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Han C, Wu Y, Rong J, Xia Q, Du D. Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species. Antioxidants (Basel) 2025; 14:95. [PMID: 39857429 PMCID: PMC11759826 DOI: 10.3390/antiox14010095] [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: 10/22/2024] [Revised: 12/29/2024] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
Acute pancreatitis (AP) is a potentially fatal acute digestive disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that catalyzes hypoxanthine and xanthine to produce urate and is accompanied by the generation of reactive oxygen species (ROS) in purine catabolism. Considerable preclinical and clinical studies have been conducted over many decades to investigate the role of XO in the pathogenesis of AP and its potential targeting therapeutic value. There is no doubt that the ROS generated by irreversibly activated XO participates in the local pancreas and multiple organ failure during AP. However, the optimal timing and doses for therapeutic interventions targeting XO in animal studies and the clinic, as well as the additional molecular mechanisms through which XO contributes to disease onset and progression, including metabolic regulation, remain to be elucidated. This review summarized the benefits and contradictions of using XO inhibitors in animal models, offered mechanisms other than ROS, and discussed the difficulties faced in clinical trials. We hope to provide a perspective on the future worthwhile basic and clinical research on XO by analyzing its chemical and biological characteristics, as well as the progress of its regulatory mechanisms in AP.
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Affiliation(s)
- Chenxia Han
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yaling Wu
- Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Juan Rong
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, Chengdu 610031, China
| | - Qing Xia
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Dan Du
- Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
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Rong J, Han C, Huang Y, Wang Y, Qiu Q, Wang M, Wang S, Wang R, Yang J, Li X, Hu C, Chen Z, Deng L, Huang W, Xia Q, Du D. Inhibition of xanthine oxidase alleviated pancreatic necrosis via HIF-1 α-regulated LDHA and NLRP3 signaling pathway in acute pancreatitis. Acta Pharm Sin B 2024; 14:3591-3604. [PMID: 39220867 PMCID: PMC11365396 DOI: 10.1016/j.apsb.2024.04.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 02/06/2024] [Accepted: 03/15/2024] [Indexed: 09/04/2024] Open
Abstract
Acute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1α)-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13C6-glucose to 13C3-lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.
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Affiliation(s)
- Juan Rong
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Chenxia Han
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Yan Huang
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Yiqin Wang
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Qi Qiu
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Manjiangcuo Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China
| | - Shisheng Wang
- Proteomics-Metabolomics Platform, Research Core Facility, Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu 610093, China
| | - Rui Wang
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China
| | - Juqin Yang
- Biobank, West China Hospital, Sichuan University, Chengdu 610093, China
| | - Xia Li
- West China School of Nursing, Sichuan University, Chengdu 610041, China
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chenggong Hu
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zhiyao Chen
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Lihui Deng
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Wei Huang
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
- Biobank, West China Hospital, Sichuan University, Chengdu 610093, China
| | - Qing Xia
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Dan Du
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China
- Proteomics-Metabolomics Platform, Research Core Facility, Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu 610093, China
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3
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Rojas-Victoria EJ, Hernández-Ruiz SI, García-Perdomo HA. Effectiveness of the pharmacological therapy to prevent post ERCP acute pancreatitis: a network meta-analysis. Expert Rev Gastroenterol Hepatol 2024; 18:203-215. [PMID: 38725175 DOI: 10.1080/17474124.2024.2345640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 04/17/2024] [Indexed: 05/24/2024]
Abstract
OBJECTIVE To determine the effectiveness of the different pharmacological agents in preventing post-ERCP acute pancreatitis. METHODS We included clinical trials of pharmacological interventions for prophylaxis of acute post-ERCP pancreatitis. The event evaluated was acute pancreatitis. We conducted a search strategy in MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials from inception to nowadays. We reported the information in terms of relative risks (RR) with a 95% confidence interval. We assessed the heterogeneity using the I2 test. RESULTS We included 84 studies for analysis (30,463 patients). The mean age was 59.3 years (SD ± 7.01). Heterogeneity between studies was low (I2 = 34.4%) with no inconsistencies (p = 0.2567). Post ERCP pancreatitis was less in prophylaxis with NSAIDs (RR 0.65 95% CI [0.52 to 0.80]), aggressive hydration with Lactate Ringer (RR 0.32 95% CI [0.12-0.86]), NSAIDs + isosorbide dinitrate (RR 0.28 95% CI [0.11-0.71]) and somatostatin and analogues (RR 0.54 [0.43 to 0.68]) compared with placebo. CONCLUSIONS NSAIDs, the Combination of NSAIDs + isosorbide dinitrate, somatostatin and analogues, and aggressive hydration with lactate ringer are pharmacological strategies that can prevent post-ERCP pancreatitis when compared to placebo. More clinical trials are required to determine the effectiveness of these drugs.
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Affiliation(s)
| | | | - Herney Andrés García-Perdomo
- Division of Urology/Urooncology, Department of Surgery, School of Medicine, Universidad del Valle, Cali, Colombia
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Zhang J, Ge P, Liu J, Luo Y, Guo H, Zhang G, Xu C, Chen H. Glucocorticoid Treatment in Acute Respiratory Distress Syndrome: An Overview on Mechanistic Insights and Clinical Benefit. Int J Mol Sci 2023; 24:12138. [PMID: 37569514 PMCID: PMC10418884 DOI: 10.3390/ijms241512138] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/20/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), triggered by various pathogenic factors inside and outside the lungs, leads to diffuse lung injury and can result in respiratory failure and death, which are typical clinical critical emergencies. Severe acute pancreatitis (SAP), which has a poor clinical prognosis, is one of the most common diseases that induces ARDS. When SAP causes the body to produce a storm of inflammatory factors and even causes sepsis, clinicians will face a two-way choice between anti-inflammatory and anti-infection objectives while considering the damaged intestinal barrier and respiratory failure, which undoubtedly increases the difficulty of the diagnosis and treatment of SAP-ALI/ARDS. For a long time, many studies have been devoted to applying glucocorticoids (GCs) to control the inflammatory response and prevent and treat sepsis and ALI/ARDS. However, the specific mechanism is not precise, the clinical efficacy is uneven, and the corresponding side effects are endless. This review discusses the mechanism of action, current clinical application status, effectiveness assessment, and side effects of GCs in the treatment of ALI/ARDS (especially the subtype caused by SAP).
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Affiliation(s)
- Jinquan Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
| | - Peng Ge
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Jie Liu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Haoya Guo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Guixin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Caiming Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Comprehensive Cancer Center, Monrovia, CA 91016, USA
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
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5
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Akshintala VS, Kanthasamy K, Bhullar FA, Sperna Weiland CJ, Kamal A, Kochar B, Gurakar M, Ngamruengphong S, Kumbhari V, Brewer-Gutierrez OI, Kalloo AN, Khashab MA, van Geenen EJM, Singh VK. Incidence, severity, and mortality of post-ERCP pancreatitis: an updated systematic review and meta-analysis of 145 randomized controlled trials. Gastrointest Endosc 2023; 98:1-6.e12. [PMID: 37004815 DOI: 10.1016/j.gie.2023.03.023] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 03/01/2023] [Accepted: 03/21/2023] [Indexed: 04/04/2023]
Abstract
BACKGROUND AND AIMS The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs). METHODS The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality. RESULTS One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48). CONCLUSIONS The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon.
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Affiliation(s)
- Venkata S Akshintala
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Kavin Kanthasamy
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Furqan A Bhullar
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | | | - Ayesha Kamal
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Bharati Kochar
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Merve Gurakar
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | | | - Vivek Kumbhari
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | | | - Anthony N Kalloo
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Mouen A Khashab
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Erwin-Jan M van Geenen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Vikesh K Singh
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
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6
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Borrelli de Andreis F, Mascagni P, Schepis T, Attili F, Tringali A, Costamagna G, Boškoski I. Prevention of post-ERCP pancreatitis: current strategies and novel perspectives. Therap Adv Gastroenterol 2023; 16:17562848231155984. [PMID: 36895283 PMCID: PMC9989421 DOI: 10.1177/17562848231155984] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 01/23/2023] [Indexed: 03/08/2023] Open
Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure that might lead to severe adverse events. Post-ERCP pancreatitis (PEP) is the most common post-procedural complication, which is related to significant mortality and increasing healthcare costs. Up to now, the prevalent approach to prevent PEP consisted of employing pharmacological and technical expedients that have been shown to improve post-ERCP outcomes, such as the administration of rectal nonsteroidal anti-inflammatory drugs, aggressive intravenous hydration, and the placement of a pancreatic stent. However, it has been reported that PEP originates from a more complex interaction of procedural and patient-related factors. Appropriate ERCP training has a pivotal role in PEP prevention strategy, and it is not a chance that a low PEP rate is universally considered one of the most relevant indicators of proficiency in ERCP. Scant data on the acquisition of skills during the ERCP training are currently available, although some efforts have been recently done to shorten the learning curve by way of simulation-based training and demonstrate competency by meeting technical requirements as well as adopting skill evaluation scales. Besides, the identification of adequate indications for ERCP and accurate pre-procedural risk stratification of patients might help to reduce PEP occurrence regardless of the endoscopist's technical abilities, and generally preserve safety in ERCP. This review aims at delineating current preventive strategies and highlighting novel perspectives for a safer ERCP focusing on the prevention of PEP.
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Affiliation(s)
- Federica Borrelli de Andreis
- First Department of Internal Medicine, Fondazione IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy
- Gastroenterology Unit, Istituti Clinici Maugeri, University of Pavia, Pavia, Italy
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Pietro Mascagni
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Institute of Image-Guided Surgery, IHU-Strasbourg, France
| | - Tommaso Schepis
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Fabia Attili
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Andrea Tringali
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Guido Costamagna
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica Del Sacro Cuore di Roma, Roma, Italy
| | - Ivo Boškoski
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, Rome, 00168, Italy
- IHU Strasbourg 1, Place de l’Hopital 67091 Strasbourg Cedex, France
- Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica Del Sacro Cuore di Roma, Roma, Italy
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7
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Patel A, Zhang M, Liao G, Karkache W, Montroy J, Fergusson DA, Khadaroo RG, Tran DTT, McIsaac DI, Lalu MM. A Systematic Review and Meta-Analysis Examining the Impact of Age on Perioperative Inflammatory Biomarkers. Anesth Analg 2021; 134:751-764. [PMID: 34962902 DOI: 10.1213/ane.0000000000005832] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Dysregulation of immune responses to surgical stress in older patients and those with frailty may manifest as differences in inflammatory biomarkers. We conducted a systematic review and meta-analysis to examine differences in perioperative inflammatory biomarkers between older and younger patients, and between patients with and without frailty. METHODS MEDLINE, Embase, Cochrane, and CINAHL databases were searched (Inception to June 23, 2020). Observational or experimental studies reporting the perioperative level or activity of biomarkers in surgical patients stratified by age or frailty status were included. The primary outcome was inflammatory biomarkers (grouped by window of ascertainment: pre-op; post-op: <12 hours, 12-24 hours, 1-3 days, 3 days to 1 week, and >1 week). Quality assessment was conducted using the Newcastle-Ottawa Scale. Inverse-variance, random-effects meta-analysis was conducted. RESULTS Forty-five studies (4263 patients) were included in the review, of which 36 were pooled for meta-analysis (28 noncardiac and 8 cardiac studies). Two studies investigated frailty as the exposure, while the remaining investigated age. In noncardiac studies, older patients had higher preoperative levels of interleukin (IL)-6 and C-reactive protein (CRP), lower preoperative levels of lymphocytes, and higher postoperative levels of IL-6 (<12 hours) and CRP (12-24 hours) than younger patients. In cardiac studies, older patients had higher preoperative levels of IL-6 and CRP and higher postoperative levels of IL-6 (<12 hours and >1 week). CONCLUSIONS Our findings demonstrate a paucity of frailty-specific studies; however, the presence of age-associated differences in the perioperative inflammatory response is consistent with age-associated states of chronic systemic inflammation and immunosenescence. Additional studies assessing frailty-specific changes in the systemic biologic response to surgery may inform the development of targeted interventions.
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Affiliation(s)
- Abhilasha Patel
- From the Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - MengQi Zhang
- From the Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Gary Liao
- From the Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Wassim Karkache
- From the Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | | | - Dean A Fergusson
- From the Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.,Clinical Epidemiology Program.,Blueprint Translational Group, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Rachel G Khadaroo
- Department of Surgery and Critical Care Medicine, University of Alberta, Walter C Mackenzie Health Sciences Centre, Edmonton, Alberta, Canada
| | - Diem T T Tran
- Clinical Epidemiology Program.,Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Daniel I McIsaac
- Clinical Epidemiology Program.,Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Manoj M Lalu
- Clinical Epidemiology Program.,Blueprint Translational Group, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.,Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
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8
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Honselmann KC, Antoine C, Frohneberg L, Deichmann S, Bolm L, Braun R, Lapshyn H, Petrova E, Keck T, Wellner U, Bausch D. A simple nomogram for early postoperative risk prediction of clinically relevant pancreatic fistula after pancreatoduodenectomy. Langenbecks Arch Surg 2021; 406:2343-2355. [PMID: 34009458 PMCID: PMC8578094 DOI: 10.1007/s00423-021-02184-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 04/28/2021] [Indexed: 01/08/2023]
Abstract
PURPOSE Postoperative pancreatic fistulae (POPF) present a serious and life-threatening complication after pancreatic head resections (PD). Therefore, reliable risk stratification to identify those at risk is urgently needed. The aim of this study was to identify postoperative laboratory parameters for the prediction of POPF in the early postoperative period. METHODS One hundred eighty-two patients who underwent PD from 2012 until 2017 were retrospectively analyzed. Multivariate logistic regression was performed using the GLM (general linear model) method for model building. Two nomograms were created based on the GLM models of postoperative day one and postoperative day one to five. A cohort of 48 patients operated between 2018 and 2019 served as internal validation. RESULTS Clinically relevant pancreatic fistulae (CR-POPF) were present in 16% (n = 29) of patients. Patients with CR-POPF experienced significantly more insufficiencies of gastroenterostomies, delayed gastric emptying, and more extraluminal bleeding than patients without CR-POPF. Multivariate analysis revealed multiple postoperative predictive models, the best one including ASA, main pancreatic duct diameter, operation time, and serum lipase as well as leucocytes on day one. This model was able to predict CR-POPF with an accuracy of 90% and an AUC of 0.903. Two nomograms were created for easier use. CONCLUSION Clinically relevant fistula can be predicted using simple laboratory and clinical parameters. Not serum amylase, but serum lipase is an independent predictor of CR-POPF. Our simple nomograms may help in the identification of patients for early postoperative interventions.
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Affiliation(s)
- K C Honselmann
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - C Antoine
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - L Frohneberg
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - S Deichmann
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - L Bolm
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - R Braun
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - H Lapshyn
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - E Petrova
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - T Keck
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - U Wellner
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - D Bausch
- Department of Surgery, University Cancer Center, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany. .,Department of Surgery, Marien Hospital Herne-University Medical Center of the Ruhr-Universität Bochum, Hölkeskampring 40, 44625, Herne, Germany.
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9
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Lyu Y, Wang B, Cheng Y, Xu Y, Du W. Comparative Efficacy of 9 Major Drugs for Postendoscopic Retrograde Cholangiopancreatography Pancreatitis: A Network Meta-Analysis. Surg Laparosc Endosc Percutan Tech 2019; 29:426-432. [PMID: 31490455 DOI: 10.1097/sle.0000000000000707] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most common complications after ERCP. The optimal drugs for reducing the risk of PEP are still unclear. This study aimed to compare the efficacy of 9 major drugs used worldwide for the prevention of PEP through a network meta-analysis. METHODS We conducted a systematic search of the literature up to October 2018 on PubMed, Embase, Web of Science, the Cochrane Central Library, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing allopurinol, diclofenac, gabexate (GAB), glyceryl trinitrate (GTN), indomethacin, nafamostat, octreotide, somatostatin, and ulinastatin for protection against PEP were included. RESULTS Eighty-six randomized controlled trials involving 25,246 patients were included in this network meta-analysis. Results indicated that diclofenac, GAB, GTN, indomethacin, somatostatin, and ulinastatin were more effective than placebo with odds ratios ranging between 0.48 (95% credible interval, 0.26-0.86) for GAB and 0.61 (0.39-0.94) for somatostatin. However, allopurinol, nafamostat, and octreotide showed similar efficacy as placebo in reducing the risk of PEP. No significant differences were found in the efficacy between diclofenac, GAB, GTN, indomethacin, somatostatin, and ulinastatin. In terms of prognosis, GAB may be the most effective treatment (surface under the cumulative ranking curve=70.6%) and the least effective was octreotide (surface under the cumulative ranking curve=28%). CONCLUSIONS Although our analysis suggests that GAB may be the most effective drug in preventing PEP, the limitations of our study warrants more high-quality head-to-head trials of these clinical drugs in the future.
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Affiliation(s)
- Yunxiao Lyu
- Department of Hepatobiliary Surgery, Dongyang People's Hospital, Dongyang, Zhejiang, China
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10
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Perdigoto DN, Gomes D, Almeida N, Mendes S, Alves AR, Camacho E, Tomé L. Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in the Indomethacin Era - A Prospective Study. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2019; 26:176-183. [PMID: 31192286 DOI: 10.1159/000492313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Revised: 07/23/2018] [Indexed: 12/18/2022]
Abstract
Background and Aims Although endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure used to treat conditions affecting the biliopancreatic system, it can lead to several complications. Post-ERCP pancreatitis (PEP) is the most frequent one, with an incidence ranging from 3 to 14%. Our aim was to assess the potential risk factors associated with PEP occurrence in patients undergoing ERCP with indomethacin prophylaxis. Methods Prospective, single-center, real-world observational study (January to December 2015) with inclusion of patients submitted to ERCP, where relevant patient-related and procedure-related data had been collected. Patients had to have been admitted for a minimum of 24 h in order to establish the presence of early complications. All patients were submitted to PEP prophylaxis with 1 or 2 methods: rectal indomethacin and pancreatic duct (PD) stenting. Results A total of 188 patients who had undergone ERCP were included (52.7% women; mean age 69.2 ± 16.0 years) and PEP was diagnosed in 13 (6.9%). PEP prophylaxis consisted of indomethacin in all cases (100%) and PD stenting in 7.4%. The pancreatitis was mild in 11 patients (84.6%) and severe in the other 2. One of them died (0.5%). None of the patient-related risk factors were associated with changes in PEP probability. Of all patients, 33.0% had 2 or more procedure-related risk factors. A higher number of synchronous procedure-related risk factors showed a statistically significant correlation with PEP occurrence, p = 0.040. Conclusions The 6.9% PEP rate is considered acceptable since 33.0% patients had a medium-high risk for PEP due to challenging biliary cannulation. The total number of procedure-related risk factors seems to play a critical role in the development of PEP despite indomethacin prophylaxis.
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Affiliation(s)
- David N Perdigoto
- Gastroenterology Department, Coimbra Hospital and University Center, Coimbra, Portugal.,Medical School, Coimbra University, Coimbra, Portugal
| | - Dário Gomes
- Gastroenterology Department, Coimbra Hospital and University Center, Coimbra, Portugal.,Medical School, Coimbra University, Coimbra, Portugal
| | - Nuno Almeida
- Gastroenterology Department, Coimbra Hospital and University Center, Coimbra, Portugal.,Medical School, Coimbra University, Coimbra, Portugal
| | - Sofia Mendes
- Gastroenterology Department, Coimbra Hospital and University Center, Coimbra, Portugal
| | - Ana Rita Alves
- Gastroenterology Department, Coimbra Hospital and University Center, Coimbra, Portugal
| | - Ernestina Camacho
- Gastroenterology Department, Coimbra Hospital and University Center, Coimbra, Portugal
| | - Luís Tomé
- Gastroenterology Department, Coimbra Hospital and University Center, Coimbra, Portugal.,Medical School, Coimbra University, Coimbra, Portugal
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11
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Plavsic I, Žitinić I, Mikolasevic I, Poropat G, Hauser G. Endoscopic retrograde cholangiopancreatography-induced and non-endoscopic retrograde cholangiopancreatography-induced acute pancreatitis: Two distinct clinical and immunological entities? World J Gastrointest Endosc 2018; 10:259-266. [PMID: 30364685 PMCID: PMC6198307 DOI: 10.4253/wjge.v10.i10.259] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Revised: 06/10/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis (AP) is common gastrointestinal disease of varied aetiology. The most common cause of AP is gallstones, followed by alcohol abuse as an independent risk factor. With the increased need for invasive techniques to treat pancreatic and bile duct pathologies such as endoscopic retrograde cholangiopancreatography (ERCP), AP has emerged as the most frequent complication. While severe AP following ERCP is rare (0.5%), if it does develop it has a greater severity index compared to non-ERCP AP. Development of a mild form of AP after ERCP is not considered a clinically relevant condition. Differences in the clinical presentation and prognosis of the mild and severe forms have been found between non-ERCP AP and post-endoscopic pancreatitis (PEP). It has been proposed that AP and PEP may also have different immunological responses to the initial injury. In this review, we summarise the literature on clinical and inflammatory processes in PEP vs non-ERCP AP.
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Affiliation(s)
- Ivana Plavsic
- Department of Anesthesiology and Critical care medicine, Clinical Hospital Centre, Medical Faculty, University of Rijeka, Rijeka 51000, Croatia
| | - Ivana Žitinić
- Department of Emergency Medicine, Clinical Hospital Centre, Rijeka 51000, Croatia
| | - Ivana Mikolasevic
- Department of Internal Medicine, Division of Gastroenterology, Clinical Hospital Centre, Medical Faculty, University of Rijeka, Rijeka 51000, Croatia
| | - Goran Poropat
- Department of Internal Medicine, Division of Gastroenterology, Clinical Hospital Centre, Medical Faculty, University of Rijeka, Rijeka 51000, Croatia
| | - Goran Hauser
- Department of Internal Medicine, Division of Gastroenterology, Clinical Hospital Centre, Medical Faculty, Faculty of health Studies, University of Rijeka, Rijeka 51000, Croatia
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12
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Lyu Y, Cheng Y, Wang B, Xu Y, Du W. What is impact of nonsteroidal anti-inflammatory drugs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials. BMC Gastroenterol 2018; 18:106. [PMID: 29973142 PMCID: PMC6032784 DOI: 10.1186/s12876-018-0837-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 06/26/2018] [Indexed: 12/16/2022] Open
Abstract
Background Recently, although studies have investigated the role of NSAIDs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), selection of the ideal drug, the time and route of its administration for the appropriate population remain controversial. Methods A systematic search was done in sources including PubMed, Embase, Web of Science, the Cochrane Library Central, and ClinicalTrials.gov from from August 1, 1990 to August 1, 2017. Randomized controlled trials comparing the prophylactic use of NSAIDs versus a placebo were included. Statistical analysis was performed using the RevMan 5.3 software to assess the outcomes. Results A total of 21 randomized controlled trials were included in the meta-analysis. Our study showed that NSAIDs significantly reduced the incidence of PEP (RR, 0.61, 95%CI,0.52–0.72; p < 0.00001). The analysis showed that indomethacin administration post-ERCP (RR, 0.47; 95% CI, 0.31–0.70; p = 0.0002) appeared to be more effective in preventing PEP than indomethacin administration pre-ERCP (RR, 0.59; 95% CI, 0.45–0.79; P = 0.0003), but there was no significant difference between the high-risk and average-risk population(p = 0.13). In the diclofenac group, it was noted that administration of diclofenac pre-ERCP (RR, 0.32; 95% CI, 0.16–0.63; p = 0.001) was more effective than that in post-ERCP (RR, 0.65; 95% CI, 0.27–1.599; p = 0.35). The relative risk of PEP was 0.63 (95% CI, 0.27–1.50; p = 0.30) in high-risk patients and 0.41 (95% CI, 0.17–0.98; p = 0.02) in average-risk patients. With regard to the route of administration, PEP decreased significantly only in patients receiving the drug rectally (RR, 0.53; 95% CI, 0.44–0.63; p < 0.00001), but not for those who received intramuscularly (RR, 0.74; 95% CI, 0.47–1.17; p = 0.20), intravenously (RR, 0.97; 95% CI, 0.51–1.83; p = 0.93), and orally (RR = 0.88; 95% CI, 0.55–0.1.43; p = 0.62). Conclusions Rectal administration of NSAIDs (both indomethacin and diclofenac) was effective in preventing PEP in unselected patients. A single dose of indomethacin after ERCP might be effective in preventing PEP in both high-risk and average-risk patients. However, diclofenac administered rectally before ERCP might be protective against PEP in high-risk patients compared to a placebo. However, more high quality head-to-head RCTs are required.
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Affiliation(s)
- Yunxiao Lyu
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China.
| | - Yunxiao Cheng
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
| | - Bin Wang
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
| | - Yueming Xu
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
| | - Weibing Du
- Department of General Surgery, Dongyang people's Hospital, Dongyang, 322100, Zhejiang Province, China
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13
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Gooshe M, Abdolghaffari AH, Nikfar S, Mahdaviani P, Abdollahi M. Antioxidant therapy in acute, chronic and post-endoscopic retrograde cholangiopancreatography pancreatitis: An updated systematic review and meta-analysis. World J Gastroenterol 2015; 21:9189-9208. [PMID: 26290647 PMCID: PMC4533052 DOI: 10.3748/wjg.v21.i30.9189] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 04/15/2015] [Accepted: 06/15/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the efficacy and adverse effects of antioxidant therapy in acute pancreatitis (AP), chronic pancreatitis (CP) and post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). METHODS PubMed, Scopus, Google Scholar, Cochrane library database, and Evidence-based medicine/clinical trials published before August 2014 were searched. Clinical and laboratory outcomes of randomized trials of antioxidant therapy in patients with AP, CP and PEP were included. The methodological quality of the trials was assessed by the Jadad score based on the description of randomization, blinding, and dropouts (withdrawals). The results of the studies were pooled and meta-analyzed to provide estimates of the efficacy of antioxidant therapy. RESULTS Thirty four trials out of 1069 potentially relevant studies with data for 4898 patients were eligible for inclusion. Antioxidant therapy significantly reduced the length of hospital stay in AP patients {mean difference -2.59 d (95%CI: -4.25-(-0.93)], P = 0.002}. Although, antioxidant therapy had no significant effect on serum C reactive protein (CRP) after 5-7 d in AP patients [mean difference -9.57 (95%CI: -40.61-21.48, P = 0.55], it significantly reduced serum CRP after 10 d {mean difference -45.16 [95%CI: -89.99-(-0.33)], P = 0.048}. In addition, antioxidant therapy had no significant effect on CP-induced pain [mean difference -2.13 (95%CI: -5.87-1.6), P = 0.26]. Antioxidant therapy had no significant effects on the incidence of all types of PEP [mean difference 1.05 (95%CI: 0.74-1.5), P = 0.78], severe PEP [mean difference 0.92 (95%CI: 0.43-1.97), P = 0.83], moderate PEP [mean difference 0.82 (95%CI: 0.54-1.23), P = 0.33], and mild PEP [mean difference 1.33 (95%CI: 0.99-1.78), P = 0.06]. Furthermore, while antioxidant therapy had no significant effect on serum amylase after less than 8 h sampling [mean difference -20.61 (95%CI: -143.61-102.39), P = 0.74], it significantly reduced serum amylase close to 24-h sampling {mean difference -16.13 [95%CI: -22.98-(-9.28)], P < 0.0001}. CONCLUSION While there is some evidence to support antioxidant therapy in AP, its effect on CP and PEP is still controversial.
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14
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Fuentes-Orozco C, Dávalos-Cobián C, García-Correa J, Ambriz-González G, Macías-Amezcua MD, García-Rentería J, Rendón-Félix J, Chávez-Tostado M, Cuesta-Márquez LA, Alvarez-Villaseñor AS, Cortés-Flores AO, González-Ojeda A. Antioxidant drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis: What does evidence suggest? World J Gastroenterol 2015; 21:6745-6753. [PMID: 26074713 PMCID: PMC4458785 DOI: 10.3748/wjg.v21.i21.6745] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Revised: 01/30/2015] [Accepted: 04/28/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine whether or not the use of antioxidant supplementation aids in the prevention of post- endoscopic retrograde cholangiopancreatography pancreatitis.
METHODS: A systematic review of randomized controlled trials (RCTs) was made to evaluate the preventive effect of prophylactic antioxidant supplementation in post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The inclusion criteria included: acute post-endoscopic retrograde cholangiopancreatography pancreatitis in adults; randomized clinical trials with the use of any antioxidant as an intervention compared with placebo, to reduce PEP. The outcome measure was the incidence and severity of PEP. Twelve RCTs involving 3110 patients since 1999 were included. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), N-acetylcysteine (NAC) in three trials, and allopurinol in six trials. The group of patients treated with NAC received different doses; either oral or intravenous, and allopurinol-treated patients received five different oral doses in two different administration periods. The results are expressed with raw numbers, proportions, as well as mean and standard deviations. The incidence of pancreatitis between groups was analyzed with Pearson’s χ2 test or Fisher’s exact test (F). The main outcome is expressed as relative risks and 95%CI.
RESULTS: The incidence of pancreatitis in all antioxidant treatment groups was 8.6%, whereas it was 9.7% in the control group. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), NAC in three trials, and allopurinol in six trials. In allopurinol trials, three different dosifications were used; two trials reported a low dosage (of less than 400 mg), two trials reported a moderate dose (600 mg) and the remaining two employed higher doses (more than 900 mg). Supplementation was not associated with a significant reduction in the incidence of PEP [relative risk (RR) = 0.93; 95%CI: 0.82-1.06; P = 0.28]. In addition, the incidences of PEP in patients treated with allopurinol and those treated with other antioxidants were similar to that observed in patients who received the placebo (RR for trials with allopurinol, 0.92; 95%CI: 0.78-1.08; P = 0.31) and, with the use of other antioxidants, the incidence of PEP was 8.9%, whereas it was 9.7% in the control group (RR = 0.95; 95%CI: 0.77-1.18; P = 0.19).
CONCLUSION: Antioxidant supplementation shows no beneficial effect on the incidence of PEP. There is a lack of robust trials to support the use of antioxidants for prevention.
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15
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Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. Gastrointest Endosc 2015; 81:143-149.e9. [PMID: 25088919 DOI: 10.1016/j.gie.2014.06.045] [Citation(s) in RCA: 321] [Impact Index Per Article: 32.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Accepted: 06/26/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Data regarding the incidence and severity of post-ERCP pancreatitis (PEP) are primarily from nonrandomized studies. OBJECTIVE To determine the incidence, severity, and mortality of PEP from a systematic review of the placebo or no-stent arms of randomized, controlled trials (RCTs). DESIGN MEDLINE, EMBASE, and Cochrane databases were searched to identify RCTs evaluating the efficacy of drugs and/or pancreatic stents to prevent PEP. SETTING Systematic review of patients enrolled in RCTs evaluating agents for PEP prophylaxis. PATIENTS Patients in the placebo or no-stent arms of the RCTs INTERVENTION ERCP. MAIN OUTCOME MEASUREMENTS Incidence, severity, and mortality of PEP. RESULTS There were 108 RCTs with 13,296 patients in the placebo or no-stent arms. Overall, the PEP incidence was 9.7% and the mortality rate was 0.7%. Severity of PEP was reported for 8857 patients: 5.7%, 2.6%, and 0.5% of cases were mild, moderate, and severe, respectively. The incidence of PEP in 2345 high-risk patients was 14.7% and the severity of PEP was mild, moderate, and severe in 8.6%, 3.9%, and 0.8%, respectively, with a 0.2% mortality rate. The incidence of PEP was 13% in North American RCTs compared with 8.4% in European and 9.9% in Asian RCTs. ERCPs conducted before and after 2000 had a PEP incidence of 7.7% and 10%, respectively. LIMITATIONS Difference in PEP risk among patients in the included RCTs. CONCLUSION The incidence of PEP and severe PEP is similar in high-risk patients and the overall cohort. Discrepancies in the incidence of PEP across geographic regions require further study.
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16
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Lee TH, Park DH. Endoscopic prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. World J Gastroenterol 2014; 20:16582-16595. [PMID: 25469026 PMCID: PMC4248201 DOI: 10.3748/wjg.v20.i44.16582] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Revised: 03/11/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is not an uncommon adverse event but may be an avoidable complication. Although pancreatitis of severe grade is reported in 0.1%-0.5% of ERCP patients, a serious clinical course may be lethal. For prevention of severe PEP, patient risk stratification, appropriate selection of patients using noninvasive diagnostic imaging methods such as magnetic resonance cholangiopancreatography or endoscopic ultrasonography (EUS), and avoidance of unnecessary invasive procedures, are important measures to be taken before any procedure. Pharmacological prevention is also commonly attempted but is usually ineffective. No ideal agent has not yet been found and the available data conflict. Currently, rectal non-steroidal anti-inflammatory drugs are used to prevent PEP in high-risk patients, but additional studies using larger numbers of subjects are necessary to confirm any prophylactic effect. In this review, we focus on endoscopic procedures seeking to prevent or decrease the severity of PEP. Among various cannulation methods, wire-guided cannulation, precut fistulotomy, and transpancreatic septostomy are reviewed. Prophylactic pancreatic stent placement, which is the best-known prophylactic method, is reviewed with reference to the ideal stent type, adequate duration of stent placement, and stent-related complications. Finally, we comment on other treatment alternatives, and make the point that further advances in EUS-guided techniques may afford useful PEP prophylaxis.
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17
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Akinosoglou K, Gogos C. Immune-modulating therapy in acute pancreatitis: Fact or fiction. World J Gastroenterol 2014; 20:15200-15215. [PMID: 25386069 PMCID: PMC4223254 DOI: 10.3748/wjg.v20.i41.15200] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2014] [Revised: 05/21/2014] [Accepted: 06/17/2014] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, bearing significant morbidity and mortality worldwide. Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care. As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis, therapeutic approaches have turned towards modulating the systemic inflammatory response. Targets, among others, have included pro- and anti-inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules and platelets. Even though, initial results in experimental models have been encouraging, clinical implementation of immune-regulating therapies in acute pancreatitis has had a slow progress. Main reasons include difficulty in clinical translation of experimental data, poor understanding of inflammatory response time-course, flaws in experimental designs, need for multimodal approaches and commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future.
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18
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Prevention effect of allopurinol on post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of prospective randomized controlled trials. PLoS One 2014; 9:e107350. [PMID: 25202907 PMCID: PMC4159328 DOI: 10.1371/journal.pone.0107350] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2014] [Accepted: 08/14/2014] [Indexed: 01/07/2023] Open
Abstract
Background Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) which can be severe and cause death in approximately 10% of cases. Up to now, six randomized controlled trials (RCTs) have been found relevant to the effect of allopurinol on prevention of Post-ERCP pancreatitis (PEP). However, these results remained controversial. Objective To conduct a meta-analysis with RCTs published in full text to determine the effectiveness of prophylactic allopurinol of different dosages and administration time in the incidence and severity of PEP. Methods Literature search was performed in PubMed, Embase, Web of Science and Cochrane Library from databases inception to May 2014. RCTs comparing the effect of allopurinol with placebo on prevention of PEP were included. Statistical heterogeneity was quantitatively evaluated byχ2 test with the significance set P<0.10 or I2>50%. Results Six RCTs consisting of 1974 participants were eventually included. The incidences of PEP in allopurinol group and placebo group were 8.4%(83/986) and 9.9%(98/988) respectively. Meta-analysis showed no evident prevention effect of allopurinol on the incidence of PEP (RR 0.75, 95%CI 0.39–1.42) with significant heterogeneity (I2 = 70.4%, P = 0.005). When studies were stratified according to the dosages and administration time of allopurinol they applied, there was still no evident prevention effect of allopurinol on mild, moderate or severe PEP. However, statistically substantial heterogeneity was presented in the subgroup of moderate PEP when the effect of high dose of allopurinol was analyzed (Imoderate2 = 82.3%, Pmoderate = 0.018). Statistically significant heterogeneity was also observed in subgroup of mild PEP, when the effect of long adminstration time of allopurinol was investigated (Imild2 = 62.8%, Pmild = 0.068). Conclusion The prophylactic use of allopurinol in different dosages and administration time had no effect in preventing incidence and severity of PEP.
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Abstract
Post-procedure pancreatitis is the most common complication of endoscopic retrograde cholangio pancreatography (ERCP) and carries a high morbidity and mortality occurring in at least 3%-5% of all procedures. We reviewed the available literature searching for "ERCP" and "pancreatitis" and "post-ERCP pancreatitis". in PubMed and Medline. This review looks at the diagnosis, risk factors, causes and methods of preventing post-procedure pancreatitis. These include the evidence for patient selection, endoscopic techniques and pharmacological prophylaxis of ERCP induced pancreatitis. Selecting the right patient for the procedure by a risk benefits assessment is the best way of avoiding unnecessary ERCPs. Risk is particularly high in young women with sphincter of Oddi dysfunction (SOD). Many of the trials reviewed have rather few numbers of subjects and hence difficult to appraise. Meta-analyses have helped screen for promising modalities of prophylaxis. At present, evidence is emerging that pancreatic stenting of patients with SOD and rectally administered nonsteroidal anti-inflammatory drugs in a large unselected trial reduce the risk of post-procedure pancreatitis. A recent meta-analysis have demonstrated that rectally administered indomethecin, just before or after ERCP is associated with significantly lower rate of pancreatitis compared with placebo [OR = 0.49 (0.34-0.71); P = 0.0002]. Number needed to treat was 20. It is likely that one of these prophylactic measures will begin to be increasingly practised in high risk groups.
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Affiliation(s)
- Lin-Lee Wong
- Lin-Lee Wong, Her-Hsin Tsai, Department of Gastroenterology, Castle Hill Hospital, HEY NHS Trust and Hull York Medical School, Cottingham HU165JQ, United Kingdom
| | - Her-Hsin Tsai
- Lin-Lee Wong, Her-Hsin Tsai, Department of Gastroenterology, Castle Hill Hospital, HEY NHS Trust and Hull York Medical School, Cottingham HU165JQ, United Kingdom
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20
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The effect of indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis. Pancreas 2014; 43:338-42. [PMID: 24622061 DOI: 10.1097/mpa.0000000000000086] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is a severe complication with substantial morbidity and mortality. Indomethacin has been identified to prevent this complication; however, the results using indomethacin have varied. Therefore, we performed a meta-analysis on the efficacy of rectally administered indomethacin in the prevention of post-ERCP pancreatitis (PEP). METHODS A systematic search was performed in November 2012. Randomized, placebo-controlled trials (randomized controlled trials) in adult patients that compared rectally administered indomethacin versus placebo in prevention of PEP were included. Meta-analysis was performed using a fixed-effects model to assess the primary outcome (PEP) and secondary outcomes (mild or moderate to severe PEP) using Review Manager 5.1. RESULTS Four randomized controlled trials met the inclusion criteria (n = 1422). The use of indomethacin near the time of ERCP demonstrated a statistically significant decrease in PEP (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.34-0.71; P < 0.01), mild PEP (OR, 0.52; 95% CI, 0.32-0.86; P = 0.01), and moderate to severe PEP (OR, 0.45; 95% CI, 0.24-0.83; P = 0.01) as compared with placebo. The number needed to treat with indomethacin to prevent 1 episode of pancreatitis is 17 patients. CONCLUSIONS Rectal indomethacin significantly reduced the incidence of PEP. We recommend using indomethacin before or just after the procedure in patients undergoing ERCP.
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Wong LL, Tsai HH. Prevention of post-ERCP pancreatitis. World J Gastrointest Pathophysiol 2014; 5:1-10. [PMID: 24891970 PMCID: PMC4024515 DOI: 10.4291/wjgp.v5.i1.1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 10/26/2013] [Accepted: 01/14/2014] [Indexed: 02/06/2023] Open
Abstract
Post-procedure pancreatitis is the most common complication of endoscopic retrograde cholangio pancreatography (ERCP) and carries a high morbidity and mortality occurring in at least 3%-5% of all procedures. We reviewed the available literature searching for “ERCP” and “pancreatitis” and “post-ERCP pancreatitis”. in PubMed and Medline. This review looks at the diagnosis, risk factors, causes and methods of preventing post-procedure pancreatitis. These include the evidence for patient selection, endoscopic techniques and pharmacological prophylaxis of ERCP induced pancreatitis. Selecting the right patient for the procedure by a risk benefits assessment is the best way of avoiding unnecessary ERCPs. Risk is particularly high in young women with sphincter of Oddi dysfunction (SOD). Many of the trials reviewed have rather few numbers of subjects and hence difficult to appraise. Meta-analyses have helped screen for promising modalities of prophylaxis. At present, evidence is emerging that pancreatic stenting of patients with SOD and rectally administered nonsteroidal anti-inflammatory drugs in a large unselected trial reduce the risk of post-procedure pancreatitis. A recent meta-analysis have demonstrated that rectally administered indomethecin, just before or after ERCP is associated with significantly lower rate of pancreatitis compared with placebo [OR = 0.49 (0.34-0.71); P = 0.0002]. Number needed to treat was 20. It is likely that one of these prophylactic measures will begin to be increasingly practised in high risk groups.
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Akshintala VS, Hutfless SM, Colantuoni E, Kim KJ, Khashab MA, Li T, Elmunzer BJ, Puhan MA, Sinha A, Kamal A, Lennon AM, Okolo PI, Palakurthy MK, Kalloo AN, Singh VK. Systematic review with network meta-analysis: pharmacological prophylaxis against post-ERCP pancreatitis. Aliment Pharmacol Ther 2013; 38:1325-37. [PMID: 24138390 DOI: 10.1111/apt.12534] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2013] [Revised: 08/03/2013] [Accepted: 09/29/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND The efficacy of many pharmacological agents for preventing post-ERCP pancreatitis (PEP) has been evaluated in randomised controlled trials (RCTs), but it is unclear which agent(s) should be used in clinical practice. Network meta-analyses of RCTs are used to simultaneously compare several agents to determine their relative efficacy and identify priority agents for comparison in future RCTs. AIM To evaluate pharmacological agents for the prevention of PEP by conducting a network meta-analysis of RCTs. METHODS We searched MEDLINE, EMBASE and Cochrane Library databases for RCTs that evaluated the efficacy of agents for preventing PEP. RCTs were simultaneously analysed using random-effects network meta-analysis under the Bayesian framework to identify the best agents. The efficacy of agents was ordered according to the probability of being ranked as any of the top three best performing agents. RESULTS The network meta-analysis included 99 RCTs evaluating 16 agents in 25 313 patients. Topical epinephrine (adrenaline) was the most efficacious agent with 85.9% probability of ranking among the top three agents, followed by nafamostat (51.4%), antibiotics (44.5%) and NSAIDs (42.8%). However, in a sensitivity analysis including only rectal NSAIDs, NSAIDs moved from fourth rank to second (58.1%). Patients receiving topical epinephrine, compared with placebo, had a 75% reduced risk of PEP (OR 0.25, 95% probability interval 0.06-0.66). CONCLUSIONS Topical epinephrine and rectal NSAIDs are the most efficacious agents for preventing post-ERCP pancreatitis, based on existing RCTs. Combinations of these agents, which act on different steps in the pathogenesis of post-ERCP pancreatitis, should be evaluated in future trials.
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Affiliation(s)
- V S Akshintala
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
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Law R, Leal C, Dayyeh BA, Leise MD, Balderramo D, Baron TH, Cardenas A. Role of immunosuppression in post-endoscopic retrograde cholangiopancreatography pancreatitis after liver transplantation: a retrospective analysis. Liver Transpl 2013; 19:1354-60. [PMID: 24115362 DOI: 10.1002/lt.23758] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Accepted: 08/27/2013] [Indexed: 12/11/2022]
Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) is frequently used for diagnosis and therapeutic interventions in recipients of liver transplantation (LT) who develop biliary complications. Post-endoscopic retrograde cholangiopancreatography acute pancreatitis (PEP) is the most common major adverse event after ERCP; however, the frequency of PEP in LT recipients is not well established. We aimed to determine the rate of PEP in this population and to identify its predictors, especially among immunosuppressive agents. We reviewed all ERCP procedures performed in LT recipients after duct-to-duct biliary anastomoses at 2 high-volume transplant centers. Patients who had undergone sphincterotomy or had a surgically altered pancreaticobiliary anatomy before LT were excluded. Electronic medical records and endoscopy databases were used to obtain clinical, endoscopic, and medication data. A multivariate logistic regression analysis was used to determine predictors of PEP in this cohort. In all, 730 ERCP procedures were performed in 301 patients during the study period with an observed PEP rate of 3% (22/730). A univariate analysis revealed an increased risk of PEP with index ERCP after LT [odds ratio (OR) = 4.04, 95% confidence interval (CI) = 1.40-11.65] and in cases with difficult biliary cannulation (OR = 2.89, 95% CI = 1.10-7.65), whereas prednisone use was found to have a protective effect in both univariate (OR = 0.34, 95% CI = 0.14-0.84) and multivariate analyses (OR = 0.22, 95% CI = 0.09-0.57) after adjustments for difficult biliary cannulation and post-LT index ERCP. This retrospective analysis demonstrates that corticosteroid therapy has a protective role in the development of PEP in LT recipients. Further studies are warranted to confirm our findings.
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Affiliation(s)
- Ryan Law
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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Abstract
There is a convincing body of evidence that oxidative stress is involved in the pathogenesis of acute pancreatitis. The effects of different radical scavengers suggested that reactive oxygen metabolites are generated at very early stage of disease and contribute to amplify the pancreatic damage. Oxidative stress is also involved in the progression of the disease from a local damage to a systemic organ failure. However, therapeutic use of antioxidants failed to clearly show a clinical benefit in different trials. Therefore, although antioxidants alone seem to be not enough for the treatment of severe acute pancreatitis, future combined therapeutic strategies should include antioxidants in its composition.
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Affiliation(s)
- Daniel Closa
- Department of Experimental Pathology, IIBB-CSIC-IDIBAPS, CIBEREHD , Barcelona , Spain
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Cheon YK. Can postendoscopic retrograde cholangiopancreatography pancreatitis be prevented by a pharmacological approach? Korean J Intern Med 2013; 28:141-8. [PMID: 23525264 PMCID: PMC3604601 DOI: 10.3904/kjim.2013.28.2.141] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Accepted: 12/14/2012] [Indexed: 02/07/2023] Open
Abstract
Acute pancreatitis remains the most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP), with reported incidence rates that have changed little over several decades. Patient- and procedure-related risk factors for post-ERCP pancreatitis (PEP) are well-defined. Effective measures to prevent PEP have been identified, including improvements in cannulation techniques and pancreatic stenting, as well as pharmacological intervention. Pharmacotherapy has been widely studied in the prevention of PEP, but the effect in averting PEP has been inconclusive. Although pharmacological prophylaxis is appealing, attempts to find an ideal drug are incomplete. Most available data on the efficacy of pharmacological agents for PEP prophylaxis have been obtained from patients at average risk for PEP. However, recently, a randomized prospective controlled trial of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent PEP in high-risk patients was published. The results revealed that rectal indomethacin reduced the incidence of PEP significantly. Thus, rectal administration of diclofenac or indomethacin immediately before or after ERCP is used routinely to prevent PEP. However, additional studies with NSAIDs using large numbers of subjects are necessary to confirm the prophylactic effect of these drugs and to establish whether they act synergistically with other prophylactic interventions, including pancreatic stenting.
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Affiliation(s)
- Young Koog Cheon
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
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Gu WJ, Wei CY, Yin RX. Antioxidant supplementation for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials. Nutr J 2013; 12:23. [PMID: 23398675 PMCID: PMC3575286 DOI: 10.1186/1475-2891-12-23] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2012] [Accepted: 01/25/2013] [Indexed: 02/07/2023] Open
Abstract
Background Acute pancreatitis remains the most common major complication of endoscopic retrograde cholangiopancreatography (ERCP). The pathogenesis of post-ERCP acute pancreatitis may be mediated by oxygen-derived free radicals, which could be ameliorated by antioxidants. Antioxidant supplementation may potentially prevent post-ERCP pancreatitis. We performed a meta-analysis of randomized controlled trials to evaluate the effect of prophylactic antioxidant supplementation compared with control on the prevention of post-ERCP pancreatitis. Methods PubMed and Embase databases were searched to identify relevant trials. A standardized Excel file was used to extract data by two independent authors. Results were expressed as risk ratio (RR) with accompanying 95% confidence interval (CI). The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. Results Eleven studies involving 3,010 patients met our inclusion criteria. Antioxidant supplementation did not significantly decrease the incidence of post-ERCP pancreatitis (RR, 0.92; 95% CI, 0.65-1.32; P = 0.665). There was also no statistical difference in the severity grades between the antioxidant group and control group. Conclusions Based on current evidence, antioxidant supplementation shows no beneficial effect on the incidence and the severity of post-ERCP pancreatitis; thus, there is currently a lack of evidence to support using antioxidants for the prevention of post-ERCP pancreatitis.
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Affiliation(s)
- Wan-Jie Gu
- Department of Anaesthesiology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
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Thorlacius H. Author's reply: P-selectin mediates neutrophil rolling and recruitment in acute pancreatitis ( Br J Surg 2012; 99: 246–255). Br J Surg 2012. [DOI: 10.1002/bjs.8901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- H Thorlacius
- Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden
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Woods KE, Willingham FF. Endoscopic retrograde cholangiopancreatography associated pancreatitis: A 15-year review. World J Gastrointest Endosc 2010; 2:165-78. [PMID: 21160744 PMCID: PMC2998911 DOI: 10.4253/wjge.v2.i5.165] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2010] [Revised: 04/29/2010] [Accepted: 05/06/2010] [Indexed: 02/06/2023] Open
Abstract
The aim of this article is to review the literature regarding post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We searched for and evaluated all articles describing the diagnosis, epidemiology, pathophysiology, morbidity, mortality and prevention of post-ERCP pancreatitis (PEP) in adult patients using the PubMed database. Search terms included endoscopic retrograde cholangiopancreatography, pancreatitis, ampulla of vater, endoscopic sphincterotomy, balloon dilatation, cholangiography, adverse events, standards and utilization. We limited our review of articles to those published between January 1, 1994 and August 15, 2009 regarding human adults and written in the English language. Publications from the reference sections were reviewed and included if they were salient and fell into the time period of interest. Between the dates queried, seventeen large (> 500 patients) prospective and four large retrospective trials were conducted. PEP occurred in 1%-15% in the prospective trials and in 1%-4% in the retrospective trials. PEP was also reduced with pancreatic duct stent placement and outcomes were improved with endoscopic sphincterotomy compared to balloon sphincter dilation in the setting of choledocholithiasis. Approximately 34 pharmacologic agents have been evaluated for the prevention of PEP over the last fifteen years in 63 trials. Although 22 of 63 trials published during our period of review suggested a reduction in PEP, no pharmacologic therapy has been widely accepted in clinical use in decreasing the development of PEP. In conclusion, PEP is a well-recognized complication of ERCP. Medical treatment for prevention has been disappointing. Proper patient selection and pancreatic duct stenting have been shown to reduce the complication rate in randomized clinical trials.
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Affiliation(s)
- Kevin E Woods
- Kevin E Woods, Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
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Monfared SSMS, Vahidi H, Abdolghaffari AH, Nikfar S, Abdollahi M. Antioxidant therapy in the management of acute, chronic and post-ERCP pancreatitis: a systematic review. World J Gastroenterol 2009; 15:4481-4490. [PMID: 19777606 PMCID: PMC2751992 DOI: 10.3748/wjg.15.4481] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2009] [Revised: 08/03/2009] [Accepted: 08/10/2009] [Indexed: 02/06/2023] Open
Abstract
We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis. Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis (AP) or chronic pancreatitis (CP) and in the prevention of post-endoscopic retrograde cholangio-pancreatography (post-ERCP) pancreatitis (PEP) up to February 2009. Twenty-two randomized, placebo-controlled, clinical trials met our criteria and were included in the review. Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials, the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous. Furthermore, antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials. In conclusion, the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP, CP or PEP. Further double blind, randomized, placebo-controlled clinical trials with large sample size need to be conducted.
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Cennamo V, Fuccio L, Zagari RM, Eusebi LH, Ceroni L, Laterza L, Fabbri C, Bazzoli F. Can a wire-guided cannulation technique increase bile duct cannulation rate and prevent post-ERCP pancreatitis?: A meta-analysis of randomized controlled trials. Am J Gastroenterol 2009; 104:2343-50. [PMID: 19532133 DOI: 10.1038/ajg.2009.269] [Citation(s) in RCA: 105] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The most common technique used to achieve primary deep biliary cannulation is the standard contrast-assisted method. To increase the success rate and reduce the risk of complications, a wire-guided cannulation strategy has been proposed. Prospective studies provided conflicting results as to whether the wire-guided cannulation technique increases the cannulation rate and reduces post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis risk compared with the standard method. The objective of this study was to carry out a meta-analysis of randomized controlled trials (RCTs) that compares primary biliary cannulation and post-ERCP pancreatitis rates with the wire-guided method and the standard cannulation technique. METHODS Literature searches of electronic databases and online clinical trial registers up to March 2009 were conducted to identify RCTs comparing primary cannulation and post-ERCP pancreatitis rates with the wire-guided method and the standard cannulation technique. A meta-analysis of these clinical trials was performed. RESULTS Five RCTs were included. Overall, the primary cannulation rates reported with the wire-guided cannulation technique and the standard method were 85.3 and 74.9%, respectively. The pooled analysis of all the selected studies comparing the wire-guided cannulation technique with the standard method yielded an odds ratio (OR) of 2.05 (95% confidence interval (CI): 1.27-3.31). The pooled analysis comparing the post-ERCP pancreatitis rates for the wire-guided-cannulation groups with those for the standard-method groups yielded an OR of 0.23 (95% CI: 0.13-0.41). CONCLUSIONS This meta-analysis shows that the wire-guided technique increases the primary cannulation rate and reduces the risk of post-ERCP pancreatitis compared with the standard contrast-injection method. Further large, well-performed, randomized controlled studies are needed to confirm these findings.
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Affiliation(s)
- Vincenzo Cennamo
- Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna 40138, Italy
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Martinez-Torres H, Rodriguez-Lomeli X, Davalos-Cobian C, Garcia-Correa J, Maldonado-Martinez JM, Medrano-Muñoz F, Fuentes-Orozco C, Gonzalez-Ojeda A. Oral allopurinol to prevent hyperamylasemia and acute pancreatitis after endoscopic retrograde cholangiopancreatography. World J Gastroenterol 2009; 15:1600-6. [PMID: 19340902 PMCID: PMC2669944 DOI: 10.3748/wjg.15.1600] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the efficacy of allopurinol to prevent hyperamylasemia and pancreatitis after endoscopic retrograde cholangiopancreatography (PEP).
METHODS: One hundred and seventy patients were enrolled and randomized to two groups: a study group (n = 85) who received 300 mg of oral allopurinol at 15 h and 3 h before endoscopic retrograde cholangiopancreatography (ERCP) and a control group (n = 85) receiving an oral placebo at the same times. Main Outcome Measurements included serum amylase levels and the number severity of the episodes of pancreatitis. Serum amylase levels were classified as normal (< 150 IU/L) or hyperamylasemia (> 151 IU/L). Episodes of PEP were classified following Ranson’s criteria and CT severity index.
RESULTS: Gender distribution was similar between groups. Mean age was 53.5 ± 18.9 years for study group and 52.8 ± 19.8 years for controls. Also, the distribution of benign pathology was similar between groups. Hyperamylasemia was more common in the control group (P = 0.003). Mild PEP developed in two patients from the study group (2.3%) and eight (9.4%) from control group (P = 0.04), seven episodes were observed in high-risk patients of the control group (25%) and one in the allopurinol group (3.3%, P = 0.02). Risk factors for PEP were precut sphincterotomy (P = 0.02), pancreatic duct manipulation (P = 0.002) and multiple procedures (P = 0.000). There were no deaths or side effects.
CONCLUSION: Oral allopurinol before ERCP decreased the incidences of hyperamylasemia and pancreatitis in patients submitted to high-risk procedures.
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Sherman S, Alazmi WM, Lehman GA, Geenen JE, Chuttani R, Kozarek RA, Welch WD, Souza S, Pribble J. Evaluation of recombinant platelet-activating factor acetylhydrolase for reducing the incidence and severity of post-ERCP acute pancreatitis. Gastrointest Endosc 2009; 69:462-472. [PMID: 19231487 DOI: 10.1016/j.gie.2008.07.040] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2006] [Accepted: 07/22/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. Platelet-activating factor (PAF) has been implicated in the pathophysiologic events associated with acute pancreatitis. Animal and human studies suggested that recombinant PAF acetylhydrolase (rPAF-AH) might ameliorate the severity of acute pancreatitis. OBJECTIVE Our purpose was to determine whether prophylactic rPAF-AH administration reduces the frequency or severity of post-ERCP pancreatitis in high-risk patients. DESIGN Randomized, multicenter, double-blind, placebo-controlled study. INTERVENTIONS Patients received rPAF-AH at a dose of either 1 or 5 mg/kg or placebo. Patients were administered a single intravenous infusion over 10 minutes of study drug or placebo <1 hour before ERCP. MAIN OUTCOME MEASUREMENTS Standardized criteria were used to diagnose and grade the severity of post-ERCP pancreatitis. Adverse events were prospectively recorded. RESULTS A total of 600 patients were enrolled. There were no statistically significant differences among the treatment groups with respect to patient demographics, ERCP indications, and patient and procedure risk factors for post-ERCP pancreatitis with the following exceptions: the rPAF-AH 5 mg/kg group had significantly fewer patients younger than 40 years old and scheduled to undergo a therapeutic ERCP involving the pancreatic sphincter or duct. Post-ERCP pancreatitis occurred in 17.5%, 15.9%, and 19.6% of patients receiving rPAF-AH (1 mg/kg), rPAF-AH (5 mg/kg), and placebo, respectively (P = .59 for rPAF-AH 1 mg/kg vs placebo and P = .337 for rPAF-AH 5 mg/kg vs placebo). There was no statistically significant difference between the groups with regard to the severity of pancreatitis, frequency of amylase/lipase elevation more than 3 times normal, or abdominal pain. CONCLUSIONS There was no apparent benefit of rPAF-AH treatment compared with placebo in reducing the incidence of post-ERCP pancreatitis in subjects at increased risk.
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Affiliation(s)
- Stuart Sherman
- Indiana University Medical Center, Indianapolis, Indiana, USA
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Abstract
Reactive oxygen and reactive nitrogen species (ROS/RNS) have been implicated in the pathogenesis of acute and chronic pancreatitis. Clinical and basic science studies have indicated that ROS/RNS formation processes are intimately linked to the development of the inflammatory disorders. The detrimental effects of highly reactive ROS/RNS are mediated by their direct actions on biomolecules (lipids, proteins, and nucleic acids) and activation of proinflammatory signal cascades, which subsequently lead to activation of immune responses. The present article summarizes the possible sources of ROS/RNS formation and the detailed signaling cascades implicated in the pathogenesis of pancreatic inflammation, as observed in acute and chronic pancreatitis. A therapeutic ROS/RNS-scavenging strategy has been advocated for decades; however, clinical studies examining such approaches have been inconsistent in their results. Emerging evidence indicates that pancreatitis-inducing ROS/RNS generation may be attenuated by targeting ROS/RNS-generating enzymes and upstream mediators.
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Affiliation(s)
- Po Sing Leung
- Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
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Nakaji K, Suzumura S, Nakae Y, Kojima K, Kumamoto M, Kozu T. Effects in the control of edema of the papilla of Vater by epinephrine saline irrigation after endoscopic retrograde cholangiopancreatography in an endoscopy center in Japan, 2003 to 2007: exploratory retrospective analysis to evaluate the characteristics of eligible patients with a focus on serum amylase levels. Intern Med 2009; 48:945-52. [PMID: 19525579 DOI: 10.2169/internalmedicine.48.1705] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE To evaluate the effects of localized irrigation with epinephrine saline after endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS One hundred and fourteen patients who underwent ERCP in our institute were treated with or without irrigation using epinephrine diluted in saline after ERCP to prevent post-ERCP pancreatitis. The serum amylase levels, white blood cell counts, and urine amylase levels were measured at 24 and 48 hours after ERCP. RESULTS The treatment resulted in improvements in all items. A univariate analysis of the explanatory variables between the treatment and untreated groups revealed the treatment to be effective, but not statistically significant. Gender and cannulation of the pancreatic duct were the only variables with significant partial regression coefficients in the multiple regression model with all explanatory variables (p=0.045). When a stratified analysis was conducted using gender as a moderator variable, the treatment became a significant preventive factor (p=0.038), and cannulation of the pancreatic duct was a significant risk factor (p=0.027) in female patients. CONCLUSION We suggest that irrigating with epinephrine saline into the papilla may be effective for preventing pancreatitis in female patients who received ERCP with cannulation of their pancreatic duct.
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Abstract
Acute pancreatitis has an incidence of about 300 per 1 million individuals per year, of which 10-15% of patients develop the severe form of the disease. Novel management options, which have the potential to improve outcome, include initial proper fluid resuscitation, which maintains microcirculation and thereby potentially decreases ischaemia and reperfusion injury. The traditional treatment concept in acute pancreatitis, fasting and parenteral nutrition, has been challenged and early initiation of enteral feeding in severe pancreatitis and oral intake in mild acute pancreatitis is both feasible and provides some benefits. There are at present no data supporting immunonutritional supplements and probiotics should be avoided in patients with acute pancreatitis. There is also no evidence of any benefits provided by prophylactic antibacterials in patients with predicted severe acute pancreatitis. A variety of specific medical interventions have been investigated (e.g. intense blood glucose monitoring by insulin) but none has become clinically useful. Lessons can probably be learned from critical care in general, but studies are needed to verify these interventions in acute pancreatitis.
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Affiliation(s)
- Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Lund University Hospital, Lund, Sweden.
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Chan HH, Lai KH, Lin CK, Tsai WL, Lo GH, Hsu PI, Wei MC, Wang EM. Effect of somatostatin in the prevention of pancreatic complications after endoscopic retrograde cholangiopancreatography. J Chin Med Assoc 2008; 71:605-609. [PMID: 19114324 DOI: 10.1016/s1726-4901(09)70002-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The unique clinical role of endoscopic retrograde cholangiopancreatography (ERCP) in diagnosing and treating biliary tree diseases cannot be completely replaced by other modern imaging modalities such as magnetic resonance cholangiopancreatography. However, post-ERCP pancreatitis is one of the most common and life-threatening complications. Prophylactic medication in the prevention of pancreatitis during ERCP is still controversial. The objective of the present study was to investigate the role of different regimens of somatostatin in the prevention of acute pancreatitis after ERCP and analyze the risk factors contributing to post-ERCP complications. METHODS From July 1999 to September 2000, 133 patients with benign biliary disease who received ERCP for diagnosis or treatment were enrolled. Group A patients received a bolus of somatostatin infusion before ERCP, followed by continuous infusion for 12 hours. Group B patients received a bolus of somatostatin before ERCP only, and group C patients were the controls who did not receive somatostatin treatment. Serum amylase levels before and 24 hours after ERCP, and abdominal pain were recorded. RESULTS There were no significant differences in bile duct and pancreatic duct visualization, ratio of diagnostic and therapeutic ERCP, procedure time, post-procedural hyperamylasemia and pancreatitis among the 3 groups. For patients with visualization of the pancreatic duct, the incidences of hyperamylasemia (serum amylase > or = 220 U/L) were higher than in patients without visualization of the pancreatic duct (p < 0.001). All 6 patients with post-ERCP pancreatitis had pancreatic duct visualization, and recovered after conservative treatment. CONCLUSION Continuous infusion of somatostatin after ERCP does not seem to be helpful in the prevention of pancreatic complications after ERCP. Pancreatic duct visualization is a risk factor for pancreatic complications.
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Affiliation(s)
- Hoi-Hung Chan
- Division of Gastroenterology, Kaohsiung Veterans General Hospital, Kaohsiung, Taipei, Taiwan, ROC
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Preventive effects of ulinastatin on post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a prospective, randomized, placebo-controlled trial. Pancreas 2008; 37:366-70. [PMID: 18953247 DOI: 10.1097/mpa.0b013e31817f528f] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES Previous studies have shown that ulinastatin may be effective at preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, routine administration of ulinastatin is unlikely to be cost-effective. So the aim of this prospective study was to evaluate the effectiveness of low-dose ulinastatin at preventing pancreatitis in patients at high risk of post-ERCP pancreatitis. METHODS A total of 227 patients (mean age, 63 years; 54% men) were randomized to receive placebo (n = 108) or active drug (n = 119) immediately after ERCP and received active drug (100,000 U of ulinastatin) or placebo. Occurrence of post-ERCP pancreatitis and hyperamylasemia were compared between the 2 groups. RESULTS The overall incidence of pancreatitis was 6.2%, and no significant differences were observed between placebo- and ulinastatin-treated patients in terms of the frequencies of pancreatitis (5.6% vs 6.7%), abdominal pain, or hyperamylasemia. Pancreatic duct acinarization, papillectomy of ampulla of Vater adenoma, difficult cannulation, and female sex were identified as risk factors for pancreatitis in univariate analysis. CONCLUSIONS Low-dose prophylactic treatment with ulinastatin immediately after ERCP did not show a beneficial influence on the incidence of post-ERCP pancreatitis and hyperamylasemia in high-risk patients.
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Zheng M, Chen Y, Bai J, Xin Y, Pan X, Zhao L. Meta-analysis of prophylactic allopurinol use in post-endoscopic retrograde cholangiopancreatography pancreatitis. Pancreas 2008; 37:247-253. [PMID: 18815544 DOI: 10.1097/mpa.0b013e31816857e3] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED The aim of this study was to evaluate the effectiveness and the safety of allopurinol in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. METHODS : We used the method recommended by the Cochrane Collaboration to perform a meta-analysis of randomized controlled trials (RCTs) of allopurinol in the prevention of post-ERCP pancreatitis (PEP), including 6 RCTs conducted all over the world. RESULTS : Six RCTs totaling 1554 patients undergoing ERCP were included. When the RCTs were analyzed, odds ratios of allopurinol were 0.74 (95% confidence interval [CI], 0.37-1.48; P = 0.40) for PEP, 0.87 (95% CI, 0.33-2.28; P = 0.78) for severe PEP, 0.88 (95% CI, 0.37-2.11; P = 0.78) for post-ERCP hyperamylasemia, and 0.19 (95% CI, 0.01-3.91; P = 0.28) for case-fatality ratio of PEP, thus indicating no beneficial effects of allopurinol on acute pancreatitis, PEP death rate, and hyperamylasemia. No evidence of publication bias was found. CONCLUSIONS : Allopurinol cannot prevent the pancreatic injury after ERCP. Allopurinol is not recommended in the prophylaxis of PEP.
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Affiliation(s)
- Minghua Zheng
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
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Bai Y, Gao J, Shi X, Zou D, Li Z. Prophylactic corticosteroids do not prevent post-ERCP pancreatitis: a meta-analysis of randomized controlled trials. Pancreatology 2008; 8:504-9. [PMID: 18765955 DOI: 10.1159/000151999] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2007] [Accepted: 04/15/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND Data regarding the use of corticosteroids for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis are conflicting. The aim of this meta-analysis was to compare corticosteroids with placebo for prevention of post-ERCP pancreatitis. METHODS Multiple databases including MEDLINE, EMBASE, Cochrane controlled trials register, the Cochrane Library, Science Citation Index, Google Scholar and Google updated to June 2007 were searched to retrieve the relevant randomized controlled trials. Primary outcome measure was post-ERCP pancreatitis. RESULTS Six randomized controlled trials involving 2,448 patients were identified. The analysis showed that corticosteroids did not prevent post-ERCP pancreatitis (OR 1.13: 95% CI [0.88, 1.46]). Subsequent sensitivity and subgroup analyses according to different criteria all confirmed these results. CONCLUSIONS Based on available evidence, prophylactic corticosteroids do not reduce the incidence of post-ERCP pancreatitis.
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Affiliation(s)
- Yu Bai
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
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Bai Y, Gao J, Zhang W, Zou D, Li Z. Meta-analysis: allopurinol in the prevention of postendoscopic retrograde cholangiopancreatography pancreatitis. Aliment Pharmacol Ther 2008; 28:557-64. [PMID: 18714440 DOI: 10.1111/j.1365-2036.2008.03756.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Several clinical trials evaluating the prophylactic effect of allopurinol on postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis have been published; however, there is no consensus on whether prophylactic allopurinol can reduce the incidence of post-ERCP pancreatitis. AIM To compare prophylactic allopurinol with placebo on post-ERCP pancreatitis reduction by performing a meta-analysis in randomized controlled trials. METHODS Databases including MEDLINE, EMBASE and the Cochrane Library, Science Citation Index were searched to find relevant trials. Two reviewers independently identified relevant randomized controlled trials assessing the effect of prophylactic allopurinol on the incidence of post-ERCP pancreatitis. Outcome measures were the incidence of post-ERCP pancreatitis. RESULTS Four trials involving 1730 patients were included. Analysis suggested that post-ERCP pancreatitis rates were not significantly different (allopurinol 8.9%, placebo 9.7%, P = 0.68), RR 0.86 (95% CI: 0.42, 1.77). Subsequent subgroup analysis confirmed that allopurinol was not statistically superior to placebo in reducing post-ERCP pancreatitis. CONCLUSION Based on current best evidence, prophylactic allopurinol may not be useful for post-ERCP pancreatitis reduction.
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Affiliation(s)
- Y Bai
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
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Abstract
The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis (PEP). The protease inhibitor Gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha (TNF-α) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta-lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.
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Andriulli A, Annese V. Risk of post-endoscopic retrograde cholangiopancreatography pancreatitis and ways to prevent it: old myths, a current need? The case of allopurinol. Clin Gastroenterol Hepatol 2008; 6:374-376. [PMID: 18387495 DOI: 10.1016/j.cgh.2008.01.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Romagnuolo J, Hilsden R, Sandha GS, Cole M, Bass S, May G, Love J, Bain VG, McKaigney J, Fedorak RN. Allopurinol to prevent pancreatitis after endoscopic retrograde cholangiopancreatography: a randomized placebo-controlled trial. Clin Gastroenterol Hepatol 2008; 6:465-71; quiz 371. [PMID: 18304883 DOI: 10.1016/j.cgh.2007.12.032] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Endoscopic retrograde cholangiopancreatography (ERCP) is associated with a risk of pancreatitis (PEP). Animal studies suggest that (single-dose) allopurinol (xanthine oxidase inhibitor with high oral bioavailability and long-lasting active metabolites) may reduce this risk; human study results are conflicting. The aim of this study was to determine if allopurinol decreases the rate of PEP. METHODS Patients referred for ERCP to 9 endoscopists at 2 tertiary centers were randomized to receive either allopurinol 300 mg or identical placebo orally 60 minutes before ERCP, stratified according to high-risk ERCP (manometry or pancreatic therapy). The primary outcome (PEP) was adjudicated blindly; pancreatitis was defined according to the Cotton consensus, and evaluated at 48 hours and 30 days. Secondary outcomes included severe PEP, length of stay, and mortality (nil). The trial was terminated after the blinded (midpoint) interim analysis, as recommended by the independent data and safety monitoring committee. RESULTS We randomized 586 subjects, 293 to each arm. The crude PEP rates were 5.5% (allopurinol) and 4.1% (placebo), (P = .44; difference = 1.4%; 95% confidence interval, -2.1% to 4.8%). The Mantel-Haenszel combined risk ratio for PEP with allopurinol, considering stratification, was 1.37 (95% confidence interval, 0.65-2.86). Subgroup analyses suggested nonsignificant trends toward possible benefit in the high-risk group, and possible harm for the remaining subjects. Logistic regression found pancreatic therapy, pancreatic injection, and prior PEP to be the only independent predictors of PEP. CONCLUSIONS Allopurinol does not appear to reduce the overall risk of PEP; however, its potential benefit in the high-risk group (but potential harm for non-high-risk patients) means further study is required.
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Affiliation(s)
- Joseph Romagnuolo
- Digestive Disease Center, Department of Medicine, Medical University of South Carolina, South Carolina 29425, USA.
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Zheng M, Bai J, Yuan B, Lin F, You J, Lu M, Gong Y, Chen Y. Meta-analysis of prophylactic corticosteroid use in post-ERCP pancreatitis. BMC Gastroenterol 2008; 8:6. [PMID: 18271973 PMCID: PMC2258301 DOI: 10.1186/1471-230x-8-6] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2007] [Accepted: 02/14/2008] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography and benefit of pharmacological treatment is unclear. Although prophylactic use of corticosteroid for reduction of pancreatic injury after ERCP has been evaluated, discrepancy about beneficial effect of corticosteroid on pancreatic injury still exists. The aim of current study is to evaluate effectiveness and safety of corticosteroid in prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). METHODS We employed the method recommended by the Cochrane Collaboration to perform a meta-analysis of seven randomized controlled trials (RCTs) of corticosteroid in prevention of post-ERCP pancreatitis (PEP) around the world. RESULTS Most of the seven RCTs were of high quality. When the RCTs were analyzed, odds ratios (OR) for corticosteroid were 1.13 [95% CI (0.89~1.44), p = 0.32] for PEP, 1.61 [95% CI (0.74~3.52), p = 0.23] for severe PEP, 0.92 [95% CI (0.57~1.48), p = 0.73] for post-ERCP hyperamylasemia respectively. The results indicated that there were no beneficial effects of corticosteroid on acute pancreatitis and hyperamylasemia. No evidence of publication bias was found. CONCLUSION Corticosteroids cannot prevent pancreatic injury after ERCP. Therefore, their use in the prophylaxis of PEP is not recommended.
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Affiliation(s)
- Minghua Zheng
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
| | - Jianling Bai
- Department of Epidemiology and Biostatistics, School of Public Health Nanjing Medical University, Nanjing, China
| | - Bosi Yuan
- Department of Gastroenterology, Clinical School of Nanjing, Southern Medical University, Jinling Hospital, Nanjing, China
| | - Feng Lin
- Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
| | - Jie You
- Department of Oncology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
| | - Mingqin Lu
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
| | - Yuewen Gong
- Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada
| | - Yongping Chen
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
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Risks of Endoscopic Retrograde Cholangiopancreatography and Sphincterotomy. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2008. [DOI: 10.1016/j.tgie.2007.08.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Comert B, Isik AT, Aydin S, Bozoglu E, Unal B, Deveci S, Mas N, Cinar E, Mas MR. Combination of allopurinol and hyperbaric oxygen therapy: a new treatment in experimental acute necrotizing pancreatitis? World J Gastroenterol 2007; 13:6203-6207. [PMID: 18069760 DOI: 10.3748/wjg.13.6203] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the individual and combined effects of allopurinol and hyperbaric oxygen (HBO) therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation (BT) in the experimental rat acute pancreatitis (AP). METHODS Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls (sham, Group I). AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group II received saline, Group III allopurinol, Group IV allopurinol plus HBO and Group V HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS Serum amylase levels were lower in Groups III, IV and V compared to Group II (974 +/- 110, 384 +/- 40, 851 +/- 56, and 1664 +/- 234 U/L, respectively, P < 0.05, for all). Combining the two treatment options revealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations (13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P < 0.01). Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups III, IV and V compared to Group II (54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P < 0.05 for all). CONCLUSION The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.
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Affiliation(s)
- Bilgin Comert
- Division of Intensive Care, Departments of Internal Medicine, Gulhane School of Medicine, GATA Geriatri BD, Etlik, Ankara 06018, Turkey
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Comert B, Isik AT, Aydin S, Bozoglu E, Unal B, Deveci S, Mas N, Cinar E, Mas MR. Combination of allopurinol and hyperbaric oxygen therapy: a new treatment in experimental acute necrotizing pancreatitis? World J Gastroenterol 2007; 13:6203-6207. [PMID: 18069760 PMCID: PMC4171230 DOI: 10.3748/wjg.v13.i46.6203] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2007] [Revised: 09/16/2007] [Accepted: 10/28/2007] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the individual and combined effects of allopurinol and hyperbaric oxygen (HBO) therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation (BT) in the experimental rat acute pancreatitis (AP). METHODS Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls (sham, Group I). AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group II received saline, Group III allopurinol, Group IV allopurinol plus HBO and Group V HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS Serum amylase levels were lower in Groups III, IV and V compared to Group II (974 +/- 110, 384 +/- 40, 851 +/- 56, and 1664 +/- 234 U/L, respectively, P < 0.05, for all). Combining the two treatment options revealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations (13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P < 0.01). Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups III, IV and V compared to Group II (54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P < 0.05 for all). CONCLUSION The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.
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Cheon YK, Cho KB, Watkins JL, McHenry L, Fogel EL, Sherman S, Schmidt S, Lazzell-Pannell L, Lehman GA. Efficacy of diclofenac in the prevention of post-ERCP pancreatitis in predominantly high-risk patients: a randomized double-blind prospective trial. Gastrointest Endosc 2007; 66:1126-32. [PMID: 18061712 DOI: 10.1016/j.gie.2007.04.012] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2006] [Accepted: 04/09/2007] [Indexed: 02/08/2023]
Abstract
BACKGROUND Pancreatitis is one of the major complications of ERCP and endoscopic sphincterotomy. It has been shown that nonsteriodal anti-inflammatory drugs are potent inhibitors of phospholipase A(2), activity which is increased in pancreatitis. A previous study showed reduction of post-ERCP pancreatitis with administration of rectal diclofenac. OBJECTIVE The aim of this study was to determine whether prophylactic oral diclofenac will reduce the incidence and the severity of ERCP-induced pancreatitis, especially in high-risk patients. DESIGN Single-center, randomized, double-blinded, prospective study. SETTING Indiana University Medical Center. PATIENTS A total of 207 evaluable patients were randomized to receive either diclofenac 50 mg or placebo by mouth 30 to 90 minutes before and 4 to 6 hours after ERCP. RESULTS The groups were similar with regard to patient demographics and to patient and procedure risk factors for post-ERCP pancreatitis. The overall incidence of post-ERCP pancreatitis was 16.4%. It occurred in 17 of 102 patients in the control group (16.7%) and in 17 of 105 patients in diclofenac group (16.2%). The pancreatitis was graded mild in 9.8%, moderate in 5.9%, and severe 1.0% of the control group, and mild in 10.5%, moderate in 4.8%, and severe in 1.0% of the diclofenac group. In high-risk patients, the incidence of post-ERCP pancreatitis was 17.3%. It occurred in 18.0% (16/89) in the control group and in 17.8% (16/90) in the diclofenac group. There was no significant difference between the groups in the frequency or severity of post-ERCP pancreatitis in overall and high-risk patients; however, the power of the study was less than 45%. CONCLUSIONS Prophylactic orally administered diclofenac was not observed to affect the frequency or severity of post-ERCP pancreatitis in high-risk patients.
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Affiliation(s)
- Young Koog Cheon
- Indiana University Medical Center; Indianapolis, Indiana 46202, USA
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Lieb JG, Draganov PV. Early successes and late failures in the prevention of post endoscopic retrograde cholangiopancreatography. World J Gastroenterol 2007; 13:3567-74. [PMID: 17659706 PMCID: PMC4146795 DOI: 10.3748/wjg.v13.i26.3567] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The only way to prevent this complication is to avoid an ERCP all together. Because of the risks involved, a careful consideration should be given to the indication for ERCP and the potential risk/benefit ratio of the test. Once a decision to perform an ERCP is made, the procedure should be carried out with meticulous care by an experienced endoscopist, and with a minimum of pancreatic duct opacification. Several pharmacologic agents have been tested, but to date the most important method of reducing post ERCP pancreatitis is the placement of pancreatic stent. Pancreatic stents should be placed in all patients at high risk of this complication such as those undergoing pancreatic sphincterotomy, pancreatic duct manipulation and intervention, and patients with suspected sphincter of Oddi dysfunction. Pancreatic stents should be also considered in patients requiring precut sphincterotomy to gain biliary access.
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Affiliation(s)
- John G Lieb
- Division of Gastroenterology, Department of Internal Medicine, University of Florida, Gainesville, FL 32610- 0214, USA
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Cooper ST, Slivka A. Incidence, risk factors, and prevention of post-ERCP pancreatitis. Gastroenterol Clin North Am 2007; 36:259-76, vii-viii. [PMID: 17533078 DOI: 10.1016/j.gtc.2007.03.006] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Because of the potential risks and consequences of post-ERCP pancreatitis, considerable efforts have been made to define patient- and procedure-related factors that may be associated with an increased risk of this complication, along with determining interventions that can be done to reduce post-ERCP pancreatitis.
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Affiliation(s)
- Scott T Cooper
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Presbyterian University Hospital, 200 Lothrop Street, M Level, C Wing, Pittsburgh, PA 15213, USA
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