A Model to Predict the Severity of Acute Pancreatitis Based on Serum Level of Amylase and Body Mass Index.

BACKGROUND & AIMS: Most patients with acute pancreatitis (AP) develop mild disease, but up to 20% develop severe disease. Many clinicians monitor serum levels of amylase and lipase in an attempt to predict the disease course, but this strategy has not been recommended by practice guidelines. We performed a retrospective analysis to determine whether the percentage changes in amylase and lipase were associated with the severity of disease that developed in patients with AP. METHODS: We analyzed data collected from 182 consecutive patients with AP (21 with severe AP) admitted to the Cleveland Clinic from January 2008 through May 2010 (discover cohort). The association between 11 different factors and the severity of AP were assessed by univariable analysis; multivariable models were explored through stepwise selection regression. The percentage change in the serum level of amylase was calculated as follows: ([amylase day 1 - amylase day 2]/amylase day 1) × 100. The percentage change in amylase and body mass index (BMI) were combined to generate a z-score (z = -5.9 + [0.14 × BMI] + [0.01 × percentage change in amylase]), which was converted into a probability distribution called the change in amylase and BMI (CAB) score. The CAB score was validated using the AP database at the University of Pittsburgh Medical Center (140 patients, 35 with severe AP); we calculated p-scores for each patient and estimated the area under the receiver operating characteristics curve values. RESULTS: Univariable analysis identified the percentage change in the serum level of amylase and other factors to be associated significantly with the severity of AP (P = .017). The CAB score was best at identifying patients who developed severe AP, with an area under the receiver operating characteristics curve value of 0.79 in the discovery cohort (95% confidence interval, 0.71-0.87) and 0.731 in the validation cohort (95% confidence interval, 0.61-0.84). CONCLUSIONS: We developed a model to identify patients most likely to develop severe AP based on the percentage changes in serum level of amylase during the first 2 days after admission to the hospital and BMI.

Risk of and factors associated with readmission after a sentinel attack of acute pancreatitis.

BACKGROUND & AIMS: Few data are available on how many patients are readmitted to the hospital after attacks of acute pancreatitis. We aimed to determine the risk and factors that determine early (within 30 days) and late (after 30 days) readmission of patients with acute pancreatitis. METHODS: In a retrospective study, we collected and analyzed data on 127 surviving patients (median age, 53 y; 52% male; 83% white) hospitalized at the University of Pittsburgh Medical Center for a sentinel attack of acute pancreatitis, enrolled in the Severe Acute Pancreatitis Study from June 2003 through April 2010, and who had follow-up data. Information was collected on demographics, clinical profile, risk score at discharge (based on a recently developed scoring system), and details of readmissions during the follow-up period (median, 36 mo). RESULTS: Of the 127 patients, 52% were transfers from another care center and 32% required admission to the intensive care unit. Etiologies for pancreatitis were biliary (47%), idiopathic (13%), alcohol associated (12%), and others (28%). Pancreatic necrosis (28%), persistent organ failure (27%), and peripancreatic fluid collections (19%) were common. The median length of stay was 9 days. A total of 108 readmissions occurred for 43 patients (34%). Early readmissions (n = 21) occurred more frequently for patients with smoldering (ongoing) symptoms or local complications than for those without. Late readmissions (n = 22) occurred more frequently for patients with recurrent pancreatitis than for those without. Male sex, alcohol-associated disease, and severe disease increased the risks of readmission and recurrence. The risk for readmission was lower among nontransferred patients (23%) and patients without necrosis or organ failure (16%). Risk for readmission increased with the number of points on the weighted scoring system. CONCLUSIONS: Approximately one-third of patients hospitalized for acute pancreatitis are readmitted, usually as a result of smoldering symptoms, local complications, or recurrent attacks. Studies are needed to determine whether individualized discharge planning, with consideration of the etiology of acute pancreatitis, can reduce the risk for readmission.

Portosplenomesenteric venous thrombosis in patients with acute pancreatitis is associated with pancreatic necrosis and usually has a benign course.

BACKGROUND & AIMS: Although there are some data on prevalence of portosplenomesenteric venous thrombosis (PSMVT) in patients with acute pancreatitis (AP), the progression of PSMVT in patients who have and have not received anticoagulants has not been studied systematically. We evaluated the prevalence and natural history of PSMVT in a well-defined cohort of individuals with AP. METHODS: In a retrospective study, we analyzed data from the University of Pittsburgh Medical Center on 162 patients with a sentinel attack of AP from 2003-2010. Data were collected on patient demographics, clinical presentation, etiology, clinical course, and outcomes. One hundred twenty-two patients underwent contrast-enhanced computed tomography; the scans were reviewed to identify thromboses and/or narrowing of splanchnic veins (splenic, superior mesenteric, and portal). RESULTS: PSMVT was detected in 22 patients overall (14%; 18% among patients who underwent contrast-enhanced computed tomography). Median time to detection of PSMVT was 17 days (interquartile range, 11-40 days). PSMVT formed most frequently in the splenic vein (19 of 22, 86%), followed by portal (8 of 22, 36%) and superior mesenteric (6/22, 27%) veins. Development of PSMVT was associated with presence (21 of 22, 95%), location, and extent of pancreatic necrosis. Fifty-three percent of patients (21 of 40) with necrosis developed PSMVT. Anticoagulants were administered infrequently (6 of 22, 27%) and always for indications unrelated to PSMVT. Most patients with PSMVT developed collateral veins (19 of 22, 86%), and 27% (6 of 22) were found to have varices during endoscopic evaluation, but clot resolution was infrequent (2 of 22, 9%). No patient developed complications directly related to PSMVT. CONCLUSIONS: PSMVT develops in about half of patients with necrotizing AP and is rare in the absence of necrosis. Despite infrequent administration of anticoagulants, complications directly related to PSMVT are rare.

Management of Esophageal Inflammatory Myofibroblastic Tumor With Endoscopic Submucosal Dissection.

Inflammatory myofibroblastic tumors are rare tumors that have been described in virtually all organs. Even though they are extremely rare in the esophagus, several cases have been described in the literature. Surgical resection has been the therapeutic modality used in most of those cases. In this report, we describe a case of inflammatory myofibroblastic tumor that was successfully managed endoscopically for the first time with the endoscopic submucosal dissection technique.

Comparison of existing clinical scoring systems to predict persistent organ failure in patients with acute pancreatitis.

BACKGROUND & AIMS: It is important to identify patients with acute pancreatitis who are at risk for developing persistent organ failure early in the course of disease. Several scoring systems have been developed to predict which patients are most likely to develop persistent organ failure. We head-to-head compared the accuracy of these systems in predicting persistent organ failure, developed rules that combined these scores to optimize predictive accuracy, and validated our findings in an independent cohort. METHODS: Clinical data from 2 prospective cohorts were used for training (n = 256) and validation (n = 397). Persistent organ failure was defined as cardiovascular, pulmonary, and/or renal failure that lasted for 48 hours or more. Nine clinical scores were calculated when patients were admitted and 48 hours later. We developed 12 predictive rules that combined these scores, in order of increasing complexity. RESULTS: Existing scoring systems showed modest accuracy (areas under the curve at admission of 0.62-0.84 in the training cohort and 0.57-0.74 in the validation cohort). The Glasgow score was the best classifier at admission in both cohorts. Serum levels of creatinine and blood urea nitrogen provided similar levels of discrimination in each set of patients. Our 12 predictive rules increased accuracy to 0.92 in the training cohort and 0.84 in the validation cohort. CONCLUSIONS: The existing scoring systems seem to have reached their maximal efficacy in predicting persistent organ failure in acute pancreatitis. Sophisticated combinations of predictive rules are more accurate but cumbersome to use, and therefore of limited clinical use. Our ability to predict the severity of acute pancreatitis cannot be expected to improve unless we develop new approaches.

TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is a complex inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction syndrome (MODS). Tumor necrosis factor alpha (TNF-α) is a cytokine that may link inflammation to the systemic inflammatory response syndrome (SIRS), which usually precedes MODS. Small genetic cohort studies of the TNFA promoter in AP produced ambiguous results. We performed a comprehensive evaluation of TNFA promoter variants to assess both susceptibility to AP and risk of progression to MODS. METHODS: We prospectively ascertained 401 controls and 211 patients with AP that were assessed for persistent SIRS (>48 h) and MODS. MODS was defined as failure of ≥2 organ systems (cardiovascular, pulmonary, and/or renal) persisting more than 48 h. Subjects were genotyped by DNA sequencing and analyzed for SNPs at -1031 C/T (rs1799964), -863 A/C (rs1800630), -857 C/T (rs1799724), -308 A/G (rs1800629), and -238 A/G (rs361525). RESULTS: Twenty-three of 211 AP patients (11%) developed MODS. TNFA promoter variants were not associated with susceptibility to AP, but progression to MODS was associated with the minor allele at -1031C (56.5% vs. 32.4% P = 0.022, OR: 2.7; 95%CI: 1.12-6.51) and -863A (43.5% vs. 21.8% P = 0.022, OR: 2.76; 95%CI: 1.12-6.74). CONCLUSION: TNFA promoter variants do not alter susceptibility to AP, but rather the TNF-α expression-enhancing -1031C and -863A alleles significantly increased the risk of AP progression to MODS. These data, within the context of previous studies, clarify the risk of specific genetic variants in TNFA and therefore the role of TNF-α in the overall AP syndrome.

Hospitalizations for chronic pancreatitis in Allegheny County, Pennsylvania, USA.

BACKGROUND/AIMS: Population-based estimates for chronic pancreatitis (CP) are scarce. We determined incident CP hospitalization rates and the risk of pancreatitis-related readmissions in Allegheny County, Pennsylvania, USA. METHODS: We used Pennsylvania Health Care Cost Containment Council (PHC4) dataset to identify all unique White and Black Allegheny County residents with incident hospitalization for CP from years 1996-2005. We noted presence of alcoholism codes (from one year before index hospitalization until last contact) and pancreatitis-related readmissions until the third quarter of 2007. Age-, sex-, and race-adjusted (to US 2000 population) rates/100,000 were calculated. RESULTS: 988 unique County residents with incident hospitalization for CP were identified. Of these, 37.6% also received alcoholism codes. Overall hospitalization rate was 7.75/100,000 (95% CI 7.26-8.24), which remained stable throughout the study period. Patients with alcoholism codes were significantly younger (47.2 vs. 58.0 years), more likely to be male (71.4 vs. 36.6%), and Black (38.5 vs. 17.7%). Hospitalization rates were significantly higher (2.4-fold) in Blacks (vs. Whites), particularly for those with alcoholism codes. During follow-up (median 45 months), pancreatitis-related readmissions were common, significantly more so for patients with alcoholism codes. CONCLUSIONS: CP hospitalization rates over a one-decade period were stable. Readmissions were highest among patients with a diagnosis of alcoholism. and IAP.

SPINK1 N34S is strongly associated with recurrent acute pancreatitis but is not a risk factor for the first or sentinel acute pancreatitis event.

OBJECTIVES: Serine protease inhibitor Kazal type 1 (SPINK1) gene mutations have been associated with chronic pancreatitis of different etiologies; however, little is known about their role in the pathogenesis of acute pancreatitis (AP). Our aim was to study the prevalence of the SPINK1 N34S polymorphism in patients with sentinel and recurrent AP (RAP). METHODS: Patients with AP were enrolled, and genetic tests were carried out to detect the SPINK1 N34S polymorphism. Subjects without pancreatitis from the North American Pancreatitis Study were used as controls. RESULTS: A total of 188 patients (116 with sentinel AP and 72 with recurrent attacks) and 670 controls were evaluated. The SPINK1 N34S polymorphism was detected in 1 of 232 alleles in patients with sentinel AP, 11 of 144 alleles in patients with RAP, and in 19 of 1,340 control alleles. There was no difference in the prevalence of the polymorphism between sentinel attack patients and controls. Patients with the polymorphism were more prone to develop recurrent attacks (odds ratio (OR)=19.1, 95% confidence interval (CI): 2.4-149.6). CONCLUSIONS: The SPINK1 N34S polymorphism was not associated with the sentinel AP attack, but it substantially increases the risk of recurrent attacks. Additional studies are needed to further elucidate the mechanism of SPINK1-associated protection in AP.

Comparison of BISAP, Ranson's, APACHE-II, and CTSI scores in predicting organ failure, complications, and mortality in acute pancreatitis.

OBJECTIVES: Identification of patients at risk for severe disease early in the course of acute pancreatitis (AP) is an important step to guiding management and improving outcomes. A new prognostic scoring system, the bedside index for severity in AP (BISAP), has been proposed as an accurate method for early identification of patients at risk for in-hospital mortality. The aim of this study was to compare BISAP (blood urea nitrogen >25 mg/dl, impaired mental status, systemic inflammatory response syndrome (SIRS), age>60 years, and pleural effusions) with the "traditional" multifactorial scoring systems: Ranson's, Acute Physiology and Chronic Health Examination (APACHE)-II, and computed tomography severity index (CTSI) in predicting severity, pancreatic necrosis (PNec), and mortality in a prospective cohort of patients with AP. METHODS: Extensive demographic, radiographic, and laboratory data from consecutive patients with AP admitted or transferred to our institution was collected between June 2003 and September 2007. The BISAP and APACHE-II scores were calculated using data from the first 24 h from admission. Predictive accuracy of the scoring systems was measured by the area under the receiver-operating curve (AUC). RESULTS: There were 185 patients with AP (mean age 51.7, 51% males), of which 73% underwent contrast-enhanced CT scan. Forty patients developed organ failure and were classified as severe AP (SAP; 22%). Thirty-six developed PNec (19%), and 7 died (mortality 3.8%). The number of patients with a BISAP score of > or =3 was 26; Ranson's > or =3 was 47, APACHE-II > or =8 was 66, and CTSI > or =3 was 59. Of the seven patients that died, one had a BISAP score of 1, two had a score of 2, and four had a score of 3. AUCs for BISAP, Ranson's, APACHE-II, and CTSI in predicting SAP are 0.81 (confidence interval (CI) 0.74-0.87), 0.94 (CI 0.89-0.97), 0.78 (CI 0.71-0.84), and 0.84 (CI 0.76-0.89), respectively. CONCLUSIONS: We confirmed that the BISAP score is an accurate means for risk stratification in patients with AP. Its components are clinically relevant and easy to obtain. The prognostic accuracy of BISAP is similar to those of the other scoring systems. We conclude that simple scoring systems may have reached their maximal utility and novel models are needed to further improve predictive accuracy.

Elevated serum neutrophil gelatinase-associated lipocalin is an early predictor of severity and outcome in acute pancreatitis.

OBJECTIVES: About 210,000 new cases of acute pancreatitis (AP) involving reversible inflammation of the pancreas are reported in the United States every year. About one-fourth of all patients with AP go on to develop severe acute pancreatitis (SAP), which, unlike uncomplicated or mild acute pancreatitis (MAP, usually a self-limiting disease), constitutes a life-threatening condition with systemic complications, chiefly multiorgan dysfunction. An early prediction of the severity and outcome of patients with acute pancreatitis (AP) can lead to better treatment regimens for patients with SAP. There is currently no established biomarker for the early diagnosis of SAP. In this study, we investigated the potential of serum neutrophil gelatinase-associated lipocalin (NGAL) as an early marker to distinguish severe (SAP) from MAP and examine its ability to predict the prognosis of patients with SAP. METHODS: To check the time kinetics of rise in NGAL during AP, we quantified NGAL levels in sera from mice with MAP or SAP at various time points (6, 12, 24 and 48 h) using sandwich enzyme-linked immunosorbent assay. NGAL levels were also quantified in serum from 28 MAP and 16 SAP cases and compared with 28 chronic pancreatitis and 30 healthy control samples. Samples collected within 5 days from onset of symptoms were included. The relationship of NGAL levels with survival and multiorgan failure (MOF) in SAP was also examined. RESULTS: Although NGAL levels were significantly higher in mice with both MAP and SAP 6 h after induction (compared to control animals), only mice with SAP exhibited a significant increase in NGAL levels at 24 h (P=0.003). NGAL levels declined at 48 h after induction in animals with both MAP and SAP but did not reach baseline levels. Among patients, mean (+/-s.e.) serum NGAL level was significantly higher in SAP (634+/-139 ng/ml) compared to MAP (84.7+/-7 ng/ml, P=0.0001). On subanalysis, the difference between MAP and SAP cases was significant in the first 48 h but not at 72, 96, or 120 h. NGAL was 100%, 96%, 97%, and 84% specific and 100%, 87.5%, 92%, and 94% sensitive in distinguishing SAP from MAP at 48, 72, 96, and 120 h, respectively, after the onset of symptoms. NGAL levels were significantly higher in SAP cases complicated by MOF (P=0.004), and high NGAL levels in SAP appeared to correlate with a fatal outcome. CONCLUSIONS: Our data provide the first evidence for the potential of serum NGAL as an early marker to distinguish MAP from SAP. Further, high NGAL levels predict MOF and fatal outcome in patients with SAP. This study provides sufficient evidence for multi-institutional randomized trials for estimating the potential of NGAL as early biomarker for SAP.

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.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Epidermal growth factor serum levels and the 61 G/A polymorphism in patients with acute pancreatitis.

BACKGROUND: Epidermal growth factor (EGF) binds to pancreatic acinar cells and facilitates recovery from acute pancreatitis (AP). In animal models, EGF protects against pancreatic injury and prevents septic complications. The role of EGF in human AP is unknown. AIMS: The aim of this study was to assess EGF serum levels in AP patients and whether the EGF +61 G/A single nucleotide polymorphism (SNP) affects susceptibility and/or severity of AP. METHODS: Hospitalized AP patients were prospectively enrolled. Demographics, clinical features, DNA and early serum samples were collected when available. Patients were classified into mild (79%) and severe AP (21%) based on organ failure for >or=48 h. Early serum samples were quantitatively assayed for EGF levels. The EGF +61 G/A SNP was evaluated by restriction fragment length polymorphism analysis. RESULTS: There were 179 patients ascertained with AP. EGF levels were measured in a subgroup of 60 patients with early serum samples (17 severe) and in serum from 58 healthy controls. Serum EGF levels within 48 h from the onset of pain were significantly lower in AP patients (mean 13.5 pg/ml) compared to controls (25.2 pg/ml; P=0.015). Furthermore, EGF levels were significantly lower in severe patients when compared to mild (7.8 vs. 14.3 pg/ml; P=0.026). DNA from all 179 patients and 189 healthy controls was sequenced. The EGF +61 G/A SNP did not affect susceptibility to or severity of AP. CONCLUSIONS: EGF serum levels are decreased early in the course of AP and are further suppressed in severe AP. The EGF +61 G/A polymorphism has no effect on AP.

Elevated serum creatinine as a marker of pancreatic necrosis in acute pancreatitis.

OBJECTIVES: Pancreatic necrosis is a serious complication of acute pancreatitis. The identification of simple laboratory tests to detect subjects at risk of pancreatic necrosis may direct management and improve outcome. This study focuses on the association between routine laboratory tests and the development of pancreatic necrosis in patients with acute pancreatitis. METHODS: In a cohort of 185 patients with acute pancreatitis prospectively enrolled in the Severity of Acute Pancreatitis Study, patients with contrast-enhanced computerized tomography performed were selected (n=129). Serum hematocrit, creatinine, and urea nitrogen on admission and peak values within 48 h of admission were analyzed. The volume of intravenous fluid resuscitation was calculated for each patient. RESULTS: Of 129 patients, 35 (27%) had evidence of pancreatic necrosis. Receiver operating characteristic curves for pancreatic necrosis revealed an area under the curve of 0.79 for admission hematocrit, 0.77 for peak creatinine, and 0.72 for peak urea nitrogen. Binary logistic regression yielded that all three tests were significantly associated with pancreatic necrosis (P<0.0001), with the highest odds ratio, 34.5, for peak creatinine. The volume of intravenous fluid resuscitation was similar in patients with and without necrosis. Low admission hematocrit (< or =44.8%) yielded a negative predictive value of 89%; elevated peak creatinine (>1.8 mg/dl) within 48 h yielded a positive predictive value of 93%. CONCLUSIONS: We confirm that a low admission hematocrit indicates a low risk of pancreatic necrosis (PNec) in patients with acute pancreatitis. In contrast, an increase in creatinine within the first 48 h is strongly associated with the development of PNec. This finding may have important clinical implications and warrants further investigation.

Unusual Case of Life-Threatening Gastro Intestinal Bleed from a Splenic Artery Pseudoaneurysm: Case Report and Review of Literature.

Large upper gastro intestinal (GI) bleeding can be life-threatening. Splenic artery pseudoaenurysm (SAP) is rare but can cause massive upper GI bleeding. We report a case of a 57-year-old woman who had massive upper GI bleeding from SAP eroding into distal duodenum. Literature review shows SAP can bleed into stomach or pancreatic pseudocyst or biliary tree and peritoneal cavity; however, there are no previous reported cases of SAP bleeding into distal duodenum. Splenic artery embolization (SAE) is the preferred treatment for a bleeding SAP. Splenic infarcts can result following a SAE.

Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population: role of serine protease inhibitor Kazal 1type and alcohol.

AIM: To test the hypothesis that calcium sensing receptor (CASR) polymorphisms are associated with chronic pancreatitis (CP), and to determine whether serine protease inhibitor Kazal 1type (SPINK1) N34S or alcohol are necessary co-factors in its etiology. METHODS: Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms (SNPs) in exon 7 (A986S, R990G, and Q1011E). RESULTS: The CASR exon 7 R990G polymorphism was significantly associated with CP (OR, 2.01; 95% CI, 1.12-3.59; P = 0.015). The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption (OR, 3.12; 95% CI, 1.14-9.13; P = 0.018). There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected. CONCLUSION: Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption.

Recurrent Acute Pancreatitis: International State-of-the-Science Conference With Recommendations.

Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research. After a vetting process, these topics were assigned to a group of experts from around the world with special interest in RAP. Data were presented as part of a workshop on RAP organized as a part of the annual meeting of the America Pancreatic Association. Pretest and Posttest questions were administered, and the responses were tabulated by the current Grades of Recommendation Assessment, Development and Evaluation system. The consensus guidelines were established in the format of a diagnostic algorithm. Several deficiencies were identified with respect to data on etiology, treatment efficacies, and areas that need immediate research.