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1
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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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2
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Glaubitz J, Asgarbeik S, Lange R, Mazloum H, Elsheikh H, Weiss FU, Sendler M. Immune response mechanisms in acute and chronic pancreatitis: strategies for therapeutic intervention. Front Immunol 2023; 14:1279539. [PMID: 37881430 PMCID: PMC10595029 DOI: 10.3389/fimmu.2023.1279539] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 10/02/2023] [Indexed: 10/27/2023] Open
Abstract
Acute pancreatitis (AP) is one of the most common inflammatory diseases of the gastrointestinal tract and a steady rising diagnosis for inpatient hospitalization. About one in four patients, who experience an episode of AP, will develop chronic pancreatitis (CP) over time. While the initiating causes of pancreatitis can be complex, they consistently elicit an immune response that significantly determines the severity and course of the disease. Overall, AP is associated with a significant mortality rate of 1-5%, which is caused by either an excessive pro-inflammation, or a strong compensatory inhibition of bacterial defense mechanisms which lead to a severe necrotizing form of pancreatitis. At the time-point of hospitalization the already initiated immune response is the only promising common therapeutic target to treat or prevent a severe disease course. However, the complexity of the immune response requires fine-balanced therapeutic intervention which in addition is limited by the fact that a significant proportion of patients is in danger of development or progress to recurrent and chronic disease. Based on the recent literature we survey the disease-relevant immune mechanisms and evaluate appropriate and promising therapeutic targets for the treatment of acute and chronic pancreatitis.
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Affiliation(s)
| | | | | | | | | | | | - Matthias Sendler
- Department of Medicine A, University Medicine, University of Greifswald, Greifswald, Germany
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3
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Qiu M, Zhou X, Zippi M, Goyal H, Basharat Z, Jagielski M, Hong W. Comprehensive review on the pathogenesis of hypertriglyceridaemia-associated acute pancreatitis. Ann Med 2023; 55:2265939. [PMID: 37813108 PMCID: PMC10563627 DOI: 10.1080/07853890.2023.2265939] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 09/26/2023] [Indexed: 10/11/2023] Open
Abstract
It is well known, that the inflammatory process that characterizes acute pancreatitis (AP) can lead to both pancreatic damage and systemic inflammatory response syndrome (SIRS). During the last 20 years, there has been a growing incidence of episodes of acute pancreatitis associated with hypertriglyceridaemia (HTAP). This review provides an overview of triglyceride metabolism and the potential mechanisms that may contribute to developing or exacerbating HTAP. The article comprehensively discusses the various pathological roles of free fatty acid, inflammatory response mechanisms, the involvement of microcirculation, serum calcium overload, oxidative stress and the endoplasmic reticulum, genetic polymorphism, and gut microbiota, which are known to trigger or escalate this condition. Future perspectives on HTAP appear promising, with ongoing research focused on developing more specific and effective treatment strategies.
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Affiliation(s)
- Minhao Qiu
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Xiaoying Zhou
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome, Italy
| | - Hemant Goyal
- Department of Surgery, University of TX Health Sciences Center, Houston, TX, United States
| | | | - Mateusz Jagielski
- Department of General, Gastroenterological and Oncological Surgery, Nicolaus Copernicus University in Toruń, Poland
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
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4
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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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5
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Czaja AJ. Immune Inhibitory Properties and Therapeutic Prospects of Transforming Growth Factor-Beta and Interleukin 10 in Autoimmune Hepatitis. Dig Dis Sci 2022; 67:1163-1186. [PMID: 33835375 DOI: 10.1007/s10620-021-06968-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 03/22/2021] [Indexed: 12/14/2022]
Abstract
Transforming growth factor-beta and interleukin 10 have diverse immune inhibitory properties that have restored homeostatic defense mechanisms in experimental models of autoimmune disease. The goals of this review are to describe the actions of each cytokine, review their investigational use in animal models and patients, and indicate their prospects as interventions in autoimmune hepatitis. English abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed. Transforming growth factor-beta expands the natural and inducible populations of regulatory T cells, limits the proliferation of natural killer cells, suppresses the activation of naïve CD8+ T cells, decreases the production of interferon-gamma, and stimulates fibrotic repair. Interleukin 10 selectively inhibits the CD28 co-stimulatory signal for antigen recognition and impairs antigen-specific activation of uncommitted CD4+ and CD8+ T cells. It also inhibits maturation of dendritic cells, suppresses Th17 cells, supports regulatory T cells, and limits production of diverse pro-inflammatory cytokines. Contradictory immune stimulatory effects have been associated with each cytokine and may relate to the dose and accompanying cytokine milieu. Experimental findings have not translated into successful early clinical trials. The recombinant preparation of each agent in low dosage has been safe in human studies. In conclusion, transforming growth factor-beta and interleukin 10 have powerful immune inhibitory actions of potential therapeutic value in autoimmune hepatitis. The keys to their therapeutic application will be to match their predominant non-redundant function with the pivotal pathogenic mechanism or cytokine deficiency and to avoid contradictory immune stimulatory actions.
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Affiliation(s)
- Albert J Czaja
- Professor Emeritus of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street S.W., Rochester, MN, 55905, USA.
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6
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Obeidat AE, Mahfouz R, Monti G, Kozai L, Darweesh M, Mansour MM, Alqam A, Hernandez D. Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: What We Already Know. Cureus 2022; 14:e21773. [PMID: 35251843 PMCID: PMC8890589 DOI: 10.7759/cureus.21773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2022] [Indexed: 11/05/2022] Open
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7
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Watkins LR, Chavez RA, Landry R, Fry M, Green-Fulgham SM, Coulson JD, Collins SD, Glover DK, Rieger J, Forsayeth JR. Targeted interleukin-10 plasmid DNA therapy in the treatment of osteoarthritis: Toxicology and pain efficacy assessments. Brain Behav Immun 2020; 90:155-166. [PMID: 32800926 DOI: 10.1016/j.bbi.2020.08.005] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 08/02/2020] [Accepted: 08/07/2020] [Indexed: 02/02/2023] Open
Abstract
Osteoarthritis results in chronic pain and loss of function. Proinflammatory cytokines create both osteoarthritis pathology and pain. Current treatments are poorly effective, have significant side effects, and have not targeted the cytokines central to osteoarthritis development and maintenance. Interleukin-10 is an anti-inflammatory cytokine that potently and broadly suppresses proinflammatory cytokine activity. However, interleukin-10 protein has a short half-life in vivo and poor joint permeability. For sustained IL-10 activity, we developed a plasmid DNA-based therapy that expresses a long-acting human interleukin-10 variant (hIL-10var). Here, we describe the 6-month GLP toxicology study of this therapy. Intra-articular injections of hIL-10var pDNA into canine stifle joints up to 1.5 mg bilaterally were well-tolerated and without pathologic findings. This represents the first long-term toxicologic assessment of intra-articular pDNA therapy. We also report results of a small double-blind, placebo-controlled study of the effect of intra-articular hIL-10var pDNA on pain measures in companion (pet) dogs with naturally occurring osteoarthritis. This human IL-10-based targeted therapy reduced pain measures in the dogs, based on veterinary and owner ratings, without any adverse findings. These results with hIL-10var pDNA therapy, well-tolerated and without toxicologic effects, establish the basis for clinical trials of a new class of safe and effective therapies for OA.
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Affiliation(s)
- Linda R Watkins
- Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado - Boulder, Boulder, CO, USA.
| | | | - Robert Landry
- Colorado Center for Animal Pain Management Veterinary Care Center, Westminster, CO, USA
| | - Megan Fry
- Colorado Center for Animal Pain Management Veterinary Care Center, Westminster, CO, USA
| | - Suzanne M Green-Fulgham
- Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado - Boulder, Boulder, CO, USA
| | - Jonathan D Coulson
- Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado - Boulder, Boulder, CO, USA
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8
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Efficacy of Epinephrine Injection in Preventing Post-ERCP Pancreatitis. Surg Laparosc Endosc Percutan Tech 2020; 31:208-214. [PMID: 33048897 DOI: 10.1097/sle.0000000000000867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 08/14/2020] [Indexed: 11/25/2022]
Abstract
BACKGROUND Rectal indomethacin or a topical spray of epinephrine to the papilla of Vater has each shown efficacy alone in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We supposed that a submucosal epinephrine injection would be more effective and longer acting than a topical epinephrine spray and therefore would further reduce the incidence of PEP. PATIENTS AND METHODS A retrospective analysis was conducted of 412 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between January 2017 and December 2019. These patients were divided into 2 groups: the indomethacin group and the indomethacin plus the submucosal epinephrine injection group. The incidence rates and severity of PEP, post-ERCP hyperamylasemia, other outcomes, and any other adverse events were compared between the groups. RESULTS Baseline demographic and clinical characteristics and procedure-related parameters were similar between the 2 groups. The incidence of PEP was 0.4% in the epinephrine group compared with 5.1% in the indomethacin group (P<0.001). Post-ERCP hyperamylasemia occurred in 24.6% of patients in the indomethacin group, whereas 7.6% of patients in the epinephrine group developed this condition; the difference was significant (P<0.001). Postsphincterotomy bleeding occurred in 5 patients, all of whom were in the indomethacin group (P<0.001). Other adverse events, including arrhythmias, acute coronary events, stroke, or hypertension were not significantly different between the 2 groups. CONCLUSION Addition of a submucosal epinephrine injection in conjunction with rectal indomethacin significantly reduced the incidence of PEP, post-ERCP hyperamylasemia, and postsphincterotomy bleeding.
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9
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Abstract
The incidence of acute pancreatitis continues to increase worldwide, and it is one of the most common gastrointestinal causes for hospital admission in the USA. In the past decade, substantial advancements have been made in our understanding of the pathophysiological mechanisms of acute pancreatitis. Studies have elucidated mechanisms of calcium-mediated acinar cell injury and death and the importance of store-operated calcium entry channels and mitochondrial permeability transition pores. The cytoprotective role of the unfolded protein response and autophagy in preventing sustained endoplasmic reticulum stress, apoptosis and necrosis has also been characterized, as has the central role of unsaturated fatty acids in causing pancreatic organ failure. Characterization of these pathways has led to the identification of potential molecular targets for future therapeutic trials. At the patient level, two classification systems have been developed to classify the severity of acute pancreatitis into prognostically meaningful groups, and several landmark clinical trials have informed management strategies in areas of nutritional support and interventions for infected pancreatic necrosis that have resulted in important changes to acute pancreatitis management paradigms. In this Review, we provide a summary of recent advances in acute pancreatitis with a special emphasis on pathophysiological mechanisms and clinical management of the disorder.
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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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Serum interleukin-35 and pentraxin-3 levels in patients with mild acute pancreatitis. GASTROENTEROLOGY REVIEW 2019; 14:48-54. [PMID: 30944677 PMCID: PMC6444112 DOI: 10.5114/pg.2019.83425] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 10/11/2018] [Indexed: 01/21/2023]
Abstract
Introduction Interleukin-35 (IL-35) is a newly defined potent anti-inflammatory cytokine that is predominantly produced by regulatory T cells, and pentraxin-3 belongs to the acute-phase proteins. Aim To measure the serum IL-35 and pentraxin-3 levels in the early phase of mild acute pancreatitis (AP). Material and methods Eighty-three patients with mild AP and 30 healthy controls were included in the study. The serum levels of IL-35 and pentraxin-3 were measured by enzyme-linked immunosorbent assay upon admission and at the 48th hour after diagnosis. Results The mean value of serum IL-35 levels in patients with mild acute pancreatitis at admission was 5.91 ng/ml (4.21–7.90) and was significantly lower than those in healthy controls (25.53 ng/ml (12.79–54.73, p < 0.001)) and 48-hour value were (6.79 ng/ml (4.42–9.62) (p = 0.015)). The mean value of serum pentraxin-3 levels in patients at the time of admission was 6.75 ng/ml (4.42–9.62) and there was no significant difference from healthy controls, at 7.64 ng/ml (6.58–8.62, p > 0.05). Also there was no significant difference between the mean value at admission and the mean value at 48-hour, 6.75 ng/ml (4.74–9.06, p > 0.05). Conclusions Interleukin-35 can be used in diagnosis and follow-up in patients with mild AP.
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12
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Plavsic I, Zitinic I, Tulic V, Poropat G, Marusic M, Hauser G. Early immune response in post endoscopic retrograde cholangiopancreatography pancreatitis as a model for acute pancreatitis. World J Meta-Anal 2019; 7:96-100. [DOI: 10.13105/wjma.v7.i3.96] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 03/27/2019] [Accepted: 03/28/2019] [Indexed: 02/06/2023] Open
Abstract
This opinion review summarizes comparison of clinical presentation and immunology of post-endoscopic pancreatitis and acute pancreatitis (AP) of other etiology. The rationale for this topic was found in studies that mention differences in clinical presentation between these entities, stating that severe form of AP after endoscopic retrograde cholangiopancreatography was more severe than AP of other etiology. Found difference in clinical presentation may have a background in different immunology that needs to be further investigated.
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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 Zitinic
- Department of Emergency Medicine, Clinical Hospital Centre, Rijeka 51000, Croatia
| | - Vera Tulic
- Department of Anesthesiology and Critical care medicine, 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, Medical Faculty Rijeka, University of Rijeka, Rijeka 51000, Croatia
| | - Marinko Marusic
- Department of Internal Medicine, Division of Gastroenterology, Clinical Hospital Sv. Duh, Zagreb, Faculty of Health Studies, University of Rijeka, Rijeka 51000, Croatia
- Medical Faculty Osijek, University of J.J. Stossmayer, Osijek 31000, 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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13
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Bai Y, Li DF, Wang SL, Zhao SB, Ma SR, Zhang ST, Li ZS. Chinese expert consensus on perioperative medications for endoscopic retrograde cholangiopancreatography (ERCP). J Dig Dis 2019; 20:103-113. [PMID: 30604509 DOI: 10.1111/1751-2980.12699] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 12/22/2018] [Accepted: 01/02/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Yu Bai
- Department of Gastroenterology, Changhai Hospital, The Naval Medical University (Second Military Medical University), Shanghai, China
| | - De Feng Li
- Department of Gastroenterology, Shenzhen People's Hospital (Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China
| | - Shu Ling Wang
- Department of Gastroenterology, Changhai Hospital, The Naval Medical University (Second Military Medical University), Shanghai, China
| | - Sheng Bing Zhao
- Department of Gastroenterology, Changhai Hospital, The Naval Medical University (Second Military Medical University), Shanghai, China
| | - Shu Ren Ma
- Department of Gastroenterology, The General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China
| | - Shu Tian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhao Shen Li
- Department of Gastroenterology, Changhai Hospital, The Naval Medical University (Second Military Medical University), Shanghai, China
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14
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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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15
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Abstract
BACKGROUND The association between interleukin-10 (IL-10) gene rs1800896 polymorphism and susceptibility to acute pancreatitis (AP) has been investigated in several studies, but with contradictory findings. Therefore, a comprehensive meta-analysis is needed to assess the strength of such association. METHODS Literatures on PubMed, EMBASE, and CNKI were searched to identify relevant studies. The strength of association between IL-10 gene rs1800896 polymorphism and AP risk was assessed using pooled odds ratios and 95% confidence intervals. RESULTS Totally 7 case-control studies involving 1527 cases and 1511 controls were identified. Analyses proved that IL-10 gene rs1800896 polymorphism was significantly associated with an increased risk of AP. Stratification analysis of ethnicity found such significant association only among Asians, but not Caucasians. CONCLUSION IL-10 gene rs1800896 polymorphism increases the risk of AP.
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Affiliation(s)
| | - Ailing Liu
- Department of Emergency, Yi Du Central Hospital of Wei Fang, Shandong
| | - Bingzhi Zhou
- Department of Emergency, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | | | - Guangjun Jin
- Department of Emergency, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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16
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Abstract
Alcohol and gallstones are the most common etiologic factors in acute pancreatitis (AP). Recurrent AP can lead to chronic pancreatitis (CP). Although the underlying pathophysiology of the disease is complex, immune cells are critical in the pathogenesis of pancreatitis and determining disease severity. In this review, we discuss the role of innate and adaptive immune cells in both AP and CP, potential immune-based therapeutic targets, and animal models used to understand our knowledge of the disease. The relative difficulty of obtaining human pancreatic tissue during pancreatitis makes animal models necessary. Animal models of pancreatitis have been generated to understand disease pathogenesis, test therapeutic interventions, and investigate immune responses. Although current animal models do not recapitulate all aspects of human disease, until better models can be developed available models are useful in addressing key research questions. Differences between experimental and clinical pancreatitis need consideration, and when therapies are tested, models with established disease ought to be included.
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17
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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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18
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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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19
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A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis. Am J Gastroenterol 2014; 109:903-9. [PMID: 24513806 DOI: 10.1038/ajg.2014.9] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2013] [Accepted: 12/06/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Recent data suggest that indomethacin can reduce the risk of post-ERCP pancreatitis (PEP) in high-risk individuals. However, whether the combination of indomethacin and sublingual nitrates is superior to indomethacin alone is unknown. Therefore, we aimed to evaluate the efficacy of rectally administered indomethacin plus sublingual nitrate compared with indomethacin alone to prevent PEP. METHODS During a 17-month period, all eligible patients who underwent ERCP were enrolled in this study. We excluded patients who had undergone a prior endoscopic sphincterotomy. In a double-blind controlled randomized trial, patients received a suppository containing 100 mg of indomethacin, plus 5 mg of sublingual nitrate (group A), or a suppository containing 100 mg of indomethacin, plus sublingual placebo (group B), before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. RESULTS Of the 300 enrolled patients, 150 received indomethacin plus nitrate. Thirty-three patients developed pancreatitis: 10 (6.7%) in group A and 23 (15.3%) in group B (P=0.016, risk ratio=0.39, 95% confidence intervals (CI): 0.18-0.86). More than 80% of the patients were at high risk of developing pancreatitis after ERCP. Absolute risk reduction, relative risk reduction, and number needed to treat for the prevention of PEP were 8.6% (95% CI: 4.7-14.5), 56.2% (95% CI: 50.6-60.8), and 12 (95% CI: 7-22), respectively. CONCLUSIONS Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.
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20
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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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21
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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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22
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Zheng L, Xue J, Jaffee EM, Habtezion A. Role of immune cells and immune-based therapies in pancreatitis and pancreatic ductal adenocarcinoma. Gastroenterology 2013; 144:1230-40. [PMID: 23622132 PMCID: PMC3641650 DOI: 10.1053/j.gastro.2012.12.042] [Citation(s) in RCA: 250] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Revised: 12/12/2012] [Accepted: 12/21/2013] [Indexed: 12/22/2022]
Abstract
Immune cells are important in the pathogenesis of acute pancreatitis and determine disease severity. Results from cytokine-based clinical trials for acute pancreatitis have been disappointing, so strategies that target and alter the behavior of infiltrating immune cells require consideration. Recurrent acute pancreatitis can progress to chronic pancreatitis, which is a well-described risk factor for pancreatic ductal adenocarcinoma (PDA). However, most patients with chronic pancreatitis do not develop PDA, and most patients with PDA do not have a history of pancreatitis. Interestingly, chronic pancreatitis and PDA tissues have similarities in their desmoplasia and inflammatory infiltrates, indicating overlapping inflammatory responses. Further studies are needed to determine the differences and similarities of these responses, improve our understanding of PDA pathogenesis, and develop specific immune-based therapies. Immune cells in PDA produce immunosuppressive signals that allow tumors to evade the immune response. Unlike single therapeutic agent studies that block immunosuppressive mechanisms, studies of combination therapies that include therapeutic vaccines have provided promising results.
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Affiliation(s)
- Lei Zheng
- Stanford University School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, California and The Sidney Kimmel Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jing Xue
- Stanford University School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, California and The Sidney Kimmel Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Elizabeth M. Jaffee
- Stanford University School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, California and The Sidney Kimmel Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Aida Habtezion
- Stanford University School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, California and The Sidney Kimmel Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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23
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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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24
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Bexelius TS, Blomberg J, Lu YX, Håkansson HO, Möller P, Nordgren CE, Arnelo U, Lagergren J, Lindblad M. Losartan to prevent hyperenzymemia after endoscopic retrograde cholangiopan-creatography: A randomized clinical trial. World J Gastrointest Endosc 2012; 4:506-512. [PMID: 23189222 PMCID: PMC3506968 DOI: 10.4253/wjge.v4.i11.506] [Citation(s) in RCA: 4] [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] [Indexed: 02/05/2023] Open
Abstract
AIM: To study if the angiotensin II receptor blockers (ARB) losartan counteracts pancreatic hyperenzymemia as measured 24 h after endoscopic retrograde cholangiopancreatography (ERCP).
METHODS: A triple-blind and placebo-controlled randomized clinical trial was performed at two Swedish hospitals in 2006-2008. Patients over 18 years of age undergoing ERCP, excluding those with current pancreatitis, current use of ARB, and severe disease, such as sepsis, liver and renal failure. One oral dose of 50 mg losartan or placebo was given one hour before ERCP. The relative risk of hyperenzymemia 24 h after ERCP was estimated using multivariable logistic regression, and expressed as odds ratio with 95% confidence intervals (CIs), including adjustment for potential remaining confounding.
RESULTS: Among 76 participating patients, 38 were randomized to the losartan and the placebo group, respectively. The incidence rates of hyperenzymemia and acute pancreatitis among all 76 participating patients were 21% and 12%, respectively. Hyperenzymemia was detected in 9 and 7 patients in the losartan and placebo group, respectively. There were no major differences between the comparison groups regarding cannulation difficulty, findings, or proportion of patients requiring drainage of the bile ducts. There were, however, more pancreatic duct injections, a greater extent of pancreatography, and more biliary sphincterotomies in the losartan group than in the placebo group. Losartan was not associated with risk of hyperenzymemia compared to the placebo group after multi-varible logistic regression analysis (odds ratio 1.6, 95%CI 0.3-7.8).
CONCLUSION: In this randomized trial 50 mg losartan given orally had no prophylactic effect on development of hyperenzymemia after ERCP.
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Affiliation(s)
- Tomas Sjöberg Bexelius
- Tomas Sjöberg Bexelius, John Blomberg, Yun-Xia Lu, Jesper Lagergren, Mats Lindblad, Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, 176 70 Stockholm, Sweden
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25
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Sidhapuriwala JN, Hegde A, Ang AD, Zhu YZ, Bhatia M. Effects of S-propargyl-cysteine (SPRC) in caerulein-induced acute pancreatitis in mice. PLoS One 2012; 7:e32574. [PMID: 22396778 PMCID: PMC3291555 DOI: 10.1371/journal.pone.0032574] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2011] [Accepted: 01/27/2012] [Indexed: 01/23/2023] Open
Abstract
Hydrogen sulfide (H(2)S), a novel gaseous messenger, is synthesized endogenously from L-cysteine by two pyridoxal-5'-phosphate-dependent enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). S-propargyl-cysteine (SPRC) is a slow H(2)S releasing drug that provides cysteine, a substrate of CSE. The present study was aimed to investigate the effects of SPRC in an in vivo model of acute pancreatitis (AP) in mice. AP was induced in mice by hourly caerulein injections (50 µg/kg) for 10 hours. Mice were treated with SPRC (10 mg/kg) or vehicle (distilled water). SPRC was administered either 12 h before or 3 h before the induction of pancreatitis. Mice were sacrificed 1 h after the last caerulein injection. Blood, pancreas and lung tissues were collected and processed to measure the plasma amylase, plasma H(2)S, myeloperoxidase (MPO) activities and cytokine levels in pancreas and lung. The results revealed that significant reduction of inflammation, both in pancreas and lung was associated with SPRC given 3 h prior to the induction of AP. Furthermore, the beneficial effects of SPRC were associated with reduction of pancreatic and pulmonary pro-inflammatory cytokines and increase of anti-inflammatory cytokine. SPRC administered 12 h before AP induction did not cause significant improvement in pancreatic and lung inflammation. Plasma H(2)S concentration showed significant difference in H(2)S levels between control, vehicle and SPRC (administered 3 h before AP) treatment groups. In conclusion, these data provide evidence for protective effects of SPRC in AP possibly by virtue of its slow release of endogenous H(2)S.
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Affiliation(s)
| | - Akhil Hegde
- Department of Pathology, University of Otago, Christchurch, New Zealand
| | - Abel D. Ang
- Department of Pathology, University of Otago, Christchurch, New Zealand
| | - Yi Zhun Zhu
- Department of Pharmacology, National University of Singapore, Singapore, Singapore
- Department of Pharmacology, Fudan University, Shanghai, China
| | - Madhav Bhatia
- Department of Pathology, University of Otago, Christchurch, New Zealand
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26
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Mayerle J, Dummer A, Sendler M, Malla SR, van den Brandt C, Teller S, Aghdassi A, Nitsche C, Lerch MM. Differential roles of inflammatory cells in pancreatitis. J Gastroenterol Hepatol 2012; 27 Suppl 2:47-51. [PMID: 22320916 DOI: 10.1111/j.1440-1746.2011.07011.x] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The incidence of acute pancreatitis per 100,000 of population ranges from 5 to 80. Patients suffering from hemorrhagic-necrotizing pancreatitis die in 10-24% of cases. 80% of all cases of acute pancreatitis are etiologically linked to gallstone disease immoderate alcohol consumption. As of today no specific causal treatment for acute pancreatitis exists. Elevated C-reactive protein levels above 130,mg/L can also predict a severe course of acute pancreatitis. The essential medical treatment for acute pancreatitis is the correction of hypovolemia. Prophylactic antibiotics should be restricted to patients with necrotizing pancreatitis, infected necrosis or other infectious complications. However, as premature intracellular protease activation is known to be the primary event in acute pancreatitis. Severe acute pancreatitis is characterized by an early inflammatory immune response syndrome (SIRS) and a subsequent compensatory anti-inflammatory response syndrome (CARS) contributing to severity as much as protease activation does. CARS suppresses the immune system and facilitates nosocomial infections including infected pancreatic necrosis, one of the most feared complications of the disease. A number of attempts have been made to suppress the early systemic inflammatory response but even if these mechanisms have been found to be beneficial in animal models they failed in daily clinical practice.
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Affiliation(s)
- Julia Mayerle
- Department of Medicine A, University Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany.
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27
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Is high-dose nafamostat mesilate effective for the prevention of post-ERCP pancreatitis, especially in high-risk patients? Pancreas 2011; 40:1215-9. [PMID: 21775918 DOI: 10.1097/mpa.0b013e31822116d5] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Infusion of the protease inhibitor nafamostat mesilate (20 mg) effectively prevents post-ERCP pancreatitis, but only in low-risk groups. This study was performed to evaluate the use of high-dose nafamostat mesilate (50 mg) for prevention of post-ERCP pancreatitis (PEP), especially in high-risk groups. METHODS A total of 608 patients who underwent ERCP were included; 13 patients were excluded. Patients were divided into 3 groups: controls (group A), infusion with 20 mg of nafamostat mesilate (group B), or infusion with 50 mg of nafamostat mesilate (group C). The incidence of PEP was analyzed. RESULTS The overall incidence of acute pancreatitis was 7.4% (44/595). There was a significant difference in the incidence of PEP with or without nafamostat mesilate (13.0% vs 4.0% and 5.1%, respectively; P < 0.0001). Subgroup analysis showed that in low-risk patients, the rate of PEP was significantly different with nafamostat (11.9% vs 2.7% and 4.0%, respectively; P = 0.007). In high-risk patients, the rate of PEP was not significantly different among treatment groups (14.6% vs 5.9% vs 6.9%, respectively; P = 0.108). CONCLUSIONS Nafamostat mesilate prophylaxis (20 or 50 mg) is effective in preventing post-ERCP pancreatitis. However, the preventive effect of high-dose nafamostat mesilate (50 mg) is not significant in high-risk patients.
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Carvalho KMMB, Morais TC, de Melo TS, de Castro Brito GA, de Andrade GM, Rao VS, Santos FA. The natural flavonoid quercetin ameliorates cerulein-induced acute pancreatitis in mice. Biol Pharm Bull 2011; 33:1534-9. [PMID: 20823570 DOI: 10.1248/bpb.33.1534] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Many plant-derived flavonoids including quercetin exhibit antioxidant and antiinflammatory properties. Proinflammatory cytokines and oxidative stress play an important role in acute pancreatitis. This study aimed to evaluate the effect of quercetin on cerulein-induced acute pancreatitis in mice. Animal groups were pretreated with quercetin (25, 50, 100 mg/kg, per os (p.o.)), thalidomide (200 mg/kg, p.o.) or vehicle (2% dimethyl sulfoxide (DMSO)) 1 h before hourly (x5) intraperitoneal injections of cerulein. A saline (0.9%, NaCl)-treated control group was included for comparison. Cerulein significantly enhanced the serum levels of amylase and lipase, and pancreatic myeloperoxidase activities, malondialdehyde and the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6, as well as the pancreatic wet weight/body weight ratio. Cerulein significantly reduced the serum levels of IL-10. Histological assessment of the pancreas showed tissue edema, neutrophil infiltration, acinar vacuolization, and cell necrosis and a marked increase in the immunoreactivity staining for TNF-alpha. Pretreatment with quercetin or thalidomide significantly attenuated the severity of cerulein-induced acute pancreatitis as evidenced by effective reductions in the pancreatic wet weight/body weight ratio, biochemical indices, proinflammatory cytokines, myeloperoxidase activity, malondialdehyde formation, and an increase in antiinflammatory cytokine IL-10. Quercetin treatment also markedly suppressed the histological changes such as pancreatic edema, inflammatory cell infiltration, acinar cell necrosis, and the expression of TNF-alpha. Taken together, these results indicate that quercetin ameliorates the severity of cerulein-induced acute pancreatitis by acting as an antiinflammatory and antioxidant agent.
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29
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Xu LH, Qian JB, Gu LG, Qiu JW, Ge ZM, Lu F, Wang YM, Li YM, Lu HS. Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis by epinephrine sprayed on the papilla. J Gastroenterol Hepatol 2011; 26:1139-44. [PMID: 21392105 DOI: 10.1111/j.1440-1746.2011.06718.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Epinephrine sprayed on the papilla may reduce papillary edema and prevent acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to evaluate the effects of localized irrigation with epinephrine saline for prevention of post-ERCP pancreatitis (PEP). METHODS A total of 941 patients who were scheduled for ERCP were recruited into this study. We randomized the patients to have 20 mL of either 0.02% epinephrine or saline sprayed on the papilla after diagnostic ERCP to prevent post-ERCP pancreatitis. We recorded duct visualization, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. The serum amylase levels were measured at 6, 24 and 48 h after ERCP. We counted the patients of PEPs and compared whether there was significant difference between the pancreatitis group and the no pancreatitis group. RESULTS A univariate analysis of the explanatory variables between the epinephrine and control groups, the pancreatitis and no pancreatitis groups revealed the treatment to be effective, but most of the groups were not statistically significant. PEPs occurred in 40 of the 941 patients (4.25%), the incidence of pancreatitis tended to be higher in the control group (31/480, 6.45%) than in the epinephrine group (9/461, 1.95%) (P = 0.0086). CONCLUSIONS Epinephrine sprayed on the papilla may be effective to prevent PEP. Female patients (aged ≥ 18 years and < 35 years) (7/40, 17.5%), common bile duct diameter < 10 mm (27/40, 67.5%), previous cholangitis (3/40, 7.5%), body mass index ≥ 24 (22/40, 55%), and/or serum triglycerides ≥ 5.65 mmol/L (6/40, 15%), might be risk factors for post-ERCP pancreatitis, but are not statistically significant in the study.
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Affiliation(s)
- Li Hua Xu
- Department of Gastroenterology, The First People's Hospital of Nantong, Jiangsu, China.
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Cerulein-induced acute pancreatitis in PACAP knockout mice. J Mol Neurosci 2010; 43:8-15. [PMID: 20567937 DOI: 10.1007/s12031-010-9396-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2010] [Accepted: 05/23/2010] [Indexed: 12/30/2022]
Abstract
In our previous study, we reported that cerulein-induced acute pancreatitis is aggravated in pancreatic β-cell-specific pituitary adenylate cyclase-activating polypeptide (PACAP) transgenic mice, showing that an increase in pancreatic PACAP is a risk factor for progression of acute pancreatitis. Accordingly, in this study, we examined the progression of cerulein-induced acute pancreatitis in PACAP knockout (KO) mice. Unexpectedly, after cerulein, about 60% of the KO mice showed severe hypothermia below 30°C by 12 h and most of them died within 72 h. In contrast, the remaining KO and wild-type mice showed normothermia with no mortality. Thus, KO mice could be classified into two groups as hypothermic (HT-KO) and normothermic (NT-KO) to cerulein. Only HT-KO mice subsequently showed severe mortality, although both HT-KO and NT-KO mice exhibited similar susceptibility of lungs to cerulein toxicity, comparable to that in wild-type mice. Regarding pancreatitis, HT-KO mice showed ameliorated pancreatic damage without any rise in serum enzyme activities, whereas NT-KO mice exhibited a similar degree of pancreatitis to wild-type mice. Taken together, the present results indicate that lack of pancreatic PACAP did not aggravate, but rather ameliorated, cerulein-induced pancreatitis. In addition, about half of KO mice showed a novel phenotype in which cerulein caused rapid and severe hypothermia, followed by death.
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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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Pezzilli R, Morselli-Labate AM, Corinaldesi R. NSAIDs and Acute Pancreatitis: A Systematic Review. Pharmaceuticals (Basel) 2010; 3:558-571. [PMID: 27713268 PMCID: PMC4033969 DOI: 10.3390/ph3030558] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2010] [Revised: 02/11/2010] [Accepted: 03/09/2010] [Indexed: 12/14/2022] Open
Abstract
The resulting pain is the main symptom of acute pancreatitis and it should be alleviated as soon as possible. NSAIDs are the first line therapy for pain and they are generally administered to acute pancreatitis patients upon admission to the hospital. In addition, these drugs have also been used to prevent post-endoscopic cholangiopancreatography (ERCP) acute pancreatitis. On the other hand, there are several reports indicating that NSAIDs may be the actual cause of acute pancreatitis. We carried out a literature search on PubMed/MEDLINE; all full text papers published in from January 1966 to November 2009 on the use of NSAIDs in acute pancreatitis were collected; the literature search was also supplemented by a review of the bibliographies of the papers evaluated. Thus, in this article, we will systematically review the current literature in order to better illustrate the role of NSAIDs in acute pancreatitis, in particular: i) NSAIDs as a cause of acute pancreatitis; ii) their use to prevent post-retrograde ERCP pancreatitis and iii) their efficacy for pain relief in the acute illness of the pancreas.
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Affiliation(s)
- Raffaele Pezzilli
- Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
| | - Antonio Maria Morselli-Labate
- Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
| | - Roberto Corinaldesi
- Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
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Jaworek J, Leja-Szpak A, Dembiński A, Tomaszewska R, Szklarczyk J, Kot M, Nawrot-Porabka K, Bonior J, Warzecha Z, Pawlik WW. Involvement of sensory nerves in the protective effect of growth hormone on acute pancreatitis. Growth Horm IGF Res 2009; 19:517-522. [PMID: 19615927 DOI: 10.1016/j.ghir.2009.06.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2009] [Revised: 05/20/2009] [Accepted: 06/02/2009] [Indexed: 12/21/2022]
Abstract
UNLABELLED Growth hormone (GH) has been shown to protect the intestinal barrier integrity and to stimulate the production of insulin-like growth factor 1 (IGF-1), which inhibits the development of acute pancreatitis. Sensory nerves are implicated in the protection of pancreatic tissue against acute inflammation. The aim of this study was to investigate the influence of exogenous GH on acute pancreatitis (AP) and to assess the involvement of sensory nerves and IGF-1 in above effect. Studies were performed on Wistar rats. AP was induced by subcutaneous administration of caerulein (25mug/kg) to the conscious animals. GH (1 or 2mg/kg) was administered to the rats as an intraperitoneal injection 30min prior to the start of AP. To deactivate sensory nerves capsaicin was given at total dose of 100mg/kg 10days before the experiments. AP was confirmed by histological examination and manifested by the significant rises of pancreatic weight, and serum activities of lipase, TNFalpha and IL-10 (by 550%, 300% and 50%, respectively), whereas IGF-1 blood concentration was markedly reduced. Administration of GH prior to the caerulein infusion significantly increased GH, IGF-1 and IL-10 blood levels, attenuated harmful effects of AP and reduced histological manifestations of pancreatitis in the rats with intact sensory nerves. This was accompanied by the reduction of serum lipase, and TNFalpha activities. In the AP rats with capsaicin-deactivated sensory nerves GH failed to protect the pancreas against acute damage and, as a consequence of above deactivation, IGF-1 was low. CONCLUSION GH modulates the development of acute pancreatitis in the presence of active sensory nerves probably via stimulation of IGF-1 release.
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Affiliation(s)
- Jolanta Jaworek
- Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine Cracow, Poland.
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Hamagami KI, Sakurai Y, Shintani N, Higuchi N, Ikeda K, Hashimoto H, Suzuki A, Kiyama H, Baba A. Over-expression of pancreatic pituitary adenylate cyclase-activating polypeptide (PACAP) aggravates cerulein-induced acute pancreatitis in mice. J Pharmacol Sci 2009; 110:451-8. [PMID: 19672038 DOI: 10.1254/jphs.09119fp] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Development of human chronic pancreatitis is associated with intrapancreatic accumulation of pituitary adenylate cyclase-activating polypeptide (PACAP) accompanied with an altered inflammatory response (Michalski et al., Am J Physiol Gastrointest Liver Physiol. 2008;294:G50-G57). To investigate the role of pancreatic PACAP in the development of acute pancreatitis, we employed transgenic mice over-expressing PACAP in pancreatic beta-cells (PACAP-Tg). In comparison to wild-type mice, PACAP-Tg mice exhibited more severe pathophysiological signs of the cerulein-induced pancreatitis at 12 h, as evidenced by higher serum amylase and lipase levels accompanied by the exacerbation of pancreatic edema, necrosis, and inflammation. Cerulein treatment increased mRNA expression of several proinflammatory cytokines (TNFalpha, IL-1beta, and IL-6) at 12 h with similar magnitude both in wild-type and PACAP-Tg mice. In addition, the mRNA and protein levels of regenerating gene III beta (RegIIIbeta), a key factor in the pancreatic response to acute pancreatitis, were up-regulated at 24 h in wild-type mice upon cerulein administration, whereas they were attenuated in PACAP-Tg mice. These data indicate that over-expressed PACAP in pancreas enhances the cerulein-induced inflammatory response of both acinar cells, leading to aggravated acute pancreatitis, which was accompanied by a down-regulation of RegIIIbeta, an anti-inflammatory factor.
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Affiliation(s)
- Ken-ichi Hamagami
- Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, Japan
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35
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Zheng MH, Meng MB, Gu DN, Zhang L, Wu AM, Jiang Q, Chen YP. Effectiveness and tolerability of NSAIDs in the prophylaxis of pancreatitis after endoscopic retrograde cholangiopancreatography: A systematic review and meta-analysis. CURRENT THERAPEUTIC RESEARCH 2009; 70:323-334. [PMID: 24683241 PMCID: PMC3967274 DOI: 10.1016/j.curtheres.2009.08.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/29/2009] [Indexed: 02/05/2023]
Abstract
BACKGROUND Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). The beneficial effects of pharmaco-logic treatment of acute pancreatitis are unclear. Although the prophylactic use of NSAIDs for the reduction of the risk for pancreatic injury after ERCP has been assessed, the beneficial effects of NSAIDs on pancreatic injury are still being debated. OBJECTIVE The aim of this study was to determine the effectiveness and tolerability of NSAIDs in the prophylaxis of post-ERCP pancreatitis (PEP). METHODS MEDLINE (January 1966-January 2009), EMBASE (January 1966-January 2009), and the Cochrane Central Register of Controlled Trials (Issue 1, 2009) were searched using the key terms: pancreatitis, post-ERCP pancreatitis, nonsteroidal anti-inflammatory drugs, indomethacin, and diclofenac. The methods recommended by the Cochrane Collaboration and the Quality of Reporting Meta-Analyses guideline were used to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) of NSAIDs in the prevention of PEP. RESULTS Four multinational RCTs were included in the meta-analysis (969 patients). The pooled odds ratio for NSAIDs for mild PEP was 0.69 (95% CI, 0.40-1.17; P = NS); moderate to severe PEP, 0.22 (95% CI, 0.05-1.01; P = 0.05); PEP (pooled), 0.44 (95% CI, 0.21-0.93; P = 0.03); in high-risk patients, 0.49 (95% CI, 0.17-1.39; P = NS); and in low-risk patients, 0.29 (95% CI, 0.12-0.71; P = 0.006). No evidence of publication bias was found. CONCLUSION Based on the findings from the present systematic review of 4 RCTs, NSAIDs were effective and well tolerated in the prevention of PEP, especially in low-risk patients.
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Affiliation(s)
- Ming-Hua Zheng
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
| | - Mao-Bin Meng
- Division of Thoracic Oncology, Cancer Center, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China
| | - Dian-Na Gu
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
| | - Lei Zhang
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
| | - Ai-Min Wu
- Information Service Department, Library of Wenzhou Medical College, Wenzhou, China
| | - Qian Jiang
- Department of Clinical Pharmacy, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Yong-Ping Chen
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
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Muddana V, Whitcomb DC, Papachristou GI. Current management and novel insights in acute pancreatitis. Expert Rev Gastroenterol Hepatol 2009; 3:435-44. [PMID: 19673630 DOI: 10.1586/egh.09.27] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Acute pancreatitis (AP) is a common and potentially lethal acute inflammatory process. Approximately 10-20% of patients develop a severe course and suffer systemic inflammatory response and/or pancreatic necrosis (PNec). To date, there is no single biomarker proven to perform better than clinical judgment in predicting severe AP. The available prognostic clinical scoring systems are used primarily for research purposes. Management of AP is limited to supportive care and treatment of complications when they develop. Patients with mild AP require regular ward admission, fluid administration, bowel rest and pain management. Patients with signs of severe AP should be identified early and admitted promptly to an intensive-care unit. Nutrition support via nasojejunal feedings should be initiated. Sterile PNec is managed conservatively. Infected PNec requires minimally invasive debridement via endoscopic or surgical approaches. The lack of scientific advancements in the management of AP reflects the limited understanding of the early pathogenetic mechanisms and our moderate-to-poor ability to predict severe course at the time of admission.
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Affiliation(s)
- Venkata Muddana
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, PA 15219, USA
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Nøjgaard C, Hornum M, Elkjaer M, Hjalmarsson C, Heyries L, Hauge T, Bakkevold K, Andersen PK, Matzen P. Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized, double-blind, placebo-controlled multicenter trial. Gastrointest Endosc 2009; 69:e31-7. [PMID: 19410035 DOI: 10.1016/j.gie.2008.11.042] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2008] [Accepted: 11/20/2008] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Acute pancreatitis is the most dreaded complication of ERCP. Two studies have shown a significant effect of glyceryl nitrate (GN) in preventing post-ERCP pancreatitis (PEP). We wanted to evaluate this promising effect in a larger study with a realistically precalculated incidence of PEP. DESIGN/PATIENTS A randomized, double-blind, placebo-controlled multicenter study including patients from 14 European centers was performed. A total of 820 patients were entered; 806 were randomized. INTERVENTION The active drug was transdermal GN (Discotrine/Minitran, 3M Pharma) 15 mg/24 hours; placebo (PL) was an identical-looking patch applied before ERCP. A total of 401 patients received GN; 405 received PL. RESULTS Forty-seven patients had PEP (5.8%), 18 (4.5%) in the GN group and 29 (7.1%) in the PL group. The relative risk reduction of PEP in the GN group of 36% (95% CI, 11%-65%) compared with the PL group was not statistically significant (P = .11). Thirteen had mild pancreatitis (4 in the GN group, 9 in the PL group), 26 had moderate pancreatitis (9 in the GN group, 17 in the PL group), and 8 had severe pancreatitis (5 in the GN group, 3 in the PL group). Headache (P < .001) and hypotension (P = .006) were more common in the GN group. Significant variables predictive of PEP were not having biliary stones extracted; hypotension after ERCP; morphine, propofol, glucagon, and general anesthesia during the procedure; or no sufentanil during the procedure. CONCLUSIONS The trial showed no statistically significant preventive effect of GN on PEP. Because of a considerable risk of a type II error, an effect of GN may have been overlooked. (ClinicalTrials.gov ID: NCT00121901.).
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Affiliation(s)
- Camilla Nøjgaard
- Department of Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark
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Randomized study of the effect of pentoxifylline or octreotide on serum levels of TNF-alpha and IL-6 after endoscopic retrograde cholangiopancreatography. Eur J Gastroenterol Hepatol 2009; 21:529-33. [PMID: 19373973 DOI: 10.1097/meg.0b013e32831ac93a] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To study the effect of pentoxifylline and octreotide administration on serum levels of TNF-alpha and IL-6, in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), whether they developed pancreatitis or not. METHODS Out of 590 patients undergoing ERCP, 30 who developed pancreatitis and 25 who did not (controls) were enrolled. Pentoxifylline was given to 23 patients (15 with and eight without pancreatitis) and octreotide to 19 patients (nine with and 10 without pancreatitis, respectively). Thirteen patients did not receive any preventive medication (six with and seven without pancreatitis, respectively). Blood samples were collected at baseline, 6 and 24 h after ERCP. RESULTS IL-6 increased significantly in patients with pancreatitis at the 6 h (4.2 pg/ml SD: 5.8) and at the 24 h (6.6 pg/ml SD: 9.8) compared with patients without pancreatitis at the 6 h (2.1 pg/ml SD: 3.6) and 24 h (1.9 pg/ml SD: 2.5) (P < 0.01). No significant difference in the values of TNF-alpha and IL-6 obtained among the three study groups in patients with or without pancreatitis was observed. TNF-alpha levels at the 24 h were lower than baseline in patients with pancreatitis who received octreotide (P = 0.04). CONCLUSION IL-6 increased in the first 24 h of post-ERCP pancreatitis. Pentoxifylline and octreotide cannot prevent IL-6 elevation but octreotide reduces TNF-alpha levels, which may have an impact on the severity of post-ERCP pancreatitis.
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Sherman S, Cheng CL, Costamagna G, Binmoeller KF, Puespoek A, Aithal GP, Kozarek RA, Chen YK, Van Steenbergen W, Tenner S, Freeman M, Monroe P, Geffner M, Deviere J. Efficacy of recombinant human interleukin-10 in prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in subjects with increased risk. Pancreas 2009; 38:267-274. [PMID: 19214137 DOI: 10.1097/mpa.0b013e31819777d5] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Pancreatitis is the most common major complication of endoscopic retrograde cholangiopancreatography (ERCP). Inflammatory cytokines are released during acute pancreatitis. Interleukin-10 (IL-10) is a potent inhibitor of cytokines and has been shown to attenuate pancreatitis in animal models and pilot human studies. This study aimed to determine whether prophylactic IL-10 administration reduces the frequency and/or severity of post-ERCP pancreatitis in high-risk patients. METHODS A randomized, multicenter, double-blind, placebo-controlled study was conducted. Patients received IL-10 at a dose of either 8 or 20 microg/kg or placebo as a single intravenous injection 15 to 30 minutes before ERCP. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis. RESULTS A total of 305 of the planned total enrollment of 948 patients were randomized. There was a 15%, 22%, and 14% incidence of post-ERCP pancreatitis in the IL-10 (8 microg/kg), IL-10 (20 microg/kg), and placebo treatment groups, respectively (P = 0.83 for IL-10 8 microg/kg vs placebo and 0.14 for IL-10 20 microg/kg vs placebo). Due to apparent lack of efficacy, the study was terminated at an interim analysis. CONCLUSIONS : There was no apparent benefit of IL-10 treatment when compared with placebo in reducing the incidence of post-ERCP acute pancreatitis in subjects with increased risk.
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Affiliation(s)
- Stuart Sherman
- Division of Gastroenterology/Hepatology, Indiana University Medical Center, Indianapolis, IN 46202, USA.
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Choi CW, Kang DH, Kim GH, Eum JS, Lee SM, Song GA, Kim DU, Kim ID, Cho M. Nafamostat mesylate in the prevention of post-ERCP pancreatitis and risk factors for post-ERCP pancreatitis. Gastrointest Endosc 2009; 69:e11-e18. [PMID: 19327467 DOI: 10.1016/j.gie.2008.10.046] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2008] [Accepted: 10/22/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND Pancreatitis is a major complication of ERCP. OBJECTIVE To determine whether nafamostat mesylate prophylaxis decreases the incidence of post-ERCP pancreatitis (PEP). DESIGN A single-center, randomized, double-blinded, controlled trial. SETTING A large tertiary-referral center. PATIENTS From January 2005 to December 2007, a total of 704 patients who underwent ERCP were analyzed. INTERVENTION Patients received continuous infusion of 500 mL of 5% dextrose solution with 20 mg of nafamostat mesylate (354 patients) or without 20 mg of nafamostat mesylate (350 patients). Serum amylase and lipase levels were checked before ERCP, 4 and 24 hours after ERCP, and when clinically indicated. MAIN OUTCOME MEASUREMENTS The incidence of PEP and risk factors associated with the development of PEP. RESULTS The incidence of acute pancreatitis was 5.4%. There was a significant difference in the incidence of PEP between the nafamostat mesylate and control groups (3.3% vs 7.4%, respectively; P = .018). Univariate analysis identified history of acute pancreatitis (P < .001), difficult cannulation (P = .023), periampullary diverticulum (P = .004), age younger than 40 years (P = .009), and >/=5 pancreatic-duct contrast injections (odds ratio [OR] 2.736, P = .012) as statistically significant risk factors. LIMITATIONS A single-center study. CONCLUSIONS Nafamostat mesylate prophylaxis is partially effective in preventing post-ERCP pancreatitis. Independent risk factors for PEP are a history of acute pancreatitis and multiple pancreatic-duct contrast injections.
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Affiliation(s)
- Cheol Woong Choi
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
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Matsushita M, Takakuwa H, Shimeno N, Uchida K, Nishio A, Okazaki K. Epinephrine sprayed on the papilla for prevention of post-ERCP pancreatitis. J Gastroenterol 2009; 44:71-5. [PMID: 19159075 DOI: 10.1007/s00535-008-2272-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2007] [Accepted: 08/07/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND Epinephrine sprayed on the papilla may reduce papillary edema and thus prevent acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to determine the efficacy of this technique for prevention of post- ERCP pancreatitis. METHODS Patients scheduled for ERCP were recruited into this study. We randomized the patients to have 10 ml of either 0.02% epinephrine (epinephrine group) or saline (control group) sprayed on the papilla after diagnostic ERCP and prospectively analyzed the occurrence of post-ERCP pancreatitis between the groups. We recorded duct visualization, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. RESULTS There was no significant difference between the groups with regard to visualization of the bile duct and/or the main and accessory pancreatic ducts, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. Overall, post-ERCP pancreatitis occurred in 4 of the 370 patients (1.1%). The incidence of pancreatitis tended to be higher in the control group (4/185) than in the epinephrine group (0/185) (P = 0.1230). CONCLUSIONS Epinephrine sprayed on the papilla tended to prevent post-ERCP pancreatitis, although it was not statistically significant because of the low incidence of pancreatitis. Further studies on the efficacy of this technique in patients at high risk for pancreatitis, and on other volumes and/or concentrations of epinephrine, are warranted.
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Affiliation(s)
- Mitsunobu Matsushita
- Third Department of Internal Medicine, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, 573-1191, Japan
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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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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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Zhang JX, Yin JT, Cui L, Dang SC. Dynamic Changes of Soluble Fas and IL-2/IL-10 in serum and Fas Expression in Lung in the Rats of Acute Necrotizing Pancreatitis. Gastroenterology Res 2008; 1:49-54. [PMID: 27994707 PMCID: PMC5154216 DOI: 10.4021/gr2008.11.1238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2008] [Accepted: 10/29/2008] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND To investigate the dynamic changes of serum IL-2, IL-10, sFas and IL-2/IL-10 in a rat model with acute necrotizing pancreatitis (ANP). To explore the role of Th1/Th2 polarization and the Fas expression in the lung of rats with ANP. METHODS A total of 64 Sprague-Dawley rats were randomly divided into normal control group and ANP model group. ANP models were induced by injection of 50 g/L sodium taurocholate (4 mL/kg) under the pancreatic membrane. In the normal control group, the rats received isovolumetric injection of 9 g/L normal saline solution. The blood samples in each group were obtained via superior mesenteric vein for measuring IL-2, IL-10 and soluble Fas. The levels of IL-2, IL-10 and soluble Fas were determined by ELISA. The severity of lung injury was evaluated by pathologic score. The expression of Fas in lung was measured by immunohistochemistry. RESULTS In the ANP model group, levels of serum IL-2 were significantly higher than those of control group (P < 0.01), and peaked at 6 hours; levels of serum IL-10 were significantly higher than those of control group at 6 and 12 hours (P < 0.01); the ratios of IL-2/IL-10 were significantly higher than those of control group at 0.5 hours and 2 hours, however, they were significantly lower than those of control group at 6 hours, (P < 0.01), and returned to the normal level (P > 0.05). In Fas/APO-1 assay, there was no significant difference between the two groups. The pathological changes were aggravated significantly in model group compared with the control group. Immunohistochemistry stain showed Fas expression was absent in normal pulmonary tissue, whereas in pulmonary tissue Fas expression gradually increased 0.5 hours after induction of pancreatitis, and reached their peaks at 12 hours. CONCLUSIONS Fas are involved in the pathogenesis of pancreatitis associated lung injury, the mechanism might be related to the Fas mediated T helper cell apoptosis.
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Affiliation(s)
- Jian Xin Zhang
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Jiang Tao Yin
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Lei Cui
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Sheng Chun Dang
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
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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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Do the changes in the serum levels of IL-2, IL-4, TNFalpha, and IL-6 reflect the inflammatory activity in the patients with post-ERCP pancreatitis? Clin Dev Immunol 2008; 2008:481560. [PMID: 18670651 PMCID: PMC2486352 DOI: 10.1155/2008/481560] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2007] [Revised: 03/25/2008] [Accepted: 06/02/2008] [Indexed: 12/18/2022]
Abstract
BACKGROUND Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP) procedure and there are some reports showing cytokine changes in ERCP-induced pancreatits. GOALS To investigate the association between early changes (within 24 hours) in the serum interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)alpha, and IL-6 levels and the development of post-ERCP pancreatitis. STUDY Forty five consecutive patients who underwent therapeutic ERCP and 10 patients with acute pancreatitis without ERCP were enrolled to the study. Serum concentrations of IL-2, IL-4, TNFalpha, and IL-6 were determined immediately before, 12 hours and 24 hours after ERCP. RESULTS Seven of the 45 patients (15.5%) developed post-ERCP pancreatitis. The levels of IL-4 at 24 hours after ERCP were significantly lower in the patients with post-ERCP pancreatitis than in those without pancreatitis, while TNFalpha levels at 12 hours after ERCP were higher in the complicated group than those of the uncomplicated group. The ratios of TNFalpha/IL-4 at 12 and 24 hours after ERCP were found significantly higher in the patients with post-ERCP pancreatitis than in those without pancreatitis. IL-6 in the complicated patients was found significantly increased at 24 hours after ERCP. CONCLUSIONS The enhancement of serum TNFalpha and IL-6 levels in the patients with ERCP-induced pancreatitis reflects the inflammatory activity. Additionally, these cytokines together with IL-4 can be used in clinical laboratory monitoring of ERCP.
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Pre-ERCP infusion of semapimod, a mitogen-activated protein kinases inhibitor, lowers post-ERCP hyperamylasemia but not pancreatitis incidence. Gastrointest Endosc 2008; 68:246-54. [PMID: 18455169 DOI: 10.1016/j.gie.2008.01.034] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2007] [Accepted: 01/22/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND Acute pancreatitis and hyperamylasemia are frequent complications of an ERCP. Semapimod is a synthetic guanylhydrazone that inhibits the mitogen-activated protein kinase (MAPK) pathway, macrophage activation, and the production of several inflammatory cytokines. OBJECTIVE This study evaluated whether intravenous (IV) administration of semapimod given before an ERCP reduces the incidence of post-ERCP hyperamylasemia and pancreatitis. DESIGN A single-center, randomized, double-blinded, controlled trial. SETTING An academic medical center. PATIENTS Between 2001 and 2005, 242 patients who were undergoing a therapeutic ERCP at our institution were included. INTERVENTION Patients received a single IV dose of semapimod or a placebo before an ERCP. MAIN OUTCOME MEASUREMENTS The occurrence of post-ERCP pancreatitis, as well as post-ERCP hyperamylasemia. RESULTS The incidence of hyperamylasemia was significantly reduced (29.8% vs 18.4%; P = .031). Moreover, semapimod administration significantly lowered the levels of amylase during the first 24 hours after the ERCP. The incidence of clinical pancreatitis was reduced by 40%, without reaching statistical significance (14.9 vs 9.1%; P = .117). LIMITATIONS A relatively small single-center study. One dose of semapimod was used. CONCLUSIONS A single dose of IV semapimod 1 hour before an ERCP is safe and exerts a biological effect, demonstrated by a statistically significant reduction of the incidence of hyperamylasemia and the levels of post-ERCP amylase. A protective effect for the development of post-ERCP pancreatitis could not be convincingly demonstrated.
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Khoshbaten M, Khorram H, Madad L, Ehsani Ardakani MJ, Farzin H, Zali MR. Role of diclofenac in reducing post-endoscopic retrograde cholangiopancreatography pancreatitis. J Gastroenterol Hepatol 2008; 23:e11-6. [PMID: 17683501 DOI: 10.1111/j.1440-1746.2007.05096.x] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Acute pancreatitis following endoscopic retrograde cholangiography presents a unique opportunity for prophylaxis and early modification of the disease process because the initial triggering event is temporally well defined and takes place in the hospital. We report a prospective, single-center, randomized, double-blind controlled trial to determine if rectal diclofenac reduces the incidence of pancreatitis following cholangiopancreatography. METHODS Entry to the trial was restricted to patients who underwent endoscopic retrograde pancreatography. Immediately after endoscopy, patients were given a suppository containing either 100 mg diclofenac or placebo. Estimation of serum amylase level and clinical evaluation were performed in all patients. RESULTS One hundred patients entered the trial, and 50 received rectal diclofenac. Fifteen patients developed pancreatitis (15%), of whom two received rectal diclofenac and 13 received placebo (P < 0.01). CONCLUSIONS This trial shows that rectal diclofenac given immediately after endoscopic retrograde cholangiopancreatography can reduce the incidence of acute pancreatitis.
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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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Dang SC, Zhang JX, Qu JG, Mao ZF, Wang XQ, Zhu B. Dynamic changes of IL-2/IL-10, sFas and expression of Fas in intestinal mucosa in rats with acute necrotizing pancreatitis. World J Gastroenterol 2008; 14:2246-50. [PMID: 18407603 PMCID: PMC2703854 DOI: 10.3748/wjg.14.2246] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatitis (ANP).
METHODS: A total of 64 Sprague-Dawley (SD) rats were randomly divided into two groups: normal control group (C group), ANP group (P group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane. Normal control group received isovolumetric injection of 9 g/L physiological saline solution using the same method. The blood samples of the rats in each group were obtained via superior mesenteric vein to measure levels of IL-2, IL-10, sFas and calculate the value of IL-2/IL-10. The levels of IL-2, IL-10 and sFas were determined by ELISA. The severity of intestinal mucosal injury was evaluated by pathologic score. The expression of Fas in intestinal mucosal tissue was determined by immunohistochemistry staining.
RESULTS: Levels of serum IL-2 were significantly higher in P group than those of C group (2.79 ± 0.51 vs 3.53 ± 0.62, 2.93 ± 0.89 vs 4.35 ± 1.11, 4.81 ± 1.23 vs 6.94 ± 1.55 and 3.41 ± 0.72 vs 4.80 ± 1.10, respectively, P < 0.01, for all) and its reached peak at 6 h. Levels of serum IL-10 were significantly higher in P group than those of C group at 6 h and 12 h (54.61 ± 15.81 vs 47.34 ± 14.62, 141.15 ± 40.21 vs 156.12 ± 43.10, 89.18 ± 32.52 vs 494.98 ± 11.23 and 77.15 ± 22.60 vs 93.28 ± 25.81, respectively, P < 0.01, for all). The values of IL-2/IL-10 were higher significantly in P group than those of C group at 0.5 h and 2 h (0.05 ± 0.01 vs 0.07 ± 0.02 and 0.02 ± 0.01 vs 0.03 ± 0.01, respectively, P < 0.01, for all), and it were significantly lower than those of C group at 6 h (0.05 ± 0.02 vs 0.01 ± 0.01, P < 0.01) and returned to the control level at 12 h (0.04 ± 0.01 vs 0.05 ± 0.02, P > 0.05). In sFas assay, there was no significant difference between P group and C group (3.16 ± 0.75 vs 3.31 ± 0.80, 4.05 ± 1.08 vs 4.32 ± 1.11, 5.93 ± 1.52 vs 5.41 ± 1.47 and 4.62 ± 1.23 vs 4.44 ± 1.16, respectively, P > 0.05, for all). Comparison of P group and C group, the pathological changes were aggravated significantly in P group. Immunohistochemistry staining show the expression of Fas was absent in normal intestinal tissues, however, it gradually increased after induction of pancreatitis in intestinal tissue, then reached their peaks at 12 h.
CONCLUSION: Fas were involved in the pathogenesis of pancreatitis associated intestinal injury. The mechanisms of Fas may be associated to Fas mediated T helper cell apoptosis.
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