Pathogenesis Of Acute Pancreatitis Research Articles

Role of Immune Cells and Immune-Based Therapies in Pancreatitis and Pancreatic Ductal Adenocarcinoma

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.

A serum metabolomic investigation on lipoprotein lipase-deficient mice with hyperlipidemic pancreatitis using gas chromatography/mass spectrometry

Hypertriglyceridemia (HTG) is often associated with acute pancreatitis. The relationship between these diseases and the role that hypertriglyceridemia plays in acute pancreatitis pathogenesis remains to be elucidated. In the present study, in order to investigate the mechanisms of hyper-lipidemic acute pancreatitis (HLP), we established an animal model using lipoprotein lipase (LPL)-deficient heterozygous mice injected with caerulein. Susceptibility to pancreatitis in LPL-deficient heterozygous mice was compared with that of wild-type mice after intraperitoneal (i.p.) injections of caerulein by determining amylase release and pancreatic pathological scores. Furthermore, serum metabolome was detected through chemical derivatization followed by gas chromatography/mass spectrometry (GC/MS). GC/MS data were analyzed by orthogonal-projection to latent structures-discriminant analysis (OPLS-DA). Caerulein induced increased levels of serum amylase and more severe pancreatic inflammation in LPL-deficient mice compared to wild-type mice. HLP was discriminated more accurately from healthy controls by the metabolites, including valine, leucine and citrate. The metabolites included valine, leucine, citrate, malic acid, proline, tetradecanoic acid (14:0), glutamine and oleic acid (18:1). Changes in energy, fat and amino acid metabolism were also evident. In conclusion, LPL-deficient heterozygous mice with hypertriglyceridemia (HTG) exhibited enhanced susceptibility to acute pancreatitis. GC/MS data revealed differences between healthy and HLP mice. Therefore, this technique is novel and a useful tool for the study of the HLP pathogenetic mechanism.

Role of Oxidative Stress in the Pathogenesis of Pancreatitis: Effect of Antioxidant Therapy.

Oxidative stress plays an important role in the pathogenesis of acute pancreatitis. The exact pathogenesis of pancreatitis remains unknown but several mechanisms related to oxidative and inflammatory stress are implicated. It is reasonable to surmise that antioxidants would play a protective role in ameliorating the deleterious effects of pancreatitis. We have a wealth of data from animal models that reveal a positive correlation between antioxidant drugs and improved outcomes in experimental pancreatitis. Human clinical trials with antioxidants however, have disclosed conflicting results. We review the existing pathogenesis of pancreatitis related to oxidative stress and provide of a review of current trials with antioxidant therapy.

Effects of Hydrogen-Rich Saline on Taurocholate-Induced Acute Pancreatitis in Rat

Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). As an ideal exterminator of poisonous free radicals, hydrogen can clearly reduce the degree of oxidative damage caused by severe acute pancreatitis (SAP) and lessen the presence of inflammatory cytokines. The aim of this study was to investigate the effects and mechanism of hydrogen-rich saline on SAP in rats. Serum TNF-α, IL-6, and IL-18 and histopathological score in the pancreas were reduced after hydrogen-rich saline treatment. Malondialdehyde (MDA) and myeloperoxidase (MPO) contents were obviously reduced, while superoxide dismutase (SOD) and glutathione (GSH) contents were increased after hydrogen-rich saline treatment. The expression of mRNA of tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in the pancreas was reduced in hydrogen-rich saline treated group. In conclusion, intravenous hydrogen-rich saline injections could attenuate the severity of AP, probably via inhibiting the oxidative stress and reducing the presence of inflammatory mediators.

Pathogenesis of Acute Pancreatitis

여러 가지 원인이 급성 췌장염을 일으키나 각각의 요인들이 어떤 메커니즘으로 급성 췌장염을 유발하는지에 대한 이해는 급성 췌장염의 원인을 정확히 파악하고 치료하는 데 도움이 될 수 있다. 대표적인 원인 인자로는 만성 알코올 남용과 담석을 꼽을 수 있으며 그 밖에 CFTR mutation과 연관된 가족성 췌장염을 생각해 볼 수 있다. 심한 형태인 괴사성 췌장염에 관해서는 췌장효소의 활성화, 췌장 미세혈관의 손상, 염증인자의 분비가 췌장의 손상과 괴사를 악화시키며 심한 췌장 손상을 받은 일부 환자에서는 전신성 염증반응 증후군까지 진행될 수 있는데 이는 염증소견을 보이는 췌장에서 분비된 활성화된 췌장효소와 사이토카인이 전신으로 순환하면서 발생한다고 볼 수 있다. 일반적으로는 보상화된 항염증 반응이 전신성 염증반응과 균형을 이루면서 회복이 되지만 이와 같은 균형이 깨지면 심한 장기 부전으로 인해 사망으로까지 이를 수 있다. 또한, 급성 췌장염의 경과 중 장내 세균의 전좌(translocation)로 인하여 심한 급성 췌장염 환자의 30%에서 췌장과 췌장주위에 세균감염이 발생할 수 있는데, 이 경우 다발성 장기부전으로 이어질 수 있다. 췌장염의 초기 과정에서는 선방 세포 내의 trypsinogen의 활성화가 중요한 역할을 하나 사망에까지 이르게 하는 전신적 염증 반응의 경우는 독립적인 인자들이 작용하므로 이에 대한 메커니즘 연구 및 그에 맞는 치료법에 대한 연구가 필요한 실정이다. 이와 같이 급성 췌장염은 사망에까지 이르게 할 수 있는 질환으로서 정확한 진단과 치료의 기반이 될 수 있는 급성 췌장염의 병태생리에 대한 이해와 연구가 중요하다.

Role of intestinal lymphatic system in pathogenesis of acute pancreatitis

Role of intestinal lymphatic system in pathogenesis of acute pancreatitis

Mechanisms of immunosuppression and interleukin 2 in complex treatment of severe acute pancreatitis

Event Abstract Back to Event Mechanisms of immunosuppression and interleukin 2 in complex treatment of severe acute pancreatitis Mariya Shavarova1* and Serge Chooklin2 1 Medical Centre, Ukraine 2 Medical University, Ukraine Introduction. In pathogenesis of acute pancreatitis the important role are play pro- and anti-inflammatory cytokines. Their disbalance leads to depletion of immunocompetent cells and defines the expressed secondary immunodeficiency, which after 7-14 days becomes a leading pathogenic link of severe acute pancreatitis (SAP). Therefore adequate immunotherapy may play obvious role in complex treatment of this severe pathology. Materials and Methods. Plasma levels of IL-2, IL-4, IL-8, TNF-α, populations of lymphocytes were measured in 36 patients with SAP. Twenty patients received in complex therapy recombinant interleukin-2 in a dose of 3 million МО. Sixteen patients examined as control. Results. The mean value of serum all cytokines levels in patients with acute pancreatitis was significantly higher than in healthy volunteers. The lymphocyte count was decreased below the normal range, and was significantly negatively correlated with severe score. CD4- and CD8-positive lymphocyte counts on admission and the lymphocyte count on day 14 after admission may be useful for predicting infection. Changes of cytokines status after interleukin 2 therapy are noted too. Authentic levels depression of all cytokines in peripheral blood is established. The level of IL-2 tended to normalisation in comparison with a disease debut, but remains lower, than in healthy donors. After therapy normalization of Т lymphocytes level is noticed, that testified to indemnification of cellular link of immunity. Conclusion. A significant depletion of circulating lymphocytes was found in severe acute pancreatitis with infectious complications. Use of interleukin 2 in complex treatment of severe pancreatitis is expediently for correction immunoparalysis and prevention of purulent-septic complications. Keywords: acute pancreatitis, Lymphocytes, Interleukin-2, Cytokines, Immunosuppression Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Shavarova M and Chooklin S (2013). Mechanisms of immunosuppression and interleukin 2 in complex treatment of severe acute pancreatitis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00781 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Mariya Shavarova, Medical Centre, Lviv, Ukraine, docihor@ukr.net Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract Supplemental Data The Authors in Frontiers Mariya Shavarova Serge Chooklin Google Mariya Shavarova Serge Chooklin Google Scholar Mariya Shavarova Serge Chooklin PubMed Mariya Shavarova Serge Chooklin Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Central role of mitochondrial injury in the pathogenesis of acute pancreatitis

Acute pancreatitis is an inflammatory disease with no specific treatment. One of the main reasons behind the lack of specific therapy is that the pathogenesis of acute pancreatitis is poorly understood. During the development of acute pancreatitis, the disease-inducing factors can damage both cell types of the exocrine pancreas, namely the acinar and ductal cells. Because damage of either of the cell types can contribute to the inflammation, it is crucial to find common intracellular mechanisms that can be targeted by pharmacological therapies. Despite the many differences, recent studies revealed that the most common factors that induce pancreatitis cause mitochondrial damage with the consequent breakdown of bioenergetics, that is, ATP depletion in both cell types. In this review, we summarize our knowledge of mitochondrial function and damage within both pancreatic acinar and ductal cells. We also suggest that colloidal ATP delivery systems for pancreatic energy supply may be able to protect acinar and ductal cells from cellular damage in the early phase of the disease. An effective energy delivery system combined with the prevention of further mitochondrial damage may, for the first time, open up the possibility of pharmacological therapy for acute pancreatitis, leading to reduced disease severity and mortality.

Platelet Activation in Acute Pancreatitis

The aim of this study was to assess the functional state of platelets in patients with mild acute pancreatitis and severe acute pancreatitis (S-AP). The number of platelets and their morphological parameters were measured with Advia 2120. β-Thromboglobulin and platelet factor 4 concentrations were determined by enzyme-linked immunosorbent assay method. To evaluate the expression of platelet glycoproteins, flow cytometry method was used. At the time of admission, a multiparameter evaluation of the platelets' function in AP patients showed enhanced platelet activation, which was reflected by an increase in the number of large platelets, concentration of degranulation markers (platelet factor 4 and β-thromboglobulin), expression of glycoprotein (Gp) IIb/IIIa, and decreased mean platelet component. Only in S-AP patients at day 1 a decreased number of platelets and high expression of P-selectin and GpIa were observed, which may suggest their prognostic value. At day 30, the procoagulation state was still present in S-AP patients, because of increased platelets and number of large platelets as well as high GpIIb/IIIa expression. These results may indicate an important role of platelet activation in the pathogenesis of acute pancreatitis and the development of complications in S-AP.

Pathogenic mechanisms of acute pancreatitis

In this article, recent advances in the pathogenesis of acute pancreatitis have been reviewed. Pathologic intra-acinar trypsinogen activation had been hypothesized to be the central mechanism of pancreatitis for over a century. This hypothesis could be explored for the first time with the development of a novel mouse model lacking pathologic intra-acinar trypsinogen activation. It became clear that intra-acinar trypsinogen activation contributes to early acinar injury, but local and systemic inflammation progress independently during pancreatitis. Early intra-acinar nuclear factor kappa B (NFκB) activation, which occurs parallel to but independent of trypsinogen activation, may be crucial in pancreatitis. Although the mechanism of NFκB and trypsinogen activation is not entirely clear, further insights have been made into key pathogenic cellular events such as calcium signaling, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, autophagy and impaired trafficking, and lysosomal and secretory responses. Cellular intrinsic damage-sensing mechanisms that lead to activation of the inflammatory response aimed at repair, but lead to disease when overwhelmed, are beginning to be understood. New findings necessitate a paradigm shift in our understanding of acute pancreatitis. Intra-acinar trypsinogen activation leads to early pancreatic injury, but the inflammatory response of acute pancreatitis develops independently, driven by early activation of inflammatory pathways.

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis?

To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.

The role of calcium in acute pancreatitis

Until recently, it was unclear whether calcium is more than a bystander in the development of acute pancreatitis. Now important evidence has been accumulated supporting a pivotal role of intracellular levels of calcium in the early pathogenesis of the disease. A sustained increase of cytosolic calcium concentrations, as observed in various models of acute pancreatitis, was identified as sabotaging crucial cellular defense mechanisms and initiating premature trypsinogen activation. These processes lead the acinar cell to necrosis, with spillage of activated proteases into the interstitial space, affecting surrounding acinar cells and initiating a vicious circle that ends in macroscopic acute pancreatitis and systemic inflammatory response syndrome. Comprehensive knowledge of the pathobiology of cytosolic calcium in the pancreatic acinar cell is leading to the understanding of coherent molecular pathways of early events in the pathogenesis of acute pancreatitis and is opening horizons for research into directly targeted therapeutic agents.

Recurrent pancreatitis in ornithine transcarbamylase deficiency

Ornithine transcarbamylase (OTC) deficiency is a urea cycle defect with varying frequency and severity of episodes of hyperammonemia. We report three patients with OTC deficiency with recurrent pancreatitis. The pathogenesis of acute pancreatitis in this patient population requires further elucidation. Pancreatitis significantly affected dietary/metabolic management and increased frequency of hospitalizations.

Chemokine receptor CXCR3 is involved in the acute pancreatitis-associated lung injury

Acute pancreatitis is a common disease, which is divided into mild pancreatitis and severe pancreatitis. For the latter, a systemic inflammatory response may occur and lead to distant organ damage and the development of multiple organ dysfunction syndrome (MODS), which accounts for significant morbidity and mortality in humans. Chemokines and their receptors are being believed to play a pivotal role in the pathogenesis of acute pancreatitis. Chemokine receptor CXCR3 is reported to be involved in acute tissue injury, for example acute lung injury induced by cigarette smoking, but its role in acute pancreatitis is not yet known. In this study, two animal models of acute pancreatitis (cerulein- and arginine-induced pancreatitis) were applied in CXCR3−/− mice and wild-type mice, in order to explore the role of CXCR3 in acute pancreatitis. Serum amylase, lipase and histological observations revealed that CXCR3 knockout did not affect the severity of acute pancreatitis. However, edema and inflammatory cell infiltrate in the lung tissue were attenuated in CXCR3−/− mice when acute pancreatitis was induced. In conclusion, chemokine receptor CXCR3 is not involved in acute pancreatic injury, but has a connection with acute pancreatitis-associated lung injury. Acute pulmonary injury is attenuated in CXCR3 knockout mice in experimental acute pancreatitis.

Hypertriglyceridemia Aggravates ER Stress and Pathogenesis of Acute Pancreatitis

Endoplasmic reticulum (ER) stress and hypertriglyceridemia (HTG) have been implicated in acute pancreatitis (AP). For cellular model, rat exocrine acinar cells were preincubated with palmitic acid (0.05 or 0.1 mmol/L, 3 h) and stimulated with a cholecystokinin analog, CCK-8 (100 pmol/L, 30 min). For animal model, rats fed a high-fat diet to cause HTG and AP was induced by injection of caerulein (20 μg/kg). Injury to pancreatic cells was estimated by measuring amylase secretion, intracellular calcium concentration, apoptosis and histological changes. Expression of genes involved in ER stress-induced unfolded protein response (UPR) was monitored by RT-PCR and immunohistology. In CCK-8 stimulated rat acinar cells, preincubation with PA caused an increased secretion of amylase, a higher and prolonged accumulation of intracellular calcium and increased apoptosis. Rats on high-fat diet had significantly elevated serum triglyceride levels. Induction of AP led to increased apoptosis in pancreatic tissue on high-fat diet than controls. For favoring HTG, expression of UPR components, GRP78/Bip, XBP-1, GADD153/CHOP and caspase-12 was upregulated. Levels of markers of AP pathogenesis and components of UPR were elevated in the presence of excess fatty acids in pancreatic acinar cells. HTG appears to aggravate ER-stress and pathogenesis of AP.

Role of Macrophages and Substance P in the Pathogenesis of Acute Pancreatitis

Summaryplays a major role in the pathophysiology of acute pancreatitis (AP). It is an acute inflammatory process of the pancreas, with variable involvement of other regional tissues or remote organ systems. The process of acute inflammation involves cells already present in all tissues, mainly resident macrophages and other cells. Inflammatory mediators believed to participate in the pathophysiology of this condition include: tumor necrosis factor-α, interleukin (IL)-6, IL-1β, IL-10, platelet activating factor, intercellular adhesion molecule-1, IL-8, monocyte chemotactic protein-1, complement component C5a, hydrogen sulfide, neutral endopeptidase and nuclear factor κB. Apart from these mediators, the role of substance P (SP) in the pathogenesis of AP has been described. SP is a neuropeptide that is released from nerve endings in many tissues and acts as a pro-inflammatory mediator in many inflammatory states including AP. This review focuses on the role of macrophages and SP in the pathogenesis of AP. Immunogastroenterology 2012; 1:90-99

Systematic review of diet in the pathogenesis of acute pancreatitis: A tale of too much or too little?

Background/Aim:The role of diet as the cause of acute pancreatitis (AP) has been suggested. The aim of the current review was to determine if there exists sufficient evidence linking nutrition, or the lack of it, to the pathogenesis of AP.Patients and Methods:A systematic search of the scientific literature was carried out using Embase, PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials for the years 1965 - 2011 to obtain access to studies involving dietary factors and the pathogenesis of AP.Results:A total of 17 studies were identified describing diet and AP. These included 12 human and 5 animal studies. 8 reports were found to link malnutrition and/or refeeding to the pathogenesis of AP. Two studies found an increased consumption of fats and proteins in patients with alcohol-related AP while 1 study noted a lesser intake of carbohydrate in patients. However, none of these differences attained statistical significance. A recent prospective case-control study found a significantly higher risk for AP amongst patients eating par-boiled rice and fresh water fish.Conclusions:Evidence from literature does not appear to support the role of diet as a single bolus meal as a cause for AP. Prolonged consumption of diets rich in proteins and fats may work synergistically with gallstones / alcohol to trigger an attack of AP indicating a possible role of diet as a cofactor in the development of AP possibly by lowering the threshold needed by these other agents to lead to the attack of AP.

Serum Proinflammatory Cytokine Levels and White Blood Cell Differential Count in Patients with Different Degrees of Severity of Acute Alcoholic Pancreatitis

Several studies suggest that cytokines and neutrophils play an important role in the pathogenesis of acute pancreatitis (AP). The AIM OF THE STUDY was to assess the systemic release of proinflammatory cytokines and WBC (white blood cells) count with differential in patients with acute alcoholic pancreatitis (AAP) and to characterize the differences between patients with mild and severe forms of the disease. Thirty-five patients with the mild form of acute alcoholic pancreatitis (MAAP) were compared to 11 patients with severe acute alcoholic pancreatitis (SAAP). Serum levels of IL-6, IL-8, IL-12p40 and WBC differential count were measured every second day during the first week after admission. During the course of the study, the average level of IL-6 was significantly (p<0.05) higher in patients with SAAP than in patients with the mild form of the disease (MAAP). Serum levels of IL-8 and IL-12p40 on admission were higher in patients with SAAP than in patients with MAAP but the difference was not statistically significant. Of all the types of WBCs, neutrophils were significantly (p<0.05) elevated the entire time in SAAP patients when compared to patients with MAAP on 5th and 7th day from admission to hospital. Patients with SAAP had significantly higher proinflammatory cytokine IL-6 levels and neutrophil counts than patients with MAAP. The results suggest that proliferation and overstimulation of this subset of leukocytes might contribute to the development of the systemic inflammatory response in patients with SAAP.

Experimental and clinical evidence of antioxidant therapy in acute pancreatitis

Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery. In recent years, substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents. Some of these antioxidants have been found beneficial in the treatment of AP in humans; however, at present there is insufficient clinical data to support the benefits of antioxidants, alone or in combination with conventional therapy, in the management of AP in humans. Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species. Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP. Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants. The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP.

Aprepitant, a Neurokinin-1 Receptor Antagonist, for Prevention of Post-ERCP Pancreatitis in High Risk Patients: A Randomized, Double-blind, Placebo Controlled Trial

Purpose: Post-ERCP pancreatitis can occur in up to 40% of high risk patients. Animal studies have demonstrated a role for substance P binding to neurokinin-1 receptor in the pathogenesis of acute pancreatitis. Our aim was to determine the efficacy of a neurokinin-1 receptor antagonist (aprepitant) to prevent post-ERCP pancreatitis in high risk patients. Methods: High risk adult patients (suspected sphincter of Oddi dysfunction, prior post-ERCP pancreatitis, expected sphincterotomy, and age<60 years) were randomized in a double-blind fashion to receive either 125 mg oral aprepitant or placebo 4 hours prior to ERCP, 80 mg 24 hours after the first dose, and then 80 mg 24 hours after the second dose. Patients were contacted at 48 hours and 7 days post-procedure. Imaging and laboratory studies were collected for all patients who sought medical attention. Chi-square test was used to compare incidence of post-ERCP pancreatitis between the two groups, defined as new onset or increased abdominal pain requiring admission that was associated with amylase or lipase >3 times upper limit of normal. Results: 34 patients were randomized to receive aprepitant and 39 patients received placebo. Baseline characteristics were similar between the two groups (Table 1). Incidence of acute pancreatitis was 7 in the aprepitant group and 7 in the placebo group (p = 0.77). 5 and 9 patients required hospitalization for abdominal pain that did not meet criteria for acute pancreatitis within 7 days post-procedure in the aprepitant and placebo groups respectively (p = 0.54). Mean age was 37 years among all patients who developed pancreatitis and 50 years among all patients who did not develop pancreatitis (p = 0.0027). Insertion of a pancreatic stent was not associated with a lower incidence of acute pancreatitis (p = 0.91).Table 1: Baseline characteristics of patients who received Aprepitant vs. placeboConclusion: Aprepitant did not lower incidence of post-ERCP pancreatitis in this study, but findings are limited by small sample size. Larger studies potentially using the recently available intravenous formulation are necessary to determine efficacy of aprepitant in this setting (we estimate a sample size of about 250 is necessary to detect difference in primary outcome with α = 0.05 and β = 0.2). This research was supported by an industry grant from Merck.