Mild Acute Pancreatitis Patients Research Articles

Assessment of Severity of Acute Pancreatitis in Children: Systemic Inflammatory Response Syndrome (SIRS) Score

Acute pancreatitis (AP) is a prompt inflammatory process of the pancreas and it may be ranged from mild to severe pancreatitis with variable involvement of regional tissues and remote organ systems. Though there are many scoring systems for adults but scarce of scoring system for assessing the severity of acute pancreatitis among paediatric cases increase their suffering. Systemic Inflammatory Response Syndrome (SIRS) can be useful for assessing the severity of acute pancreatitis in children. It is reported that SIRS has good sensitivity, specificity, positive predictive value and negative predictive value. The aim of this study was to assess the severity of acute pancreatitis in paediatric cases from the scores of SIRS. This cross-sectional descriptive study was coducted in the Department of Paediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh for a period of 1.5 years from May 2019 to October 2020. A total of 25 children with acute pancreatitis were selected purposively and SIRS was evaluated. The sensitivity, specificity, positive predictive value and negative predictive value of SIRS was calculated. Out of 25 acute pancreatitis children, 18 (mean age, 10.27±4.0 years) were diagnosed as mild AP and 7 (mean age, 10.54 ±4.0 years) as severe AP. Fourteen (56.0%) children were male and less than half 11 (44%) of children had pallor and most of them 23 (92%) had abdominal tenderness. There was no statistically significant difference between mild and severe AP in terms of serum lipase, amylase, BUN and CRP (p > 0.05). SIRS score was ≥2 in 7 (100%) severe AP patients and score was ≥2 in 4 (22.2%) mild AP patients and it was statistically significant (p=0.001). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of SIRS score in predicting severe acute pancreatitis was 100%, 77.8%, 63.6%, 100% and 84% respectively. This study finds that SIRS score can effectively assess the severity of acute pancreatitis in the paediatric age group. Systemic Inflammatory Response Syndrome (SIRS) score at admission can be used to assess the severity of acute pancreatitis. Bangladesh Med J. 2022 Sept; 51(3): 10-17

Gene Expression Profiling: Identification of Novel Pathways and Potential Biomarkers in Severe Acute Pancreatitis.

Determining the risk of developing severe acute pancreatitis (AP) on presentation to hospital is difficult but vital to enable early management decisions that reduce morbidity and mortality. The objective of this study was to determine global gene expression profiles of patients with different acute pancreatitis severity to identify genes and molecular mechanisms involved in the pathogenesis of severe AP. AP patients (n = 87) were recruited within 24 hours of admission to the Emergency Department and were confirmed to exhibit at least 2 of the following features: (1) abdominal pain characteristic of AP, (2) serum amylase and/or lipase more than 3-fold the upper laboratory limit considered normal, and/or (3) radiographically demonstrated AP on CT scan. Severity was defined according to the Revised Atlanta classification. Thirty-two healthy volunteers were also recruited and peripheral venous blood was collected for performing RNA-Seq. In severe AP, 422 genes (185 upregulated, 237 downregulated) were significantly differentially expressed when compared with moderately severe and mild cases. Pathway analysis revealed changes in specific innate and adaptive immune, sepsis-related, and surface modification pathways in severe AP. Data-driven approaches revealed distinct gene expression groups (endotypes), which were not entirely overlapping with the clinical Atlanta classification. Importantly, severe and moderately severe AP patients clustered away from healthy controls, whereas mild AP patients did not exhibit any clear separation, suggesting distinct underlying mechanisms that may influence severity of AP. There were significant differences in gene expression affecting the severity of AP, revealing a central role of specific immunological pathways. Despite the existence of patient endotypes, a 4-gene transcriptomic signature (S100A8, S100A9, MMP25, and MT-ND4L) was determined that can predict severe AP with an accuracy of 64%.

STUDY OF ALBUMIN, CALCIUM AND ALBUMIN CORRECTED CALCIUM WITH SEVERITY OF ACUTE PANCREATITIS

Aim: The purpose of this study to evaluate the level of serum Albumin, Calcium and Albumin corrected calcium with severity of acute pancreatitis. Material and methods:The study was conducted in Department of Biochemistry in association with Department of Gastroenterology, Mahatma Gandhi Medical College & Hospital. In present study out of 133 patients diagnosed for Acute Pancreatitis; total 115 patients (n=115) of either gender of 18 to 65years age groups were enrolled for the study. Patients with history of any acute or chronic illness like: - Hyperparathyroidism, Diabetes Mellitus, Impaired renal function, Malnourished, Pregnant and lactating women and patients on calcium supplements were excluded. Result: Mean level of calcium decreased with progression in disease severity (p≤0.001).The mean Albumin Corrected Calcium was also signicantly lower in the patients presenting with severe and moderate acute pancreatitis compared with the mild acute pancreatitis patients (p≤0.0001). Conclusion: The study recommends hypocalcaemia and hypoalbuminemia as independent risk factors of progression towards severe pancreatitis. Similarly, albumin corrected calcium is suggested as a reliable marker for severity of pancreatitis.

Current usage status of somatostatin and its analogs and trypsin inhibitors: a real-world study of 34,654 Chinese adult patients with acute pancreatitis.

Although somatostatin and its analogs and trypsin inhibitors (TSI) are widely recommended for acute pancreatitis (AP), there is a lack of high-quality multicenter trials that validate these drug classes. We aimed to examine the current usage status of somatostatin and its analogs and TSI in Chinese adult AP patients. We conducted a retrospective study which collected information for adult patients who were diagnosed with AP from January 1, 2015 to June 30, 2017 at 192 hospitals in China. Subsequently, we conducted a statistical analysis of the baseline information of patients, and revealed the usage of somatostatin, octreotide, ulinastatin, and gabexate. Thereafter, we stratified AP by severity and analyzed the current status of treatment. A total of 34,654 patients were included in this study. Mean age of patients was 49.9 years and 63% were males. Fifty-five percent of mild AP patients opted to receive octreotide, while 53.66% and 64.61% of moderate AP and severe AP patients respectively opted to receive somatostatin. At treatment initiation, somatostatin was mainly prescribed for mild and moderate AP patients, which were 723 and 894 daily defined doses (i.e., defined dose per day for a drug used by every 1,000 patients). Ulinastatin was mainly prescribed for severe AP patients, with a prescription volume of 1,230 daily defined doses. The consumption of ulinastatin in later stages of severe AP treatment was significantly greater than other drugs. Somatostatin analogs and TSI are widely used as therapeutic drugs for AP treatment in China, with usage beginning at the early stages of the disease and lasting on average for 1 week. Of these drugs, somatostatin and octreotide were identified as the most commonly-used drugs, while ulinastatin was found to be widely used at the late stages of severe AP.

Acute pancreatitis in Chile: A multicenter study on epidemiology, etiology and clinical outcome. Retrospective analysis of clinical files

BackgroundEpidemiology of acute pancreatitis (AP) is variable in different geographical regions. ObjectivesTo compare etiology and severity of AP to published data from South America and the rest of world, study impact of demographical factors and treatment on its outcome in Chilean hospitals. MethodsMulticenter observational study. Data of consecutive patients with AP were collected at the moment of discharge from 11 centers and retrospectively analyzed. ResultsData of 962 patients were included in the analysis, 447 men and 515 women. Mean age was 48,2 years. Biliary etiology was significantly more frequent in women (70%) than in men (52%). Conversely, alcohol was responsible for about 17% of AP in men but exceptional in women. Mild AP was seen in 73.4%, moderately severe in 14.1% and severe in 13%. The overall mortality was 2.5% (24 of 962): 0.3%, 3.1% and 15.1% in mild, moderately severe and severe cases, respectively. No difference was found in the mortality and severity of biliary versus alcoholic AP, while hypertriglyceridemia induced AP was more severe, without increased mortality. Severity and mortality increased with age. ERCP was performed in 16% of biliary pancreatitis. Adherence to main guidelines was heterogeneous: more than half of mild AP patients were admitted to critical care units and antibiotics were used in about 25% them. ConclusionThis is the first multicenter study in Chile on AP. When compared to literature, we found similar severity distribution and an acceptably low mortality. Biliary etiology was dominant, but alcohol was also important in men.

Reliability and validity of the Chinese version of Gastroparesis Cardinal Symptom Index Revised

Objective To introduce the Gastrointestinal Symptoms Index Revised (GCSI-R) scale and verify its reliability and validity in mild acute pancreatitis patients. Methods Following the Brislin principle of translation, 2 nursing graduate students who passed CET-6 translated English version GCSI-R scale and 2 oversea graduated nursing experts in the nursing related field who were highly proficient in both Chinese and English did the backtranslation and made the cultural adjustments to the scale through expert consultation and pre-surveys. By convenience sampling, 99 patients with mild acute pancreatitis admitted in Pancrea Center in a ClassⅢ Grade A hospital in Jiangsu Province from January to May of 2018 were selected and tested the reliability and validity of the scale. Finally, 83 valid scales were included to analyze the reliability and validity of the revised version among the patients with mild acute pancreatitis. Results The Chinese version of scale consisted of 8 items with 3 dimensions (nausea/vomiting, early satiety, bloating) . The Chinese version of the GCSI-R scale had a Cronbach's α coefficient of 0.765, and the dimensions of Cronbach's α coefficients were 0.739, 0.739, and 0.725 respectively, and the test-retest reliability was 0.805. Evaluated by the committee of experts, the content validity of various items in the Chinese version of GCSI-R (S-CVI/Ave) on average was 0.90, and their content validity index (I-CVI) ranged 0.80 to 1.00. Exploratory factor analysis extracted a total of 3 common factors, which explained 72.17% of the total variance, and the factor load of each item on its common factor was >0.4. Conclusions The Chinese version of GCSI-R scale has good reliability and validity and can be used as a simple tool for self-assessment on gastrointestinal function in patients with acute pancreatitis during the early period of hospitalization. Key words: Pancreatitis; Gastrointestinal function; Gastroparesis; Score; Reliability; Validity

Plasma mtDNA Analysis Aids in Predicting Pancreatic Necrosis in Acute Pancreatitis Patients: A Pilot Study.

Specific plasma biomarkers in predicting pancreatic necrosis (PNec) are needed in treating acute pancreatitis (AP). To investigate the prognostic value of plasma mitochondrial DNA fragments (mtDNA) in patient with AP for PNec. AP patients with symptoms onset within 72h were prospectively enrolled from June 2015 through June 2017 and were assessed for PNec using contrast-enhanced CT scan. Plasma mtDNA concentration (specific mitochondrial gene ND1) was measured using qRT-PCR. Of the 74 AP patients included, significant higher median level of plasma mtDNA was found in severe AP patients than in mild AP patients and healthy controls, but not in moderately severe AP patients. Patients with PNec had higher level of plasma mtDNA than those without PNec (774.2 [IQR 397.6-2205.0] vs. 169.5 [IQR 73.6-683.4] pg/ml, P < 0.05). The area under the receiver operator characteristic curve (ROC-AUC) of mtDNA for predicting PNec was higher than that of CRP (0.813 [95% CI 0.705-0.895] vs. 0.678 [95% CI 0.558-0.783]). Using a cutoff value of 302.5pg/ml, the sensitivity and specificity for diagnosing PNec were 90.9 and 68.3%, respectively. Finally, plasma mtDNA levels decreased significantly after continuous renal replacement therapy (717.7 [IQR 307.00-1370.00] vs. 237.5 [IQR 117.20-464.80] pg/ml, P < 0.01). Elevated plasma mtDNA content in AP patients may be used as a more accurate early predictor of PNec in contrast to traditional CRP.

Which Patients with Mild Acute Pancreatitis Require Prolonged Hospitalization?

Objectives:In our experience, a subset of mild acute pancreatitis (AP) patients, as defined by the Revised Atlanta Classification, has longer than expected hospitalization. Our aims are to report the prevalence of patients with mild AP who have a prolonged length of stay (LOS), evaluate the etiology, thoroughly phenotype, and finally compare this subset to those with expected LOS.Methods:Patients admitted with AP from 2003 to 2015 were prospectively enrolled into this cohort study. LOS ≥8 days was considered as prolonged LOS. Data on demographics, clinical and laboratory variables, management, and outcomes was both prospectively and retrospectively collected. Continuous variables were compared using the nonparametric t-test (Wilcoxon's test) and categorical variables using the Pearson’s χ2 test.Results:Among 231 enrolled mild AP patients, 46 (20%) had a prolonged LOS (≥8 days). The main determinants of prolonged LOS included ongoing pancreatitis-related symptoms (n=31, 67.4%) and performance of cholecystectomy (n=11, 23.9%). When compared to patients with expected LOS (<8 days, n=185), patients with prolonged LOS due to ongoing symptoms (n=31) were more likely to have systemic inflammatory response syndrome at 48 h from admission (37% vs. 13.4%, P<0.001), a prolonged fasting period (6.6 vs. 2.8 days, P<0.001), and need for nutritional support (30% vs. 1.6%, P<0.001).Conclusions:About 20% of patients with mild AP have a longer than expected hospital stay, mostly attributed to ongoing pancreatitis-related symptoms. An early decision (at 72 h) for enteral nutrition support in these patients needs to be explored so as to shorten hospitalization and reduce cost of care.

Elevated Serum miR-7, miR-9, miR-122, and miR-141 Are Noninvasive Biomarkers of Acute Pancreatitis.

Background It has been reported that several microRNAs (miRNAs), such as miR-141, miR-9, and miR-122, are involved in the regulation of pancreatitis-related proteins or that their levels change in acute pancreatitis (AP) animal models. However, the serum levels, as well as the clinical diagnostic and prognostic values, of these miRNAs in AP patients remain unclear. Furthermore, as a pancreas- (islet) enriched miRNA, miR-7 was reported to be downregulated in AP patients, which requires further verification. Methods The levels of miR-7, miR-9, miR-122, and miR-141 were examined and compared using qRT-PCR among 80 severe AP patients, 80 mild AP patients, and 74 healthy controls. Results The serum levels of these four miRNAs were increased markedly in the AP patients compared with the controls, and these levels decreased significantly after effective therapy. Particularly, the level of miR-7 was higher in severe AP patients than in mild AP patients. ROC curve analysis demonstrated that four miRNAs could be used as potential biomarkers for AP. Moreover, these miRNAs showed strong positive correlations with CRP, which may be associated with inflammation. Conclusions The serum miR-7, miR-9, miR-122, and miR-141 levels were increased in AP patients. These 4 miRNAs may represent diagnostic and prognostic biomarkers for AP.

Identification of serum microRNAs as diagnostic and prognostic biomarkers for acute pancreatitis

Background/objectivesTo identify serum microRNA (miRNA) as diagnostic and prognostic biomarkers for acute pancreatitis (AP). Materials and methodsSera microRNA expression was profiled from 12 AP patients with varying disease severity and three healthy controls. Differentially expressed miRNAs were validated in a larger cohort of patients and controls. The diagnostic and prognostic potentials of differentially expressed miRNAs were evaluated using receiver operating characteristic (ROC) curve analysis and compared to that of classic prognostic markers for AP. ResultsmiRNA microarray analyses identified 205 differentially expressed miRNAs between sera from AP patients and that from controls. Nine miRNAs were differentially expressed between severe and mild AP patients. Further validation confirmed the down-regulation of miR-92b, miR-10a, and miR-7 in AP patients, and ROC analysis revealed that these miRNAs can differentiate AP from health cases. Furthermore, the serum miR-551b-5p level was significantly higher in patients with disease complications or a low plasma calcium level. ROC analysis showed that the serum miR-551b-5p level can distinguish between severe and mild AP. ConclusionThe expressions of miR-92b, miR-10a, and miR-7 in AP might be used for the early diagnosis of AP and miR-551b-5p may be used for predicting AP severity.

Nutrition acute pancreatitis

Acute pancreatitis is a common and potentially severe disease where nutritional support does affect its development in a way it may be considered a treatment in severe cases. These include around 20% of patients and present mortality rates of 8%-39%. In mild acute pancreatitis patients are prescribed nil per os at admission and advance diet in a progressive manner the following days. Although early introduction of diet has proven to shorten the length of stay, it is still not clear when and how to introduce diet. Severe disease is a hypercatabolic situation which often appears in already malnourished patients. Early enteral nutrition has shown a significative benefit over parenteral nutrition in terms of infection rates, hyperglycemia and mortality rates. This benefit may be related to a decrease in bacterial intestinal translocation. Nasoyeyunal tube feeding is the preferred site, but there are trials supporting nasogastric tubes, a more feasible election. The following lines offer an up to date review of nutritional management in acute pancreatitis, trying to answer in a clear and practical way to the most frequent problems arising in the day to day management of this disease.

Nutrición en pancreatitis aguda

Acute pancreatitis is a common and potentially severe disease where nutritional support does affect its development in a way it may be considered a treatment in severe cases. These include around 20% of patients and present mortality rates of 8%-39%. In mild acute pancreatitis patients are prescribed nil per os at admission and advance diet in a progressive manner the following days. Although early introduction of diet has proven to shorten the length of stay, it is still not clear when and how to introduce diet. Severe disease is a hypercatabolic situation which often appears in already malnourished patients. Early enteral nutrition has shown a significative benefit over parenteral nutrition in terms of infection rates, hyperglycemia and mortality rates. This benefit may be related to a decrease in bacterial intestinal translocation. Nasoyeyunal tube feeding is the preferred site, but there are trials supporting nasogastric tubes, a more feasible election. The following lines offer an up to date review of nutritional management in acute pancreatitis, trying to answer in a clear and practical way to the most frequent problems arising in the day to day management of this disease. (Nutr Hosp. 2012;27:333-340) DOI:10.3305/nh.2012.27.2.5408

Prevalence of and Factors Determining Prolonged Length of Stay in Mild Acute Pancreatitis

Background: Patients with acute pancreatitis (AP) who do not have severe disease (characterized by pancreatic necrosis and/or organ failure) are expected to have a speedy recovery and short hospital stay (i.e. ≤7 days). However, it is unclear how often patients with mild AP stay longer in the hospital and what factors determine their prolonged length of stay (LOS). Aim: To determine what fraction of patients with mild AP require hospitalization for >7 days and determine the factors associated with prolonged hospitalization. Methods: Patients with AP who were admitted from July 2003 to August 2010 were prospectively enrolled. Mild AP with prolonged stay was defined as absence of systemic (i.e. persistent organ failure) and/or local complications (i.e. pancreatic necrosis), and a LOS of >7 days. The potential factors responsible for prolonged hospitalization were noted and compared with mild AP patients whose LOS was≤7 days: pancreatitis-related symptoms (i.e. persistent abdominal pain, inability to tolerate p.o. intake, inflammatory changes on imaging); nosocomial infections/pulmonary emboli; intervention (i.e. laparoscopic cholecystectomy, or pseudocyst drainage); comorbid conditions, which decompensated during hospital stay, and other. Ranson's and APACHE-II scoring systems measured at 48 hours from admission were evaluated as potential predictors of LOS. Results: Overall, 176 out of 256 patients were classified as having mild AP. Of these patients, 53 (30%) had a hospital stay of >7 days. The clinical characteristics of patients with mild AP and prolonged stay are seen in Table 1. Patients with mild AP and prolonged stay tend to be older and with more prominent inflammatory response to pancreatic injury (manifested as higher admission clinical scores), when compared to those with mild AP and LOS ≤7 days. Sex distribution, etiology of AP, and BMI are similar in the two groups. Prolonged stay was a result of pancreatitis-related symptoms in 51% of these patients, of infections/pulmonary emboli in 15%, interventions in 13%, and comorbidities in 13% (Table 2). Fourty-eight hour Ranson's and APACHE-II scores revealed low to moderate accuracies in predicting prolonged stay with an area under the curve (AUC) of 0.62 and 0.63, respectively. Conclusions: About one-third patients with mild AP have prolonged hospitalization with an average stay of 15 days. Studies focusing on this group of patients are needed to determine targeted measures to improve symptoms, prevent complications and shorten LOS. Comparison of characteristics of patients with mild AP and LOS ≤7 days and those with mild AP and prolonged stay

Update of the Atlanta Classification of Severity of Acute Pancreatitis: Should a Moderate Category Be Included?

Background: Persistent and multiple organ failure (POF and MOF) are predictive of death in acute pancreatitis (AP). Local complications without organ failure are associated with morbidity but a low risk of mortality. Aim: To design a three-category classification of AP severity and to compare it with the Atlanta Classification (AC) in terms of morbidity and mortality. Method: Severe AP was defined as death, POF (148 h) or MOF. Moderate AP was defined as the presence of acute collections and/or pancreatic necrosis. Mild AP was defined by exclusion. We compared this classification with AC in 144 episodes of AP. Results: In the three-category classification, severe AP was associated with significantly more frequent intensive care unit admission, invasive treatment and mortality than moderate and mild AP (p < 0.01). Severe AP patients required longer hospital stay and more nutritional support than mild AP patients (p < 0.01). Patients with moderate AP had significantly longer hospital stay and more need for nutritional support than patients with mild AP (p < 0.01). Five patients died, all of them with MOF and/or POF. Conclusions: A three-category classification distinguishes three homogeneous groups of severity.

Angiopoietin-2, a Regulator of Vascular Permeability in Inflammation, Is Associated With Persistent Organ Failure in Patients With Acute Pancreatitis From the United States and Germany

Patients with severe acute pancreatitis (AP) typically develop vascular leak syndrome, resulting in hemoconcentration, hypotension, pulmonary edema, and renal insufficiency. Angiopoietin-1 (Ang-1) and 2 (Ang-2) are autocrine peptides that reduce or increase endothelial permeability, respectively. The aim of this study was to determine whether Ang-1 and/or Ang-2 levels are predictive biomarkers of persistent organ failure (>48 h) and prolonged hospital course. Banked serum from 28 patients enrolled in the Severity of Acute Pancreatitis Study at the University of Pittsburgh Medical Center (UPMC) and 58 controls was analyzed for Ang-1 and Ang-2 levels. Separately, serum from 123 patients and 103 controls at Greifswald University (GU), Germany was analyzed for Ang-2 levels. Angiopoietin levels were measured by enzyme-linked immunosorbent assay. In all, 6 out of 28 UPMC patients (21%) and 14 out of 123 GU patients (13%) developed persistent organ failure and were classified as severe AP. Ang-2 was significantly higher on admission in patients who developed persistent organ failure compared with those who did not in UPMC (3,698 pg/ml vs. 1,001 pg/ml; P=0.001) and GU (4,945 pg/ml vs. 2,631 pg/ml; P=0.0004) cohorts. After data scaling, admission Ang-2 levels showed a receiver-operator curve of 0.81, sensitivity 90%, and specificity 67% in predicting persistent organ failure. In addition, Ang-2 levels remained significantly higher in severe AP compared with mild AP patients until day 7 (days 2-4: P<0.005; day 7: P<0.02). Ang-1 levels were not significantly different between mild and severe AP patients on admission. Elevated serum Ang-2 levels on admission are associated with and may be a useful biomarker of predicting persistent organ failure and ongoing endothelial cell activation in AP.

Application of endoscopic sphincterotomy in acute pancreatitis with fluid collection: A prospective study

To elucidate the role of endoscopic sphincterotomy (EST) in the treatment of acute pancreatitis. Ninety patients with acute pancreatitis were randomly divided into two groups: EST group and control group. All the patients underwent pancreatitis routine therapy, additionally the EST group was treated with EST and endoscopic naso-bile drainage (ENBD). The time of disappearance of abdominal symptoms and signs, normalization of amylase, hospitalization and absorption of acute fluid was recorded for all patients. The time of disappearance of abdominal pain, normalization of blood and urine amylase and hospitalization was significantly shorter in EST group than in control group. The ratios of disappearance of fluid in mild acute pancreatitis patients was significantly higher in EST group (51.52%, 84.85%, 90.91%, 93.94%) than in the control group (0%, 30.30%, 69.70%, 72.73%, P<0.01 or P<0.05). When the ratios of reduction of fluid in severe acute pancreatitis patients of the EST group were compared (8.33%, 58.33%, 83.33%, 91.67%) with those in the control group (0%, 8.33%, 25% and 41.67%), there were significant differences. The effect of EST+ENBD on acute pancreatitis with fluid is rather good.

Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis

Background & Aims: Macrophage migration inhibitory factor (MIF), originally described as an inhibitor of the random migration of macrophages, has been shown recently to be involved in the pathogenesis of several inflammatory diseases such as sepsis. The aim of this study was to clarify the role of MIF in acute pancreatitis (AP). Methods: Hemorrhagic necrotizing pancreatitis and edematous pancreatitis were induced by the injection of taurocholic acid (TCA pancreatitis) and cerulein (cerulein pancreatitis), respectively, on male Wistar rats. MIF levels in ascitic fluids, serum, and the organs were determined. The effects of anti-MIF antibody were examined on the prognosis of rats with TCA pancreatitis and of female CD-1 mice with choline-deficient, ethionine-supplemented, diet-induced model of severe AP. In addition, serum MIF levels in AP patients and in healthy controls were measured. Results: Serum and ascitic MIF levels in TCA pancreatitis were increased rapidly and decreased gradually thereafter. Ascitic MIF levels were also increased in cerulein pancreatitis, but to a lesser degree. MIF level was increased in the lung in TCA pancreatitis, but not in the pancreas and the liver. Prophylactic (1 hour before and immediately after induction) administration of anti-MIF antibody significantly improved the survival rate of rats with TCA pancreatitis. The survival rate of mice with severe AP was also improved significantly by the antibody treatment. Serum MIF levels were higher in severe AP patients than mild AP patients and healthy controls. Conclusions: These results suggest a role of MIF in the pathogenesis of severe AP.GASTROENTEROLOGY 2003;124:725-736