BACKGROUND:Mutations in genes encoding cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (SPINK1) and chymotrypsinogen C (CTRC) are associated with chronic pancreatitis. However, in many patients with a familial chronic pancreatitis pattern suggesting a genetic cause, no mutations in either of these genes can be found, indicating that other, still unknown, associated genes exist. In this respect ATP8B1 is an interesting candidate due to its strong expression in the pancreas, its supposed general function in membrane organization and the higher incidence of pancreatitis in patients with ATP8B1 deficiency. METHODS:We analyzed all 27 ATP8B1 coding exons and adjacent non-coding sequences of 507 chronic pancreatitis patients by direct sequencing. Exons that harbored possible relevant variations were subsequently sequenced in 1,027 healthy controls. RESULTS:In the exonic regions, 5 novel non-synonymous alterations were detected as well as 14 previously described alterations of which some were associated with ATP8B1 deficiency. However, allele frequencies for any of these variations did not significantly differ between patients and controls. Furthermore, several non-synonymous variants were exclusively detected in control subjects and multiple variants in the non-coding sequence were identified with similar frequencies in both groups. CONCLUSIONS:We did not find an association between heterozygous ATP8B1 variants and chronic pancreatitis in our cohort of patients with hereditary and idiopathic chronic pancreatitis.

OBJECTIVES:To evaluate the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) in the detection of chronic pancreatitis (CP)-specific changes in the pediatric population. METHODS:The study included 48 children with pancreatic disorders subjected to both endoscopic retrograde cholangiopancreatography (ERCP) and MRCP within a 1- to 4-month interval. The sensitivity, specificity, positive predictive value, and negative predictive value of MRCP in the detection of CP-specific changes were determined using ERCP as a diagnostic standard. RESULTS:Diagnostic ERCP pancreatograms were obtained in 41 (85.4%) of 48 patients and diagnostic MRCP images in all 48 children. The sensitivity and positive predictive value of MRCP were 77.1% and 90%, respectively, and its specificity and negative predictive value amounted to 50% and 27.3%, respectively. The patients with consistent results of MRCP and ERCP (ie, true-positive and true-negative cases) and individuals with incompatible results of the tests (ie, false-positive and false-negative cases) differed in terms of their median age at MRCP (14.17 vs 10.33 years) and median CP stage according to the Cambridge Scale (4 vs 2). CONCLUSIONS:Magnetic resonance cholangiopancreatography provides diagnostic information equivalent to ERCP in a large percentage of pediatric patients with CP and should be used as the imaging method of choice, especially if the likelihood of therapeutic intervention is low.

OBJECTIVE:The aim of this study was to report on the short-and long-term outcomes of surgery for chronic pancreatitis (CP) in children. METHODS:All the children, who underwent surgery for CP between August 2007 and July 2019 in the Department of Surgical gastroenterology, Institute of Postgraduate Medical Education and Research, Kolkata, India were retrospectively reviewed. RESULTS:Of the total 54 patients, 33 (61%) were girls. The median age at operation was 16.5 years. The median duration between onset of pain and surgery was 36 months. 26% of patients were referred after failure of endotherapy. The most common indication for surgery was pain (94%). Surgery performed included modified Puestow (n = 26), Frey (n = 25), and Izbicki procedures. Twelve postoperative complications developed in ten (18.5%) patients. Most common complication was wound infection. Pancreatic leak developed in four (7.4%) patients (type A = 3, type B = 1). Median postoperative hospital stay was 8 days. There was no in-hospital mortality. Over a median follow-up of 48 months, 83% of patients had complete pain control. Weight gain was achieved in 77% of patients. New-onset diabetes and exocrine insufficiency developed in 4 and 14% of patients, respectively. CONCLUSIONS:Surgery is safe with fairly acceptable perioperative complications and good long-term pain control.

Severe hypertriglyceridemia is a well-known cause of pancreatitis. Usually, there is a moderate increase in plasma triglyceride level during pregnancy. Additionally, certain pre-existing genetic traits may render a pregnant woman susceptible to development of severe hypertriglyceridemia and pancreatitis, especially in the third trimester. To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL), apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis. DNA sequencing showed that three out of five patients had the same homozygous variation, p.G185C, in APOA5 gene. One patient had a compound heterozygous mutation, p.A98T and p.L279V, in LPL gene. Another patient had a compound heterozygous mutation, p.A98T & p.C14F in LPL and GPIHBP1 gene, respectively. No mutations were seen in APOC2 or LMF1 genes. All patients were diagnosed with partial LPL deficiency in non-pregnant state. As revealed in our study, genetic variants appear to play an important role in the development of severe gestational hypertriglyceridemia, and, p.G185C mutation in APOA5 gene appears to be the most common variant implicated in the Chinese population. Antenatal screening for mutations in susceptible women, combined with subsequent interventions may be invaluable in the prevention of potentially life threatening gestational hypertriglyceridemia-induced pancreatitis.

OBJECTIVES:We compared outcomes of acute alcoholic pancreatitis (AAP), acute biliary pancreatitis (ABP), and post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). METHODS:This was a retrospective cohort study conducted at a tertiary care center between June 2007 and June 2012. RESULTS:A total of 300 (68%) patients were diagnosed with AAP, 88 (20%) with ABP, and 55 (12%) with PEP. Longer length of hospital stay (LOHS) was more common in ABP (23%) as compared with AAP (10%) and PEP (7%, P = 0.025). Pseudocyst (P = 0.048), organ failure (OF) (P = 0.01), need for interventions (P ≤ 0.001), and mortality (P = 0.002) occurred more in ABP as compared with other groups. Systemic inflammatory response syndrome was associated with LOHS of more than 10 days (P = 0.01) and multi-OF (P = 0.05). Chronic pancreatitis was associated more with pseudocyst (P < 0.001) and mortality (P = 0.03). Serum urea nitrogen of greater than 25 g/dL predicted LOHS of more than 10 days (P = 0.02), OF (P < 0.001), multi-OF (P < 0.001), and persistent OF (P < 0.001). CONCLUSIONS:Acute biliary pancreatitis is a more severe disease compared with PEP and AAP. Chronic pancreatitis, systemic inflammatory response syndrome, and high serum urea nitrogen are important predictors of morbidity.

OBJECTIVE:Describe the surgical technique, complications, and long-term outcomes of total pancreatectomy and islet autotransplantation (TP-IAT) in a large series of pediatric patients. BACKGROUND:Surgical management of childhood pancreatitis is not clear; partial resection or drainage procedures often provide transient pain relief, but long-term recurrence is common due to the diffuse involvement of the pancreas. Total pancreatectomy (TP) removes the source of the pain, whereas islet autotransplantation (IAT) potentially can prevent or minimize TP-related diabetes. METHODS:Retrospective review of 75 children undergoing TP-IAT for chronic pancreatitis who had failed medical, endoscopic, or surgical treatment between 1989 and 2012. RESULTS:Pancreatitis pain and the severity of pain statistically improved in 90% of patients after TP-IAT (P < 0.001). The relief from narcotics was sustained. Of the 75 patients undergoing TP-IAT, 31 (41.3%) achieved insulin independence. Younger age (P = 0.032), lack of prior Puestow procedure (P = 0.018), lower body surface area (P = 0.048), higher islet equivalents (IEQ) per kilogram body weight (P = 0.001), and total IEQ (100,000) (P = 0.004) were associated with insulin independence. By multivariate analysis, 3 factors were associated with insulin independence after TP-IAT: (1) male sex, (2) lower body surface area, and (3) higher total IEQ per kilogram body weight. Total IEQ (100,000) was the single factor most strongly associated with insulin independence (odds ratio = 2.62; P < 0.001). CONCLUSIONS:Total pancreatectomy and islet autotransplantation provides sustained pain relief and improved quality of life. The β-cell function is dependent on islet yield. Total pancreatectomy and islet autotransplantation is an effective therapy for children with painful pancreatitis that failed medical and/or endoscopic management.

OBJECTIVE:The 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). METHODS:From 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. RESULTS:One 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. CONCLUSIONS:Therapeutic 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.

BACKGROUND:Studies have increasingly challenged the traditional management of acute pancreatitis (AP) with bowel rest. However, these studies used a low-fat diet or transgastric feeding and only included adults. Aiming to generate higher-quality prospective pediatric data, we compared the traditional approach of fasting and intravenous fluids and early enteral feeding with standard diet or formula. METHODS:Randomized controlled trial of children (2-18 years) with mild-moderate AP. Patients were randomly assigned 1:1 to initial fasting and intravenous fluids or an immediate, unrestricted diet. Pain scores, blood measures, and cross-sectional imaging were recorded throughout admission and follow-up. The primary outcome was time to discharge, and secondary outcomes were clinical and biochemical resolution and local and systemic complication rates. RESULTS:Of 33 patients (17 [52%] boys, mean age of 11.5 [±4.8] years), 18 (55%) were randomly assigned to early feeding and 15 (45%) were randomly assigned to initial fasting. We recorded the median (interquartile range [IQR]) time to discharge (2.6 [IQR 2.0 to 4.0] vs 2.9 [IQR 1.8 to 5.6]; = .95), reduction in serum lipase levels by day 2 (58% [IQR 2% to 85%] vs 48% [IQR 3% to 71%]; = .65), and readmission rates (1 of 18 [6%] vs 2 of 15 [13%]; = .22) between the early feeding and fasting cohorts, respectively. Immediate or delayed complication rates did not differ. Patients randomly assigned to early feeding had weight gain of 1.3 kg (IQR 0.29 to 3.6) at follow-up, compared with weight loss of 0.8 kg (IQR -2.1 to 0.7) in fasted patients ( = .028). CONCLUSIONS:This is the first randomized controlled trial in pediatric AP. There was no difference between early commencement of a standard oral diet and initial fast in any of the major outcome measures.

Chronic pancreatitis is an emerging and poorly understood disease in childhood. Total pancreatectomy with islet cell autotransplantation is being proposed as a treatment for chronic pancreatitis and recent studies report a more favorable outcome in children compared to adults. Herein, we review the therapeutic alternatives for pediatric chronic pancreatitis, focusing primarily on TP/IAT.

BACKGROUND:Chronic pancreatitis (CP) is a rare disease in childhood. Although ERCP is commonly performed in children, the effect of pancreatic duct stenting therapy in children with CP is unknown. OBJECTIVE:To investigate the efficacy of pancreatic duct stenting in children with CP. DESIGN:Retrospective analysis. SETTING:National referral center. PATIENTS:A total of 208 children with CP hospitalized between 1988 and 2012. INTERVENTIONS:ERCP with pancreatic duct stenting. MAIN OUTCOME MEASUREMENTS:Results of endoscopic therapy and number of pancreatitis episodes per year before and after treatment. RESULTS:A total of 223 pancreatic duct stenting procedures were performed in 72 children. The median number of stent replacements was 3 (range 1-21). A statistically significant decrease in the number of pancreatitis episodes per year was observed: from 1.75 to 0.23 after endoscopic treatment (P < .05). Pancreatic duct stenting was performed more frequently in patients with hereditary pancreatitis (61.5%) and in children with CP and anatomic anomalies of the pancreatic duct (65%; P < .05). LIMITATIONS:Retrospective analysis with the assessment of adverse events based on medical history. CONCLUSION:Pancreatic duct stenting therapy is a safe and effective procedure in children with CP. This therapy should be recommended especially for children with hereditary pancreatitis and patients with anatomic anomalies of the pancreatic duct.

OBJECTIVES:Several genetic risk factors have been identified in adults with idiopathic acute recurrent pancreatitis (IARP). However, the literature regarding the genetics of IARP is sparse in children. In this study, we aimed to analyze the genetic risk factors in children with IARP. METHODS:All children (< 18 years) with ARP from January 2015 to May 2018 were prospectively enrolled in the study. Children with a known cause of ARP like obstructive, toxic/metabolic, and autoimmune were excluded from the final analysis. Children with IARP underwent genetic testing for mutations/polymorphisms in genes known to predispose to pancreatitis including cationic trypsinogen protease serine 1 (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator gene (CFTR), chymotrypsin C (CTRC), claudin-2 (CLDN2) and cathepsin B (CTSB). RESULTS:A total of 239 children (116 boys, 10.3 ± 3.7 years) were enrolled during the study period. Of these, 204 (85.35%) children were identified as IARP. The mean age of symptom onset and the number of pancreatitis episodes were 8.3 ± 3.7 years and 3.3 ± 1.8, respectively. A family history of pancreatitis was noted in 4.6% children. Mutations/polymorphisms in at least 1 gene were identified in 89.5% (129/144) children including SPINK1 in 41.9%, PRSS1 (rs10273639) in 58.2%, CTRC in 25.6%, CTSB in 54.9%, CLDN2 in 72.9%, and CFTR in 2.3%. There was no significant incidence of genetic mutations/polymorphisms in IARP with or without pancreas divisum (95.7 vs 88.4%; p = 0.467). CONCLUSIONS:Genetic alterations are present in the majority of the children with IARP. The incidence of genetic mutations is similar in children with or without pancreas divisum.

OBJECTIVES:Little is known about risk factors for biliary pancreatitis in children. We characterized cases of pediatric biliary pancreatitis, compared biliary with nonbiliary cases, examined differences in presentation between younger and older children, and studied features distinguishing gallstone- from sludge-induced pancreatitis. METHODS:We evaluated 76 episodes of biliary pancreatitis from 271 cases of acute pancreatitis in children admitted to a tertiary care hospital from 1994 to 2007. RESULTS:Of the 76 cases, 55% had gallstones, 21% had sludge, and 24% had structural defects. Hispanic children had 2.85 (P = 0.01) and 5.59 (P = 0.003) times higher probability for biliary pancreatitis than white and black children, respectively. Median serum amylase and lipase in children with biliary pancreatitis were 64% and 49% higher, respectively, compared with other causes (P < 0.05). In multiple logistic regression, aspartate aminotransferase was an independent predictor of biliary pancreatitis (odds ratio 6.69, P = 0.001). When comparing gallstone- with sludge-induced causes, obesity was an independent predictor (38% more prevalent, P < 0.01) of gallstone cases. CONCLUSIONS:Hispanic ethnicity is a risk factor and aspartate aminotransferase is a biomarker for biliary pancreatitis over other causes. Furthermore, obesity can distinguish gallstone- from sludge-induced pancreatitis. These findings may spur prospective studies to determine the optimal evaluation and management of children with biliary pancreatitis.

Acute, acute recurrent, and chronic forms of pancreatitis have been increasingly diagnosed in children in the past 2 decades. Risk factors in the pediatric group are broad and appear to be strikingly different compared with the adult cohort. However, the disease burden and impact on quality of life are surprisingly similar in children and adults. This review summarizes the definitions, epidemiology, risk factors, diagnosis, and management of pediatric pancreatitis, identifies features that are unique to the childhood-onset disease, identifies gaps, and proposes recommendations for future opportunities.

Pancreatic disease in children has a wide clinical spectrum and may present as Acute pancreatitis (AP), Acute recurrent pancreatitis (ARP), Chronic pancreatitis (CP) and Pancreatic disease without pancreatitis. This article highlights the etiopathogenesis and management of pancreatitis in children along with clinical data from five tertiary care hospitals in south India [Chennai (3), Cochin and Pune].

Acute recurrent pancreatitis (ARP) is defined as two distinct episodes of acute pancreatitis (AP), whereas chronic pancreatitis (CP) is caused by persistent inflammation of the pancreas. In children they are caused by genetic mutations, autoimmune pancreatitis, congenital pancreatic abnormalities, and other conditions. Acute recurrent pancreatitis is frequently a precursor to CP, and both are thought to be on the same disease continuum. In particular, genetic factors are associated with early progression of ARP to CP. The diagnosis of CP, as in AP, is based on clinical findings, biochemical tests, and imaging studies. Findings of exocrine pancreatic dysfunction are also important in the diagnosis of CP. A step-up strategy has become increasingly standard for the treatment of patients with CP. This strategy starts with endoscopic treatment, such as pancreatic sphincterotomy and stenting, and progresses to surgery should endoscopic therapy fail or prove technically impossible. Non-opioid (e.g. ibuprofen / naproxen) and opioid (e.g. oxycodone) forms of analgesia are widely used in pediatric patients with AP or CP, whereas pancreatic enzyme replacement therapy may be beneficial for patients with abdominal pain, steatorrhea, and malnutrition. Despite the disparity in the age of onset, pediatric CP patients display some similarities to adults in terms of disease progress. To reduce the risk of developing pancreatic exocrine inefficiency, diabetes and pancreatic cancer in the future, clinicians need to be aware of the current diagnostic approach and treatment methods for ARP and CP and refer them to a pediatric gastroenterologist in a timely manner.