Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis

OBJECTIVE: The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). METHODS: We 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. RESULTS: Of 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. CONCLUSIONS: Obesity 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

Chronic pancreatitis: Pediatric and adult cohorts show similarities in disease progress despite different risk factors

Objectives: 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. Methods: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1,063 adults were compared using appropriate statistical tests for categorical and continuous variables. Results: Alcohol was a risk in 53% of adults and 1% of children (p<0.0001); tobacco in 50% of adults and 7% of children (p<0.0001). Obstructive factors were more common in children (29% vs 19% in adults, p=0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, p=0.107). Diabetes was more common in adults than children (36% vs 4% respectively, p<0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared to INSPPIRE subjects. These two cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, p=0.011). Conclusions: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP

Risk Factors for Rapid Progression From Acute Recurrent to Chronic Pancreatitis in Children: Report From INSPPIRE

Objective To determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors. Study Design Data 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 (non-progression) probability distribution between groups. Cox proportional hazard regression models were fitted to obtain hazard ratio (with 95% CI) of progression for each risk variable. Results Of 442 children, 251 had ARP, 191 CP. The median time of progression from initial attack of AP to CP was 3.79 years. The progression was faster in those age ≥6 years at the first episode of AP compared to those age <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 six years after the initial AP attack, cumulative proportion with exocrine pancreatic insufficiency (EPI) was 18.0% (95% CI: 12.4%, 25.6%); diabetes mellitus was 7.7% (95% CI: 4.2%, 14.1%). Conclusions Children with ARP rapidly progress to CP, EPI and diabetes. The progression to CP is faster in children who were ≥6 years at the first episode of AP or with pathogenic PRSS1 variants. The factors that impact the aggressive disease course in childhood warrant further investigation

Interobserver Agreement for CT and MRI Findings of Chronic Pancreatitis in Children: A Multicenter Ancillary Study Under the INSPPIRE Consortium

Background: Imaging findings represent key criteria for diagnosing chronic pancreatitis in children. Understanding radiologists’ agreement for imaging findings is critical to standardizing and optimizing diagnostic criteria. Objective: To evaluate the interobserver agreement among experienced pediatric radiologists for subjective, quantitative, and semi-quantitative imaging findings of chronic pancreatitis in children. Methods: In this retrospective study, CT or MRI examinations performed in children with chronic pancreatitis were submitted by six sites participating in the INSPPIRE consortium. One pediatric radiologist from each of the six sites reviewed examinations; three of the radiologists independently reviewed all CT examinations, and the other three radiologists independently reviewed all MRI examinations. Reviewers recorded 13 categorical imaging findings of chronic pancreatitis and measured pancreas thickness and duct diameter. Agreement was assessed using kappa coefficients for the categorical variables and intraclass correlation coefficients (ICC) for the continuous measures. Results: A total of 76 CT and 80 MRI examinations performed in 110 children (mean age, 11.3±4.6 years; 65 girls, 45 boys) were reviewed. For CT, kappa coefficients for categorical findings ranged from −0.01 to 0.81, with relatively high kappa coefficients for parenchymal calcification (κ=0.81), main pancreatic duct dilation (κ=0.63), and atrophy (κ=0.52). ICCs for parenchymal thickness measurements ranged from 0.57 in the pancreas head to 0.80 in the body and tail. ICC for duct diameter was 0.85. For MRI, kappa coefficients for categorical findings ranged from −0.01 to 0.74, with relatively high kappa coefficients for main duct irregularity (κ=0.74), side branch dilation (κ=0.70), number of dilated side branches (κ=0.65), and main duct dilation (κ=0.64); kappa coefficient for atrophy was 0.52. ICCs for parenchymal thickness measurements ranged from 0.59 in the pancreas head to 0.68 in the tail. ICC for duct diameter was 0.77. Conclusion: Interobserver agreement was fair to moderate for most CT and MRI findings of chronic pancreatitis in children. Clinical Impact: This study highlights challenges for the imaging diagnosis of pediatric chronic pancreatitis. Standardized and/or objective criteria are needed given the importance of imaging in diagnosis

Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children with Acute Recurrent or Chronic Pancreatitis

Objectives: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Methods: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. Results: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. Conclusions: Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP

Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis

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

Health-Related Quality of Life in Pediatric Acute Recurrent or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors

ObjectivesAbdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL.MethodsData were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment.ResultsThe sample included 368 children (54.3% girls, mean age = 12.7years, standard deviation [SD] = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B = -10.28, P  &lt; 0.001), episodic and constant abdominal pain (B = 04.66, P = 0.03; B = -13.25, P &lt; 0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271] = 8.34, P &lt; 0.001). Borderline and clinical levels of emotional and behavioral problems (B = -10.18, P &lt; 0.001; B = -15.98, P &lt; 0.001), and constant pain (B = -4.46, P &lt; 0.001) were associated with low psychosocial HRQOL (F [9, 271] = 17.18, P &lt; 0.001).ConclusionsFindings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children

Diabetes Mellitus in Children with Acute Recurrent and Chronic Pancreatitis: Data From the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE Cohort.

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 of 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, body mass index 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:24 children (6.0% 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% CI 3.0, 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)). CONCLUSIONS: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

INternational Study Group of Pediatric Pancreatitis

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