International Study Group Of Pediatric Pancreatitis: In Search For A Cure Research Articles

Causal Evaluation of Pancreatitis in Children

Pancreatitis in childhood is not common. It can be associated with severe morbidity and mortality. The role of clinicalevaluation is vital as it can be misdiagnosed easily. This study was aimed to review the prevalence, etiology,presentation and outcome of pancreatitis in children. This cross-sectional study was conducted at the Department ofPediatric Gastroenterology & Nutrition of Bangabandhu Sheikh Mujib Medical University, Dhaka from January,2017 through June, 2018. A total 43 cases of pancreatitis were included in this study. Pancreatitis was classified asacute pancreatitis(AP), acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) as per diagnostic criteriamade by INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) group. Among 43children (age 10.1 mean ± 2.55,18 males); AP,14 (32.6%); ARP, 14(32.6%) and CP,15(34.8 %). Half of AP wasidiopathic. Majority of ARP (28.6%) were idiopathic and CP (40%) had calcific pancreatitis. Majority of patients hadvomiting followed by moderate to severe abdominal pain. In CP 4(26.6%) patient developed diabetes mellitus.Majority of pancreatitis in children is idiopathic. A sub-set of AP goes on to develop ARP and CP on follow-up andbeing in the idiopathic sub-set is a risk factor. CP is progress to endocrine and exocrine insufficiency. Early diagnosis,close monitoring and proper intervention are mandatory to reduce the potential morbidity and mortality. Bangabandhu Sheikh Mujib Med. Coll. J. 2022;1(2):76-79

A Better Understanding of Pediatric Autoimmune Pancreatitis: Over 13 Years of Experience.

Pediatric autoimmune pancreatitis (P-AIP) is an uncommon disease whose diagnosis requires strong clinical suspicion. Late diagnosis increases morbidity. We aimed to compare the usefulness of the 2011 International Consensus Diagnostic Criteria (ICDC) for Autoimmune Pancreatitis with the 2018 INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) criteria. We retrospectively analyzed demographics and clinical, laboratory, radiological, and histological findings at diagnosis and during long-term follow-up in children diagnosed with AIP in 2 tertiary hospitals between 2008 and 2021. We included 11 patients [6 girls; median age at diagnosis, 12.5 (range 2.8-15.7) years]. The most common symptom was abdominal pain. Pancreatic enzymes were elevated in 10 patients, and serum immunoglobulin G4 was elevated in 1. Magnetic resonance imaging showed enlargement of the pancreatic head in 10 patients and general pancreatic enlargement in 1. Pancreatic and papilla tissue were obtained from 9 patients. All patients received corticosteroids (prednisolone), and 4 also received azathioprine. According to the ICDC, all patients were classified as probable or non-otherwise specified AIP. According to INSPPIRE criteria, all patients were classified as AIP. Using the INSPPIRE criteria would have avoided biopsies in 6 patients who responded well to corticosteroids. The INSPPIRE criteria are useful. Using the ICDC in pediatric patients can delay diagnosis and result in unnecessary invasive tests.

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. The purpose of this study is to evaluate the interobserver agreement among experienced pediatric radiologists for subjective, quantitative, and semiquantitative 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 (International Study Group of Pediatric Pancreatitis: In Search for a Cure) 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 categoric imaging findings of chronic pancreatitis and measured pancreas thickness and pancreatic duct diameter. Agreement was assessed using kappa coefficients for the categoric variables and intraclass correlation coefficients (ICCs) for the continuous variables. RESULTS. A total of 76 CT and 80 MRI examinations performed in 110 children (65 girls and 45 boys; mean age, 11.3 ± 4.6 [SD] years) were reviewed. For CT, kappa coefficients for categoric findings ranged from -0.01 to 0.81, with relatively high kappa coefficients noted for parenchymal calcifications (κ = 0.81), main pancreatic duct dilatation (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. The ICC for duct diameter was 0.85. For MRI, kappa coefficients for categoric findings ranged from -0.01 to 0.74, with relatively high kappa coefficients noted for main duct irregularity (κ = 0.74), side branch dilatation (κ = 0.70), number of dilated side branches (κ = 0.65), and main duct dilatation (κ = 0.64); kappa coefficient for atrophy was 0.52. ICCs for parenchymal thickness measurements ranged from 0.53 for the neck and body individually 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.

Imaging of Pancreatitis in Children

Pancreatitis in children has become more recognized over the past decade. Recent studies published by the INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE) Group categorizes pediatric pancreatitis according to various etiologies and clinical course of disease in acute pancreatitis (AP), acute recurrent pancreatitis (ARP) and chronic pancreatitis. Imaging modalities help fulfill the diagnosis of AP in cases of atypical clinical context, while imaging also completes the major diagnostic criteria in CP. Ultrasound is the modality of choice to evaluate children with AP. Computed tomography should be reserved to assess the severity of complicated AP, or in the acute traumatic setting due to radiation concerns in children. Magnetic resonance cholangiopancreatography is used for the evaluation of underlying pancreaticobiliary structural abnormalities and for diagnosing CP. The etiologies of pediatric pancreatitis are diverse and unique including biliary stones, pancreaticobiliary structural abnormalities, genetic mutationrelated, drugs, trauma, systemic diseases and autoimmune-related cause. This article provides a pictorial review of the imaging modalities and findings related to the clinical course and etiologies of pediatric pancreatitis (AP, ARP and CP).

Vascular Complications in Pediatric Pancreatitis: A Case Series.

We reviewed INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) database for splanchnic venous thrombosis or arterial pseudoaneurysms to determine the incidence, risk factors and outcomes of peripancreatic vascular complications in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Of 410 children with diagnostic imaging studies, vascular complications were reported in five (1.2%); two had ARP, three CP. The vascular events were reported during moderately severe or severe acute pancreatitis (AP) in four, mild AP in one. Venous thrombosis occurred in four, arterial pseudoaneurysm (left gastric artery) in one. Two patients with venous thrombosis were treated with anticoagulant, one achieved recanalization (splenic vein). In two patients who did not receive anticoagulants, one re-canalized. No adverse effects were observed with anticoagulants. The child with pseudoaneurysm underwent aneurysmal coiling. Anti-coagulants appear to be safe in children with acute pancreatitis, their long-term benefit needs to be further investigated.

Varied Presentations and Comorbidities in Pediatric Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) is a chronic inflammatory condition rarely reported in children. In 2018, to standardize the approach to AIP, INternational Study Group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) defined AIP, outlined the clinical course, and developed diagnostic and therapeutic recommendations. We performed a retrospective review of cases at our institution from January 1, 2016, to June 1, 2019, and compared their presentations with the INSPPIRE guidelines. Our patients showed variable laboratory, radiographic, and histologic findings, highlighting the difficulty in diagnosing AIP. Histologic samples were obtained in our patients due to diagnostic uncertainty, which ultimately confirmed the diagnosis. One patient was diagnosed with autoimmune hepatitis coexistent with AIP, which has not been previously described in the pediatric population. Exocrine and endocrine complications of AIP were also noted. In all cases, symptoms improved following treatment, and decompression of the common bile duct was seen on repeat imaging.

Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From the INSPPIRE Study.

The 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. Data 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. Out 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 < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (P < 0.0001). This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-United States sites need to be further explored.

Factors Associated With Frequent Opioid Use in Children With Acute Recurrent and Chronic Pancreatitis.

The 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). Cross-sectional study of children <19 years with ARP or CP, at enrollment into the INSPPIRE cohort. We categorized patients as opioid "frequent use" (daily/weekly) or "nonfrequent use" (monthly or less, or no opioids), based on patient and parent self-report. Of 427 children with ARP or CP, 17% reported frequent opioid use. More children with CP (65%) reported frequent opioid use than with ARP (41%, P = 0.0002). In multivariate analysis, frequent opioid use was associated with older age at diagnosis (odds ratio [OR] 1.67 per 5 years, 95% confidence interval [CI] 1.13-2.47, P = 0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, P = 0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, P < 0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, P < 0.0001). Children with frequent opioid use also reported more missed school days, hospitalizations, and emergency room visits in the past year than children with no frequent use (P < 0.0002 for each). Participants in the US West and Midwest accounted for 83% of frequent opioid users but only 56% of the total cohort. In children with CP or ARP, frequent opioid use is associated with constant pain, more healthcare use, and higher levels of pain interference with functioning. Longitudinal and prospective research is needed to identify risk factors for frequent opioid use and to evaluate nonopioid interventions for reducing pain and disability in these children.

Acute pancreatitis in children - a retrospective observational study in a South Indian tertiary care hospital

Background & Aims: Acute pancreatitis is usually rare in childhood but probably more commonly diagnosed nowadays. This condition should be considered in the evaluation of children with vomiting and abdominal pain. In this study, we analyse the clinical presentation and outcome of children presenting with acute pancreatitis in a tertiary care centre. Materials & Methods: All children less than 15 years of age, admitted to the paediatric ward of a tertiary care hospital in South India between January 2016 to December 2018 were included in the study. Acute pancreatitis was diagnosed based on the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) Group criteria. Results: The etiology of acute pancreatitis could be identified in 13 out of 30 patients.The most common etiology was gallstones/ gallbladder sludge (7/30). Overall the incidence of pancreatitis had significant female preponderance 23:7. The average duration of hospital stay was 15 days. Seven patients had mild acute pancreatitis, 18 had moderately severe pancreatitis and 5 had severe pancreatitis. One child with severe acute pancreatitis died. Two of them had pseudocyst formation requiring percutaneous drainage under ultrasound guidance. There was no requirement of surgery in the study group. Conclusion: Our study provides data about the etiology and clinical course of acute pancreatitis in children in southern part of India. Unlike the previous studies, where most of the patients had mild acute pancreatitis, we had more patients with moderately severe and severe acute pancreatitis requiring more interventions and ICU care.

Web-based cognitive-behavioral intervention for pain in pediatric acute recurrent and chronic pancreatitis: Protocol of a multicenter randomized controlled trial from the study of chronic pancreatitis, diabetes and pancreatic cancer (CPDPC)

IntroductionAbdominal pain is common and is associated with high disease burden and health care costs in pediatric acute recurrent and chronic pancreatitis (ARP/CP). Despite the strong central component of pain in ARP/CP and the efficacy of psychological therapies for other centralized pain syndromes, no studies have evaluated psychological pain interventions in children with ARP/CP. The current trial seeks to 1) evaluate the efficacy of a psychological pain intervention for pediatric ARP/CP, and 2) examine baseline patient-specific genetic, clinical, and psychosocial characteristics that may predict or moderate treatment response. MethodsThis single-blinded randomized placebo-controlled multicenter trial aims to enroll 260 youth (ages 10–18) with ARP/CP and their parents from twenty-one INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) centers. Participants will be randomly assigned to either a web-based cognitive behavioral pain management intervention (Web-based Management of Adolescent Pain Chronic Pancreatitis; WebMAP; N = 130) or to a web-based pain education program (WebED; N = 130). Assessments will be completed at baseline (T1), immediately after completion of the intervention (T2) and at 6 months post-intervention (T3). The primary study outcome is abdominal pain severity. Secondary outcomes include pain-related disability, pain interference, health-related quality of life, emotional distress, impact of pain, opioid use, and healthcare utilization. ConclusionsThis is the first clinical trial to evaluate the efficacy of a psychological pain intervention for children with CP for reduction of abdominal pain and improvement of health-related quality of life. Findings will inform delivery of web-based pain management and potentially identify patient-specific biological and psychosocial factors associated with favorable response to therapy.Clinical Trial Registration #: NCT03707431.

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.

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. 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). 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)]. 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.

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

The 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. 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 (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. Of 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%). Children 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.

Pancreas Divisum in Pediatric Acute Recurrent and Chronic Pancreatitis: Report From INSPPIRE.

The 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. We 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. PD 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<0.01) or a family history of pancreatitis (P<0.05), and more likely to have hypertriglyceridemia (11% vs. 3%; P=0.03). Children with PD underwent significantly more endoscopic procedures and pancreatic sphincterotomy. Patients with PD had fewer attacks of acute pancreatitis (P=0.03) and were less likely to develop exocrine pancreatic insufficiency (P=0.01). Therapeutic endoscopic retrograde cholangiopancreatography was considered most helpful if pancreatic duct was impacted with stones (83% helpful). PD is likely a risk factor for acute recurrent pancreatitis and chronic pancreatitis in children that appears to act independently of genetic risk factors. Patients with PD and stones obstructing the pancreatic duct benefit most from therapeutic endoscopic retrograde cholangiopancreatography.

Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis

The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). 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. 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. 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.

Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations

To assess whether the age of onset was associated with unique features or disease course in pediatric acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Demographic and clinical information on children with ARP or CP was collected at INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE) centers. The Cochran-Armitage trend test and Jonckheere-Terpstra test were used to examine for differences between pediatric age groups (<6, 6-11, and ≥12 years). Between September 2012 and March 2016, 342 children with ARP or CP were enrolled; 129 (38%) were <6 years of age at the time of first diagnosis of acute pancreatitis, 111 (32%) were 6-11 years of age, and 102 (30%) were ≥12 years of age. Early-onset disease was associated with mutations in cationic trypsinogen (PRSS1) (P < .01), chymotrypsin C (CTRC) (P = .01), family history of acute pancreatitis (P = .02), family history of CP (P < .01), biliary cysts (P = .04), or chronic renal failure (P = .02). Later-onset disease was more commonly present with hypertriglyceridemia (P = .04), ulcerative colitis (P = .02), autoimmune diseases (P < .0001), or medication use (P < .01). Children with later-onset disease also were more likely to visit the emergency department (P < .05) or have diabetes (P < .01). Early-onset pancreatitis is associated strongly with PRSS1 or CTRC mutations and family history of pancreatitis. Children with later-onset disease are more likely to have nongenetic risk factors. Future studies are needed to investigate whether the disease course, response to therapy, or clinical outcomes differ relative to the timing of disease onset.

Acute Pancreatitis: What Is It, Why Is It on the Rise, and What Are the Current Nutrition Recommendations?

Acute pancreatitis (AP) is defined as reversible inflammation of the pancreatic parenchyma, subsequently setting off the systemic inflammatory response syndrome (SIRS). 1 Mekitarian Filho E. Carvalho WBd Silva F.D. Acute pancreatitis in pediatrics: A systematic review of the literature. J Pediatr. 2012; 88: 101-114 Crossref Scopus (17) Google Scholar , 2 Srinath A. Lowe M. Pediatric pancreatitis. Pediatr Rev Am Acad Pediatr. 2013; 34: 79-90 Crossref PubMed Scopus (39) Google Scholar , 3 Eckerwall G.E. Tingstedt B.B. Bergenzaun P.E. Andersson R.G. Immediate oral feeding in patients with mild acute pancreatitis is safe and may accelerate recovery: A randomized clinical study. Clin Nutr. 2007; 26: 758-763 Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar , 4 Morinville V.D. Husain S.Z. Harrison Bai B.B. et al. Definitions of pediatric pancreatitis and survey of current clinical practices: Report from INSPPIRE (International Study Group Of Pediatric Pancreatitis: In Search For A Cure). J Pediatr Gastroenterol Nutr. 2012; 55: 261 Crossref PubMed Scopus (294) Google Scholar , 5 Banks P.A. Bollen T.L. Dervenis C. et al. Classification of acute pancreatitis—2012: Revision of the Atlanta classification and definitions by international consensus. Gut. 2013; 62: 102-111 Crossref PubMed Scopus (3525) Google Scholar SIRS is an inflammatory state affecting the whole body, defined by the presence of two or more of the following criteria: heart rate >90 beats/min, core temperature <36°C or >38°C, white blood count <4,000/μL or >12,000/μL, and respirations greater than 20 breaths/min or partial pressure of carbon dioxide <32 mm Hg. 5 Banks P.A. Bollen T.L. Dervenis C. et al. Classification of acute pancreatitis—2012: Revision of the Atlanta classification and definitions by international consensus. Gut. 2013; 62: 102-111 Crossref PubMed Scopus (3525) Google Scholar The top leading causes of AP in children are biliary disease, drug-induced, idiopathic, systemic disease, and trauma, followed by metabolic, hereditary, and infectious diseases. 1 Mekitarian Filho E. Carvalho WBd Silva F.D. Acute pancreatitis in pediatrics: A systematic review of the literature. J Pediatr. 2012; 88: 101-114 Crossref Scopus (17) Google Scholar , 6 Restrepo R. Hagerott H.E. Kulkarni S. Yasrebi M. Lee E.Y. Acute pancreatitis in pediatric patients: Demographics, etiology, and diagnostic imaging. Am J Roentgenol. 2016; 206: 632-644 Crossref PubMed Scopus (49) Google Scholar Common biliary diseases that lead to AP include biliary gallstones, biliary sludge, or anatomical anomalies of the ductal system such as sphincter of Oddi dysfunction, pancreas divisum, or annular pancreas. 1 Mekitarian Filho E. Carvalho WBd Silva F.D. Acute pancreatitis in pediatrics: A systematic review of the literature. J Pediatr. 2012; 88: 101-114 Crossref Scopus (17) Google Scholar In pediatrics, the most commonly reported cases of drug-induced AP are caused by valproic acid and l-asparaginase. 1 Mekitarian Filho E. Carvalho WBd Silva F.D. Acute pancreatitis in pediatrics: A systematic review of the literature. J Pediatr. 2012; 88: 101-114 Crossref Scopus (17) Google Scholar Systemic diseases leading to AP include sepsis, shock, hemolytic uremic syndrome, systemic lupus erythematosus, inflammatory bowel disease, and diabetes mellitus. 2 Srinath A. Lowe M. Pediatric pancreatitis. Pediatr Rev Am Acad Pediatr. 2013; 34: 79-90 Crossref PubMed Scopus (39) Google Scholar Traumatic abdominal injuries both nonaccidental and accidental, such as those sustained from motor vehicle accidents, sports injuries, and falls, can result in AP. 1 Mekitarian Filho E. Carvalho WBd Silva F.D. Acute pancreatitis in pediatrics: A systematic review of the literature. J Pediatr. 2012; 88: 101-114 Crossref Scopus (17) Google Scholar , 6 Restrepo R. Hagerott H.E. Kulkarni S. Yasrebi M. Lee E.Y. Acute pancreatitis in pediatric patients: Demographics, etiology, and diagnostic imaging. Am J Roentgenol. 2016; 206: 632-644 Crossref PubMed Scopus (49) Google Scholar Genetic mutations are a less common cause of AP. 1 Mekitarian Filho E. Carvalho WBd Silva F.D. Acute pancreatitis in pediatrics: A systematic review of the literature. J Pediatr. 2012; 88: 101-114 Crossref Scopus (17) Google Scholar , 2 Srinath A. Lowe M. Pediatric pancreatitis. Pediatr Rev Am Acad Pediatr. 2013; 34: 79-90 Crossref PubMed Scopus (39) Google Scholar Effective Treatment for Acute Pancreatitis Depends on Underlying EtiologiesJournal of the Academy of Nutrition and DieteticsVol. 119Issue 4PreviewHeinzman and colleagues,1 in the Practice Applications section of the June 2018 issue of this Journal, discuss the increasing incidence of acute pancreatitis (AP) in the pediatric population, emphasizing the lack of data on medical nutrition therapy for this condition. They discuss the lack of clarity among dietitians about the term “low-fat diet” for treatment for this population. A sample of dietitians surveyed recommended definitions varying from <10% to <30% of calories from fat. Some dietitians did not recommend a low-fat diet for patients with AP. Full-Text PDF

Risk Factors Associated With Pediatric Acute Recurrent and Chronic Pancreatitis: Lessons From INSPPIRE.

Pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood. To characterize and identify risk factors associated with ARP and CP in childhood. A 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. Demographic characteristics, risk factors, abdominal pain, and disease burden. A 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 < .001). Children with PRSS1 or SPINK1 mutations were more likely to present with CP compared with ARP (PRSS1: OR = 4.20; 95% CI, 2.14-8.22; P < .001; and SPINK1: OR = 2.30; 95% CI, 1.03-5.13; P = .04). Obstructive risk factors did not differ between children with ARP or CP (33% in both the ARP and CP groups), but toxic/metabolic risk factors were more common in children with ARP (21% overall; 26% in the ARP group and 15% in the CP group; OR = 0.55; 95% CI, 0.31-0.99; P = .046). Pancreatitis-related abdominal pain was a major symptom in 81% of children with ARP or CP within the last year. The disease burden was greater in the CP group compared with the ARP group (more emergency department visits, hospitalizations, and medical, endoscopic, and surgical interventions). Genetic mutations are common in both ARP and CP. Ethnicity and mutations in PRSS1 or SPINK1 may influence the development of CP. The high disease burden in pediatric CP underscores the importance of identifying predisposing factors for progression of ARP to CP in children.

Direct Costs of Acute Recurrent and Chronic Pancreatitis in Children in the INSPPIRE Registry.

To estimate selected direct medical care costs of children with chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). 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. 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. 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.

Design and implementation of INSPPIRE.

Acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are rare and poorly understood diseases in children. Better understanding of these disorders can only be accomplished via a multicenter, structured, data collection approach. The International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) consortium was created to investigate the epidemiology, etiologies, pathogenesis, natural history, and outcomes of pediatric ARP and CP. Patient and physician questionnaires were developed to capture information on demographics, medical history, family and social history, medications, hospitalizations, risk factors, diagnostic evaluation, treatments, and outcome information. Information collected in paper questionnaires was then transferred into Research Electronic Data Capture (REDCap), tabulated, and analyzed. The administrative structure of the INSPPIRE consortium was established, and National Institutes of Health funding was obtained. A total of 14 sites (10 in the United States, 2 in Canada, and 2 overseas) participated. Questionnaires were amended and updated as necessary, followed by changes made into the REDCap database. Between September 1, 2012 and August 31, 2013, a total of 194 children were enrolled into the study: 54% were girls, 82% were non-Hispanic, and 72% were whites. The INSPPIRE consortium demonstrates the feasibility of building a multicenter patient registry to study the rare pediatric diseases, ARP and CP. Analyses of collected data will provide a greater understanding of pediatric pancreatitis and create opportunities for therapeutic interventional studies that would not otherwise be possible without a multicenter approach.

Definitions of Pediatric Pancreatitis and Survey of Present Clinical Practices

There is limited literature on acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP) in children. The International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) consortium was formed to standardize definitions, develop diagnostic algorithms, investigate disease pathophysiology, and design prospective multicenter studies in pediatric pancreatitis. Subcommittees were formed to delineate definitions of pancreatitis, and a survey was conducted to analyze present practice. AP was defined as requiring 2 of the following: abdominal pain compatible with AP, serum amylase and/or lipase values ≥3 times upper limits of normal, and imaging findings of AP. ARP was defined as ≥2 distinct episodes of AP with intervening return to baseline. CP was diagnosed in the presence of typical abdominal pain plus characteristic imaging findings, or exocrine insufficiency plus imaging findings, or endocrine insufficiency plus imaging findings. We found that children with pancreatitis were primarily managed by pediatric gastroenterologists. Unless the etiology was known, initial investigations included serum liver enzymes, triglycerides, calcium, and abdominal ultrasound. Further investigations (usually for ARP and CP) included magnetic resonance or other imaging, sweat chloride, and genetic testing. Respondents' future goals for INSPPIRE included determining natural history of pancreatitis, developing algorithms to evaluate and manage pancreatitis, and validating diagnostic criteria. INSPPIRE represents the first initiative to create a multicenter approach to systematically characterize pancreatitis in children. Future aims include creation of patient database and biologic sample repository.