusion and its potential mechanism. Methods: Rat liver ischemia–reperfusion model was constructed. Serum TNF-α, IL-1β, IL-10, and IL-6 concentrations were detected by ELISA. Malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in liver homogenate were determined. Hematoxylin–Eosin (HE) staining, Tunel, and immunohistochemistry were performed. Ischemia–reperfusion hepatocyte model was established. Cells transfection was conducted. Apoptosis was observed by flow cytometry. Quantitative real-time PCR (qRT-PCR) and Western blotting analysis were used. Results: Compared with I/R group, liver damage degree, liver cell apoptosis, and glucose regulatory protein 78 (Grp78) expression was obviously reduced in rats of SEV group. TNF-α, IL-1β, and IL-6 concentrations were also significantly increased (P<0.01). MDA and NO concentrations were dramatically lower (P<0.01) and SOD concentration was significantly higher (P<0.01). Apoptosis rate, Grp78, PERK, eIF2α, and p-c-JNK/JNK expression was also significantly decreased (P<0.01). Sevoflurane significantly reduced apoptosis and expression of PERK, eIF2α, p-c-JNK/JNK by inhibiting the expression of Grp78 (P<0.01). Conclusion: Sevoflurane relieves hepatic ischemia–reperfusion injury by inhibiting the expression of Grp78.
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Garnier J, Faucher M, Marchese U, Meillat H, Mokart D, Ewald J, Delpero JR, Turrini O. Severe acute kidney injury following major liver resection without portal clamping: incidence, risk factors, and impact on short-term outcomes. HPB (Oxford) 2018; 20:865-871. [PMID: 29691124 DOI: 10.1016/j.hpb.2018.03.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 02/20/2018] [Accepted: 03/30/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Acute kidney injury (AKI) following major hepatectomy (MH) remains inadequately investigated. This retrospective study aimed to assess the risk factors and prognostic value of AKI on short-term outcomes following MH without portal pedicle clamping. METHODS From January 2014 through June 2017, 111 consecutive patients underwent MH without portal pedicle clamping, but with intraoperative low-crystalloid infusion. Kidney Disease Improving Global Outcomes stages II and III were classified as severe AKI. RESULTS A total of 102 patients did not develop AKI or only AKI stage I (92%, control group), whereas 9 patients developed severe AKI (8%, severe AKI group). Hepatectomy (P = 0.002) and surgery (P = 0.011) durations were longer in the severe AKI group. Clavien-Dindo grades 3 to 5 morbidity (55% versus 9%, P = 0.001), liver failure (P = 0.017), and 90-day mortality (33% versus 2%, P = 0.003) were significantly higher in the severe AKI group. After a multivariate analysis, the duration of hepatectomy (cut-off: 250 min; P = 0.029) and urea serum levels on postoperative day 3 (P = 0.006) were identified as independent predictors of severe AKI. DISCUSSION Severe AKI, is common with increased duration of hepatectomy, was associated with poor short-term outcomes, and can be predicted by operative duration greater than 250 minutes.
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Affiliation(s)
- Jonathan Garnier
- Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France; AixMarseille University, Marseille, France.
| | - Marion Faucher
- Department of Anesthesiology and Critical Care, Institut Paoli Calmettes, Marseille, France
| | - Ugo Marchese
- Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France; AixMarseille University, Marseille, France
| | - Hélène Meillat
- Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France
| | - Djamel Mokart
- Department of Anesthesiology and Critical Care, Institut Paoli Calmettes, Marseille, France
| | - Jacques Ewald
- Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France
| | - Jean-Robert Delpero
- Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France; AixMarseille University, Marseille, France
| | - Olivier Turrini
- Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France; AixMarseille University, Marseille, France
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Martino EA, Baiardo Redaelli M, Sardo S, Lembo R, Giordano VF, Winterton D, Ruggeri L, Hajjar LA, Zangrillo A, Landoni G. Steroids and Survival in Critically Ill Adult Patients: A Meta-analysis of 135 Randomized Trials. J Cardiothorac Vasc Anesth 2018; 32:2252-2260. [PMID: 29793761 DOI: 10.1053/j.jvca.2018.04.017] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Corticosteroids have important effects on intermediate outcomes in critically ill patients, but their effect on survival is unknown. The objective of this meta-analysis was to analyze the effect on mortality of corticosteroids in critical and perioperative settings. DESIGN A meta-analysis of randomized trials. SETTING PubMed, Embase, BioMed Central, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched to February 1, 2018, for randomized trials comparing corticosteroids with placebo or standard care. PARTICIPANTS Critically ill or surgical adult patients. INTERVENTIONS Corticosteroids compared with placebo or standard care. MEASUREMENTS AND MAIN RESULTS A total of 44,553 patients from 135 studies were included. Overall, mortality in the corticosteroid group and in the control group were similar (16% v 16%; p = 0.9). Subanalyses identified a beneficial effect of corticosteroids on survival in patients with respiratory system diseases (9% v 13%; p < 0.001) and bacterial meningitis (28% v 32%; p= 0.04), and a detrimental effect on survival in patients with traumatic brain injury (22% v 19%; p < 0.001). No differences in mortality were found in patients with cardiac diseases (7% v 6%; p = 0.7), in patients undergoing cardiac surgery (2.8% v 3.2% p = 0.14), and when treatment duration or patient age were considered. CONCLUSIONS This meta-analysis documents the safety of corticosteroids in the overall critically ill population with the notable exception of brain injury patients, a setting where the authors confirmed their detrimental effect on survival. A possible beneficial effect of corticosteroids on survival was found among patients with respiratory diseases and in patients with bacterial meningitis.
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Affiliation(s)
- Enrico A Martino
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Martina Baiardo Redaelli
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Salvatore Sardo
- Department of Medical Sciences "M. Aresu," University of Cagliari, Cagliari, Italy
| | - Rosalba Lembo
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Vito F Giordano
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Dario Winterton
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Laura Ruggeri
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Ludhmilla A Hajjar
- Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil
| | - Alberto Zangrillo
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
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Kemp R, Mole J, Gomez D. Current evidence for the use of N-acetylcysteine following liver resection. ANZ J Surg 2017; 88:E486-E490. [PMID: 29132195 DOI: 10.1111/ans.14295] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 10/10/2017] [Accepted: 10/11/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND N-acetylcysteine (NAC) has many uses in medicine; notable in the management of paracetamol toxicity, acute liver failure and liver surgery. The aim of this review was to critically appraise the published literature for the routine use of NAC in liver resection surgery. METHODS An electronic search was performed of EBSCOhost (Medline and CINAHL database), PubMed and the Cochrane Library for the period 1990-2016. MeSH headings: 'acetyl-cysteine', 'liver resection' and 'hepatectomy' were used to identify all relevant articles published in English. RESULTS Following the search criteria used, three articles were included. Two of these studies were randomized controlled trials. All the studies collated data on morbidity and mortality. All three studies did not show a significant difference in overall complications rates in patients that underwent hepatic resection that had NAC infusion compared with patients that did not. In one study, NAC administration was associated with a higher frequency of grade A post-hepatectomy liver failure. In another study, a significantly higher incidence of delirium was observed in the NAC group, which led to the trial to be terminated early. CONCLUSION The current published data do not support the routine use of NAC following liver resection.
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Affiliation(s)
- Richard Kemp
- Department of Anaesthesia, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Jonathan Mole
- Department of Anaesthesia, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Dhanny Gomez
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.,NIHR Nottingham Digestive Disease Biomedical Research Unit, University of Nottingham, Nottingham, UK
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Scientific surgery. Br J Surg 2017. [DOI: 10.1002/bjs.10491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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