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IntroductionDespite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency.MethodsAn online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years.ResultsOverall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency.ConclusionThis survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence. Introduction: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. Methods: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. Results: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. Conclusion: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

Background and aims Ionizing radiation exposure during endoscopic retrograde cholangiopancreatography (ERCP) is an important quality issue especially in children. We aim to identify factors associated with extended fluoroscopy time (FT) in children undergoing ERCP. Methods ERCP on children ≤18 years from 15 centers were entered prospectively into a REDCap database from 5/2014 until 5/2018. Data were retrospectively evaluated for outcome and quality measures. A univariate and step-wise linear regression analysis was performed to identify factors associated with increased FT. Results 1073 ERCPs performed in 816 unique patients met inclusion criteria. Median age was 12.2 years (IQR 9.3-15.8). 767 (71%) patients had native papillae. The median FT was 120 seconds (IQR 60-240). Factors associated with increased FT included procedures performed on patients with chronic pancreatitis, ERCPs with ASGE difficulty grade ≥3, ERCPs performed by Pediatric Gastroenterologist (GI) with Adult GI supervision, and ERCPs performed at non-free standing children's hospitals. Hispanic ethnicity was the only factor associated with lower FT. Conclusion Several factors were associated with prolonged FTs in pediatric ERCP that differed from adult studies. This underscores that adult quality indicators cannot always be translated to pediatric patients. This data can better identify children with higher risk for radiation exposure and improve quality outcomes during pediatric ERCP. An infographic is available for this article at:http://links.lww.com/MPG/C570.

Objectives Adults with chronic pancreatitis (CP) have a high risk for developing pancreatogenic diabetes mellitus (DM), but little is known regarding potential risk factors for DM in children with acute recurrent pancreatitis (ARP) or CP. We compared demographic and clinical features of children with ARP or CP, with and without DM, in the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE) registry. Methods We reviewed the INSPPIRE database for the presence or absence of physician-diagnosed DM in 397 children, excluding those with total pancreatectomy with islet autotransplantation, enrolled from August 2012 to August 2017. Patient demographics, BMI percentile, age at disease onset, disease risk factors, disease burden, and treatments were compared between children with DM (n = 24) and without DM (n = 373). Results Twenty-four children (6% of the cohort) had a diagnosis of DM. Five of 13 tested were positive for beta cell autoantibodies. The DM group was 4.2 years [95% confidence interval (CI) 3-5.4] older at first episode of acute pancreatitis, and tended to more often have hypertriglyceridemia [odds ratio (OR) 5.21 (1.33-17.05)], coexisting autoimmune disease [OR 3.94 (0.88-13.65)] or pancreatic atrophy [OR 3.64 (1.13, 11.59)]. Conclusion Pancreatic atrophy may be more common among children with DM, suggesting more advanced exocrine disease. However, data in this exploratory cohort also suggest increased autoimmunity and hypertriglyceridemia in children with DM, suggesting that risk factors for type 1 and type 2 DM, respectively may play a role in mediating DM development in children with pancreatitis.

ObjectiveThe aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites.Study designData were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson chi-square test. Differences in disease burden were compared by Kruskal-Wallis test.ResultsOut of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (P

We created the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE 2) cohort to study the risk factors, natural history, and outcomes of pediatric acute recurrent pancreatitis and chronic pancreatitis (CP). Patient and physician questionnaires collect information on demographics, clinical history, family and social history, and disease outcomes. Health-related quality of life, depression, and anxiety are measured using validated questionnaires. Information entered on paper questionnaires is transferred into a database managed by Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer's Coordinating and Data Management Center. Biosamples are collected for DNA isolation and analysis of most common pancreatitis-associated genes.Twenty-two sites (18 in the United States, 2 in Canada, and 1 each in Israel and Australia) are participating in the INSPPIRE 2 study. These sites have enrolled 211 subjects into the INSPPIRE 2 database toward our goal to recruit more than 800 patients in 2 years. The INSPPIRE 2 cohort study is an extension of the INSPPIRE cohort study with a larger and more diverse patient population. Our goals have expanded to include evaluating risk factors for CP, its sequelae, and psychosocial factors associated with pediatric acute recurrent pancreatitis and CP.

Background The etiology of primary sclerosing cholangitis (PSC) is unknown. PSC and Cystic Fibrosis related liver disease have common features: chronic inflammation, biliary damage and similar cholangiographic findings. It is unknown whether or not PSC is related to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. We hypothesize that a sub-group of PSC patients may be a “single-organ” presentation of CF. Methods Patients with PSC underwent nasal potential difference (NPD) measurement, sweat chloride measurement and complete CFTR sequencing by new generation sequencing. Results 6/32 patients aged 46 ± 13 yrs. had CFTR causing mutations on one allele and 19 had CFTR polymorphisms; 6/23 tested had abnormal and 21 had intermediate sweat tests; 4/32 patients had abnormal NPD. One patient had chronic pancreatitis and was infertile. Conclusions 19% of PSC patients had features of CFTR related disorder, 19% carry CFTR mutations and 50% had CFTR polymorphisms. In some patients, PSC may be a single organ presentation of CF or a CFTR-related disorder.

OBJECTIVES:Autoimmune pancreatitis (AIP) represents a complex immune-mediated pancreas disorder. Pediatric AIP (P-AIP) is rare. We have recently summarized the characteristic features of P-AIP. We now aim to develop recommendation statements to standardize the diagnostic and therapeutic approach to P-AIP and facilitate future research in the field. METHODS:A panel of pediatric gastroenterologists participating in the International Study Group of Pediatric Pancreatitis: In search for a cuRE was formed to discuss and then vote on 15 recommendation statements. A consensus of at least 80% was obtained following 3 voting rounds and revision of the statements. RESULTS:We have now generated 15 statements to help standardize the approach to diagnosis and management of P-AIP. CONCLUSIONS:The first P-AIP recommendation statements developed by the International Study Group of Pediatric Pancreatitis: In search for a cuRE group are intended to bring standardization to the diagnosis and treatment of this rare childhood disorder. These statements may help guide a uniform approach to patient care and facilitate future research studies.

Background Temporary fecal diversion by means of an ileostomy or colostomy has been used in the surgical management of refractory colonic and perianal Crohn disease (CD). The aims of our study were to evaluate the outcomes after fecal diversion in pediatric patients with colonic and perianal CD. Methods The records of patients who underwent fecal diversion for colonic and perianal CD at Children's Hospital of Wisconsin between July 2000 and June 2014 were reviewed retrospectively. Patient demographics, medication use, onset and extent of disease, response to fecal diversion, rate of stoma reversal and relapse rate after stoma reversal were recorded. Results We identified 28 consecutive patients (20 females, 8 males; median age 13.9years) undergoing fecal diversion for refractory colonic (n=21) and perianal CD (n=7). Median duration of follow-up after fecal diversion was 2.26years (range, 0.79–10.2years). The response to fecal diversion was sustained clinical remission in 13/28 (46%), temporary clinical remission in 10/28 (36%), no change in 5/28 (18%). Intestinal continuity was restored in 14/28 (50%) patients; however, 3 (21%) required permanent stoma after reconnection. Classification tree analysis identified that female patients without perianal CD had higher rates of stoma reversal (p=0.008). Conclusions Fecal diversion can induce remission in pediatric patients with refractory colonic and perianal CD. Restoration of intestinal continuity was achieved in about 39%. Female patients without perianal CD carried no risk of a permanent stoma. Level of evidence Level III study.

Background Inflammatory bowel diseases (IBD) often begins early in life. Adolescents and young adults (AYA) with IBD have to acquire behaviors that support self-care, effective healthcare decision-making, and self-advocacy to successfully transition from pediatric to adult health care. Despite the importance of this critical time period, limited empirical study of factors associated with transition readiness in AYA exists. This study aimed to describe transition readiness in a sample of AYA with IBD and identify associated modifiable and nonmodifiable factors. Methods Seventy-five AYA (ages 16-20) and their parents participated. AYA and parents reported on demographics, patient-provider transition-related communication, and transition readiness. AYA self-reported on disease self-efficacy. Disease information was abstracted from the medical record. Results Deficits in AYA responsibility were found in knowledge of insurance coverage, scheduling appointments, and ordering medication refills. Older AYA age, higher AYA disease-management self-efficacy, and increased patient-provider transition communication were each associated with higher overall transition readiness and AYA responsibility scores. Regression analyses revealed that older AYA age and increased patient-provider transition-related communication were the most salient predictors of AYA responsibility for disease management and overall transition readiness across parent and AYA reports. Conclusions AYA with IBD show deficits in responsibility for their disease management that have the potential to affect their self-management skills. Findings suggest provider communication is particularly important in promoting transition readiness. Additionally, it may be beneficial to wait to transition patients until they are older to allow them more time to master skills necessary to responsibly manage their own healthcare.

Background:Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed.Methods:The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pan

ObjectivesAcute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) have been diagnosed in children at increasing rates during the past decade. As pediatric ARP and CP are still relatively rare conditions, little quality evidence is available on which to base the diagnosis and determination of etiology. The aim of the study was to review the current state of the literature regarding the etiology of these disorders and to developed a consensus among a panel of clinically active specialists caring for children with these disorders to help guide the diagnostic evaluation and identify areas most in need of future research.MethodsA systematic review of the literature was performed and scored for quality, followed by consensus statements developed and scored by each individual in the group for level of agreement and strength of the supporting data using a modified Delphi method. Scores were analyzed for the level of consensus achieved by the group.ResultsThe panel reached consensus on 27 statements covering the definitions of pediatric ARP and CP, evaluation for potential etiologies of these disorders, and long-term monitoring. Statements for which the group reached consensus to make no recommendation or could not reach consensus are discussed.ConclusionsThis consensus helps define the minimal diagnostic evaluation and monitoring of children with ARP and CP. Even in areas in which we reached consensus, the quality of the evidence is weak, highlighting the need for further research. Improved understanding of the underlying cause will facilitate treatment development and targeting.

ObjectivesThe aim of the study was to understand the association of frequent opioid use with disease phenotype and pain pattern and burden in children and adolescents with acute recurrent (ARP) or chronic pancreatitis (CP).MethodsCross-sectional study of children

ObjectiveThe aim of the study was to determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors.Study designData were collected from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) cohort. Kaplan-Meier curves were constructed to calculate duration of progression from initial attack of acute pancreatitis (AP) to CP. Log-rank test was used to compare survival (nonprogression) probability distribution between groups. Cox proportional hazard regression models were fitted to obtain hazard ratio (with 95% confidence interval [CI]) of progression for each risk variable.ResultsOf 442 children, 251 had ARP and 191 had CP. The median time of progression from initial attack of AP to CP was 3.79 years. The progression was faster in those ages 6 years or older at the first episode of AP compared to those younger than 6 years (median time to CP: 2.91 vs 4.92 years; P = 0.01). Children with pathogenic PRSS1 variants progressed more rapidly to CP compared to children without PRSS1 variants (median time to CP: 2.52 vs 4.48 years; P = 0.003). Within 6 years after the initial AP attack, cumulative proportion with exocrine pancreatic insufficiency was 18.0% (95% CI: 12.4%, 25.6%); diabetes mellitus was 7.7% (95% CI: 4.2%, 14.1%).ConclusionsChildren with ARP rapidly progress to CP, exocrine pancreatic insufficiency, and diabetes. The progression to CP is faster in children who were 6 years or older at the first episode of AP or with pathogenic PRSS1 variants. The factors that affect the aggressive disease course in childhood warrant further investigation.

ObjectivesThe aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared.MethodsDemographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.ResultsAlcohol was a risk in 53% of adults and 1% of children (P

Objectives: Jejunal tube feeding (JTF) is increasingly becoming the standard of care for children in whom gastric tube feeding is insufficient to achieve caloric needs. Given a lack of a systematic approach to the care of JTF in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimize its utility and safety. Methods: A group of members of the Gastroenterology and Nutrition Committees of the European Society of Paediatric Gastroenterology Hepatology and Nutrition and of invited experts in the field was formed in September 2016 to produce this clinical guide. Seventeen clinical questions treating indications and contraindications, investigations before placement, techniques of placement, suitable feeds and feeding regimen, weaning from JTF, complications, long-term care, and ethical considerations were addressed. A systematic literature search was performed from 1982 to November 2018 using PubMed, the MEDLINE, and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalized. In the absence of evidence from randomized controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 33 recommendations were voted on using the nominal voting technique. Conclusions: JTF is a safe and effective means of enteral feeding when gastric feeding is insufficient to meet caloric needs or is not possible. The decision to place a jejunal tube has to be made by close cooperation of a multidisciplinary team providing active follow-up and care.

Background & Aims Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. Methods We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. Results Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39–5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26–4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05–4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04–1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. Conclusions Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients—factors associated with success differ from those of adult patients.

The aims of this retrospective cohort study were to classify the severity of patients admitted to the pediatric intensive care unit (PICU) with acute pancreatitis (AP) and to identify how many patients received appropriate nutritional management in accordance with more recent guidelines and the outcomes of those patients. Of the 54 children with AP, 12 (22.2%) had a primary diagnosis of AP (50% severe, 17% moderate) whereas 42 (77.8%) had a secondary diagnosis of AP (81% severe, 11.9% moderate). Just under half of the patients (48.1%) had enteral nutrition commenced before the third day of admission (50% with primary AP, 47.6% with secondary AP). The average time to initiation of enteral feeds was 2.3 days for those that received enteral nutrition. 51.8% of patients received parenteral nutrition (25% with primary AP, 59.5% with secondary AP). Most patients received enteral nutrition late and parenteral nutrition was overused in patients with AP admitted to the PICU.

ObjectiveThe aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP).MethodsWe determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations.ResultsOf 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups.ConclusionsObesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study.

IntroductionThe significance of pancreas divisum (PD) as a risk factor for pancreatitis is controversial. We analyzed the characteristics of children with PD associated with acute recurrent or chronic pancreatitis to better understand its impact.Patients and methodsWe compared children with or without PD in the well-phenotyped INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables, Pearson χ or Fisher exact test for categorical variables.ResultsPD was found in 52 of 359 (14.5%) subjects, a higher prevalence than the general population (∼7%). Females more commonly had PD (71% vs. 55%; P=0.02). Children with PD did not have a higher incidence of mutations in SPINK1, CFTR, CTRC compared with children with no PD. Children with PD were less likely to have PRSS1 mutations (10% vs. 34%; P

Objectives: Wide variations exist in how physicians manage the nutritional aspects of children affected by acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic (CP) pancreatitis. Better consensus for optimal management is needed. Methods: This consensus statement on nutrition in pediatric pancreatic diseases was developed through a joint ESPGHAN-NASPGHAN working group that performed an evidence-based search of the literature on nutrition in AP, ARP, and CP with a focus on pediatrics. The literature was summarized, quality of evidence reviewed, and expert recommendations developed. The authorship met to discuss the evidence and statements. Voting on recommendations occurred over 2 rounds based on feedback. A consensus of at least 75% was required to approve a recommendation. Areas requiring further research were identified. Results and Discussion: The literature on nutrition in pediatric pancreatitis is limited. Children with mild AP benefit from starting an early nutritional regimen in the course of the attack. Early nutrition should be attempted in severe AP when possible; enteral nutrition is preferred over parenteral nutrition. Children with ARP are likely to tolerate and benefit from a regular diet. Children with CP need ongoing assessment for growth and nutritional deficiencies, exocrine and endocrine insufficiencies. Conclusions: This document presents the first authoritative recommendations on nutritional considerations in pediatric pancreatitis. Future research should address the gaps in knowledge particularly relating to optimal nutrition for AP in children, role of diet or dietary supplements on recurrent attacks of pancreatitis and pain episodes, monitoring practices to detect early growth and nutritional deficiencies in CP and identifying risk factors that predispose children to these deficiencies.

Objective To examine longitudinal trajectories of oral thiopurine adherence over a 180-day interval in a sample of youth with inflammatory bowel disease (IBD) and to identify the role of disease activity, length of time since diagnosis, and regimen complexity in predicting adherence trajectory class membership. Method Participants included 96 adolescents (M age = 14.32 years) with IBD. Oral medication adherence was assessed via MEMS Track Caps (i.e., an electronic monitor that allows for real-time assessment of adherence) for 6 months, after which time devices were collected and data were downloaded. Medical record reviews provided information about participants' disease activity, length of time since diagnosis, and regimen complexity (including both medications and supplements) at the time of study enrollment. Results Two distinct adherence trajectory classes emerged: Group 1 represented those with consistently near-perfect adherence, whereas Group 2 represented those with mild nonadherence that increased with time. Complexity of medication regimen emerged as the only predictor of trajectory class, with adolescents whose regimen involved more than 1 daily medication administration time being more likely to be classified in Group 2 (i.e., the consistently near-perfect adherence group) than those whose regimen involved only 1 daily medication administration time. Conclusions Distinct classes of adherence trajectories in pediatric IBD can be identified with longitudinal data collection approaches; however, disease and regimen factors offered limited value in predicting adherence trajectory class. Future research should utilize longitudinal conceptualizations of adherence and examine alternative predictors of declining adherence over time.

ObjectivesAutoimmune pancreatitis (AIP) is an increasingly recognized disease entity, but data in children are limited. AIP presentation and outcome in children might differ from the adult experience. We aim to determine the characteristic features of AIP in children.MethodsData about clinical symptoms, imaging, histology, and treatment were collected using two sources: (i) a systematic literature search and (ii) the INSPPIRE database, the largest international multicenter study of pancreatitis in children and the Cliniques Universitaires St-Luc (CUSL) registry.ResultsWe identified 48 AIP cases: 30 from literature review, 14 from INSPPIRE, and 4 from CUSL. The median age at diagnosis was 13 years (range 2-17 years). Abdominal pain (43/47, 91%) and/or obstructive jaundice (20/47, 42%) were the most common symptoms at diagnosis. Elevated serum IgG4 levels were only observed in 9/40 (22%) children. Cross-sectional imaging studies were abnormal in all children including hypointense global or focal gland enlargement (39/47, 83%), main pancreatic duct irregularity (30/47, 64%), and common bile duct stricture (26/47, 55%). A combination of lymphoplasmacytic inflammation, pancreatic fibrosis, and ductal granulocyte infiltration were the main histological findings (18/25, 72%). Children with AIP had a prompt clinical response to steroids. Complications of AIP included failure of exocrine (4/25, 16%) and endocrine (3/27, 11%) pancreas function.ConclusionsPediatric AIP has a distinct presentation with features similar to type 2 AIP in adults. This comprehensive report on the largest group of children with AIP to date is expected to help with the diagnosis and management of this disease and pave the way for future research studies.

ObjectiveThe aim of this study was to characterize utilization and benefit of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP).MethodsFrom August 2012 to February 2015, 301 children with ARP or CP were enrolled in the INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) study. Physicians reported utilization and benefit of therapeutic ERCP at enrollment. Differences were analyzed using appropriate statistical methods.ResultsOne hundred seventeen children (38.9%) underwent at least 1 therapeutic ERCP. The procedure was more commonly performed in children with CP compared with those with ARP (65.8% vs 13.5%, P < 0.0001). Utility of therapeutic ERCP was reported to be similar between ARP and CP (53% vs 56%, P = 0.81) and was found to be helpful for at least 1 indication in both groups (53/99 patients [53.5%]). Predictors for undergoing therapeutic ERCP were presence of obstructive factors in ARP and CP, Hispanic ethnicity, or white race in CP.ConclusionsTherapeutic ERCP is frequently utilized in children with ARP or CP and may offer benefit in selected cases, specifically if ductal obstruction is present. Longitudinal studies are needed to clarify the efficacy of therapeutic ERCP and to explore subgroups that might have increased benefit from such intervention.

Acute pancreatitis (AP) is an emerging problem in pediatrics, with most cases resolving spontaneously. Approximately 10% to 30%, however, are believed to develop "severe acute pancreatitis" (SAP).This consensus statement on the classification of AP in pediatrics was developed through a working group that performed an evidence-based search for classification of AP in adult pancreatitis, definitions and criteria of systemic inflammatory response syndrome, and organ failure in pediatrics.Severity in pediatric AP is classified as mild, moderately severe, or severe. Mild AP is defined by AP without organ failure, local or systemic complications, and usually resolves in the first week. Moderately SAP is defined by the presence of transient organ failure that resolves in no48 hours, or local complications or exacerbation of co-morbid disease. SAP is defined by persistent organ failure that lasts48 hours. The presence of systemic inflammatory response syndrome is associated with increased risk for persistent organ dysfunction. Criteria to define organ failure must be pediatric- and age-based.Classifying AP in pediatrics in a uniform fashion will help define outcomes and encourage the development of future studies in the field of pediatric pancreatitis.

The aims of the study were to describe infliximab adherence in a pediatric inflammatory bowel disease cohort, to identify demographic and disease factors associated with adherence, and to examine differences in acute care use among adherent and nonadherent patients. Charts of patients who received infliximab at the Children's Hospital of Wisconsin (CHW) between October 2010 and October 2012 were retrospectively reviewed. A total of 151 patients met the inclusion criteria; 91.4% of the patients were adherent. Nonadherent patients had more emergency room visits and hospitalizations than adherent patients. The study is the first to show high adherence rates to infliximab in a pediatric cohort.

ImportancePediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood.ObjectiveTo characterize and identify risk factors associated with ARP and CP in childhood.Design, setting, and participantsA multinational cross-sectional study of children with ARP or CP at the time of enrollment to the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) study at participant institutions of the INSPPIRE Consortium. From August 22, 2012, to February 8, 2015, 155 children with ARP and 146 with CP (aged ≤19 years) were enrolled. Their demographic and clinical information was entered into the REDCap (Research Electronic Data Capture) database at the 15 centers. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables and Pearson χ2 test or Fisher exact test for categorical variables. Disease burden variables (pain variables, hospital/emergency department visits, missed school days) were compared using Wilcoxon rank sum test.Main outcomes and measuresDemographic characteristics, risk factors, abdominal pain, and disease burden.ResultsA total of 301 children were enrolled (mean [SD] age, 11.9 [4.5] years; 172 [57%] female); 155 had ARP and 146 had CP. The majority of children with CP (123 of 146 [84%]) reported prior recurrent episodes of acute pancreatitis. Sex distribution was similar between the groups (57% female in both). Hispanic children were less likely to have CP than ARP (17% vs 28%, respectively; odds ratio [OR] = 0.51; 95% CI, 0.29-0.92; P = .02). At least 1 gene mutation in pancreatitis-related genes was found in 48% of patients with ARP vs 73% of patients with CP (P

Objective To estimate selected direct medical care costs of children with chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). Methods We performed a cross-sectional study of data from International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE), a multinational registry of children with ARP or CP. We determined health care utilization and estimated costs of hospitalizations, surgical and endoscopic procedures, and medications in our study population. Health care utilization data were obtained from all subjects enrolled in the study, and costs were calculated using national United States costs. Results We included 224 subjects (median age 12.7 years), 42% of whom had CP. Mean number of hospitalizations, including for surgery and endoscopic retrograde cholangiopancreatography, was 2.3 per person per year, costing an estimated average $38,755 per person per year. Including outpatient medications, estimated total mean cost was $40,589 per person per year. Subjects using surgical procedures or endoscopic retrograde cholangiopancreatography incurred mean annual costs of $42,951 per person and $12,035 per person, respectively. Estimated annual costs of pancreatic enzyme replacement therapy, diabetic medications, and pain medications were $4114, $1761, and $614 per person, respectively. In an exploratory analysis, patients with the following characteristics appear to accrue higher costs than those without them: more frequent ARP attacks per year, reported constant or episodic pain, family history of pancreatic cancer, and use of pain medication. Conclusions ARP and CP are uncommon childhood conditions. The severe burden of disease associated with these conditions and their chronicity results in high health care utilization and costs. Interventions that reduce the need for hospitalization could lower costs for these children and their families.

Background: To examine the validity of patient self-report of thiopurine adherence in pediatric inflammatory bowel disease (IBD) against an objective electronic monitoring adherence measure, and to investigate the role of youth and maternal involvement in remembering to take daily medications as predictors of medication adherence. Methods: Fifty-one youths with IBD, ages 11–18 years, participated. Youths completed questionnaire assessments of their own and their maternal caregiver's involvement in remembering to take daily medications at baseline, completed monthly interviews assessing thiopurine adherence over the past week for a period of 6 months, and utilized a Medication Events Monitoring System (MEMS) electronic monitor for their thiopurine medication for 6 months. Participants were grouped into adherent (at least 80% of doses taken based on objective MEMS caps) or nonadherent for analyses. Results: Youths who were nonadherent based on electronic monitoring overestimated their adherence by 23%, whereas adherent youths overestimated their adherence by only 2%, and as such patient self-report offered little utility in identifying youths who were nonadherent. Youths who reported high levels of involvement in remembering to take their medications were nearly eight times less likely to be nonadherent. Conclusions: The current findings provide evidence that clinicians who work with children and adolescents with IBD may benefit from modifying their approach to nonadherence screening. Asking about youth involvement in remembering daily medications may be more informative than asking them to recall their medication-taking behavior over the last week in identifying those at highest risk for nonadherence. (Inflamm Bowel Dis 2011;)

OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.

Acute pancreatitis is a painful inflammatory disorder with a major health impact (1,2). It accounts for more than 230,000 adult hospitalizations annually in the United States at an estimated cost of $4.6 to 4.8 billion/year (3). Even mild disease may require analgesia, nutritional support, and hospital stay ranging from 3 to 10 days (4). Data in children with acute pancreatitis are limited, but they suggest important differences vis-a-vis adults (1,5). Although alcohol and biliary tract disease cause most cases in adults, etiologies in children are more variable. Adult pancreatitis has been increasing in the last 4 decades (6). This has been attributed to the increasing incidence of gallstone pancreatitis. In children, recent reports indicate an increase of acute pancreatitis within the last decade (7–9). However, these data are confined to limited series from specific geographic locations. It is unclear whether the increase is attributable to local factors or a general shift in the epidemiology of this disease. Our primary objective was to analyze the frequency of pediatric pancreatitis in the last 12 years at Yale-New Haven Children’s Hospital. Our secondary objective was to perform detailed analysis on etiologies of pancreatitis in children. If changes in frequency were present, then we sought to attribute causes for observed trends by analyzing shifts in etiologies, body mass index (BMI), or referral patterns during the study period.

SUMMARY Five cases of Sandifer syndrome are reported, and the authors suggest that frequently the diagnosis may be overlooked, especially when the patient has a milder or incomplete form of the syndrome. None of the children had hiatal hernia, so this is not an essential requirement for the syndrome. The findings in these five cases suggest that the abnormal posturing associated with this syndrome may be the result of extreme sensitivity of the esophagus to refluxed gastric acid. RESUME Le syndrome de Sandifer: une entile clinique depreciee Cinq cas de syndrome de Sandifer sont rapportes et les auteurs suggerent que le diagnostic peut etre souvent neglige, specialement quand le malade presente une forme legere ou incomplete du syndrome. Aucun des enfants n'avaient de hernie hiatale et celle-ci n'est done pas une manifestation essentielle du syndrome. Les donnees des cinq cas suggerent que les postures anormales associees au syndrome peuvent etre le resultat de l'extreme sensibilite de l'oesophage au reflux d'acide gastrique. ZUSAMMENFASSUNG Sandifer Syndrom: ein wenig beachtetes klinisches Bild Es wird uber funf Falle mit einem Sandifer Syndrom berichtet. Die Autoren sind der Ansicht, daB die Diagnose vermutlich haufig nicht gestellt wird, besonders dann, wenn der Patient eine mildere oder inkomplette Form des Syndroms aufweist. Keines der Kinder hatte eine Hiatushernie, diese ist also fur das Syndrom nicht ausschlaggebend. Die Befunde dieser fiinf Falle lassen vermuten, das die Fehlhaltung, die bei diesem Syndrom auftritt, moglicherweise mit der starken Empfindlichkeit des Oesophagus gegen die aufsteigende Magensaure zusammenhangt. RESUMEN Sindrome de Sandifer: una entidad clinica no apreciada Se aportan cinco casos de sindrome de Sandifer y los autores sugieren que con frecuencia el diagnostico puede ser pasado por alto, especialmente cuando el paciente tiene una forma menor o incompleta del sindrome. Ninguno de los nifios tenia una hernia de hiato, por lo que este no es un requisito esencial para el sindrome. Los hallazgos en los cinco casos sugieren que la anomalia postural asociada con este sindrome puede ser el resultado de un a extrema sensibilidad del esofago al reflujo acido gastrico.

Objective: To evaluate the utility of magnetic resonance cholangiopancreatography (MRCP) in children and to compare MRCP with direct cholangiopancreatography (CP). Materials and Methods: We performed an unblinded, retrospective chart review of 32 children (ages 0–18 years, 17 male) who underwent MRCP between January 2002 and June 2005. MRCP, endoscopic retrograde cholangiopancreatography (ERCP), percutaneous fluoroscopic or intraoperative studies of the pancreatobiliary tree, and clinical outcomes were evaluated. Results: Seventeen (52%) children had MRCP alone, 15 (48%) had both MR and direct CP. MRCP results correlated with other evaluative methods in 14/15 (93%) cases. There was 1 false positive (anomalous pancreatic duct union) and 0 false negatives for anatomic abnormalities. Therapeutic intervention was performed in 7 of 28 children initially evaluated by MRCP (2 sphincter of Oddi dysfunction, 2 choledocholithiasis, 2 primary sclerosing cholangitis, 1 congenital hepatic cysts) and 1 of 4 children initially evaluated by ERCP (primary sclerosing cholangitis). All 17 children initially evaluated by MRCP had no change in clinical status to suggest a missed anatomic lesion or therapeutic opportunity. Conclusions: In this retrospective study, MRCP was sensitive and specific in identifying anatomic abnormalities of the pancreatobiliary tree in children. MRCP should be considered before direct CP to evaluate anatomic abnormalities of the pancreatobiliary tree.

Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive method to evaluate a wide variety of pancreatobiliary disorders. These disorders include choledochal cyst, cholelithiasis, choledocholithiasis, biliary atresia, Caroli's disease, primary sclerosing cholangitis, disorders of the pancreatobiliary junction, pancreas divisum, and pancreatic duct abnormalities related to chronic pancreatitis. The use of MRCP in children is increasing as experience with MRCP grows, and its technological accuracy rivals that of endoscopic evaluation. We review the current state of MRCP use in children.

The aim of this study is to describe the demographics and outcomes of children with a discharge diagnosis of acute pancreatitis (AP) from the pediatric intensive care unit (PICU).Data for this retrospective cohort study were obtained from a multisite, clinical PICU database. PICU discharges with a primary or secondary diagnosis of AP (SAP) between 2009 and 2013 from 113 centers were reviewed. We also obtained the Pediatric Index of Mortality 2 Risk of Mortality (PIM2ROM), an indicator of the severity of illness.Of 360,162 PICU discharges, 2026 with a diagnosis of AP were analyzed further (0.56%)-331 had a primary diagnosis of AP, whereas 1695 had a SAP. Among children with primary AP, median PIM2ROM was 1.0% (interquartile range [IQR] 0.8%-1.4%). Fifty-five children with primary AP (16.6%) required mechanical ventilation (MV) for a median of 3.8 days (IQR 1.0-9.3). The length of stay (LOS) in PICU was a median of 2.95 days (IQR 1.53-5.90). Only 1 patient died (mortality 0.3%). Among children with secondary AP, median PIM2ROM was 1.1% (IQR 0.8%-4.0%). A total of 711 children (42.0%) with secondary AP required MV for a median of 5.8 days (IQR 1.8-14.0). PICU LOS was a median of 4.43 days (IQR 1.84-11.22). There were 115 deaths in this group (mortality 6.8%). Median PIM2ROM, PICU LOS, mortality (all P 0.001), and length of MV (P = 0.035) were significantly greater in children with secondary AP than with primary AP.Unlike in adult series, children with AP rarely die. Patients with secondary AP experience more morbidity and mortality than patients with primary AP.

OBJECTIVE. Our goal was to characterize valproic acid–associated pancreatitis in children.PATIENTS AND METHODS. The charts of all patients with pancreatitis (diagnosed by using strict criteria) associated with valproic acid during a 10-year period were reviewed. Clinical and laboratory results were abstracted.RESULTS. Twenty-two patients with valproic acid–associated pancreatitis were seen during the study period. Symptoms were similar to those of patients with pancreatitis from other etiologies and included abdominal pain/tenderness (83%), vomiting/retching (74%), abdominal distention (30%), and fever/chills (26%). Valproic acid levels were in the therapeutic range in all but 1 patient. The mean duration of therapy before the onset of pancreatitis was 32 months. The serum lipase level was >3 times the reference value in all patients, but the serum amylase level was not significantly elevated in 31% of the patients tested. Imaging studies altered clinical management in only 1 patient. The length of stay was generally brief (mean: 8 days). Two patients died. Of the 5 patients who were rechallenged, 4 had relapses.CONCLUSIONS. Valproic acid–associated pancreatitis does not depend on valproic acid serum level and may occur any time after the onset of therapy. The serum lipase level is more sensitive than the serum amylase level and should be obtained when pancreatitis is suspected. Early imaging studies did not change clinical management. Rechallenge with valproic acid is dangerous and should be avoided.