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Masses and masslike lesions of the pancreas are uncommon in the pediatric population. However, owing to overlapping clinical and imaging features, it can be challenging to differentiate the various causes of pediatric pancreatic masses at initial patient presentation. Clinical data such as patient age, signs and symptoms at presentation, laboratory test results, and potential underlying cancer predisposition syndrome can be helpful when formulating a differential diagnosis. US may be the first imaging study to depict a pancreatic mass in a child, as this examination is frequently performed in children with nonspecific abdominal signs and symptoms because of its wide availability and relatively low cost and the lack of a need for sedation or anesthesia. CT or MRI is typically required for more thorough characterization of the mass and surgical planning. Complete characterization of pancreatic masses includes assessment of vascular involvement, local invasion, and extrapancreatic spread of tumor. The authors provide an up-to-date comprehensive review of the clinical manifestations, histopathologic features, and imaging findings of primary and secondary tumors of the pancreas in children and young adults. Advances in imaging, current prognostic information, and treatment paradigms also are highlighted. Finally, nontumorous masslike lesions of the pediatric pancreas, including vascular malformations, cystic disorders (eg, von Hippel-Lindau syndrome, cystic fibrosis), intrapancreatic accessory spleen, and autoimmune pancreatitis, are discussed.

Objective: To assess the degree, duration, mean absolute relative difference (MARD), and error analysis of discrepant values per continuous glucose monitoring (CGM) systems after hydroxyurea (HU) administration. Research Design and Methods: Inpatient glucometer and CGM data from 16 total pancreatectomy/islet autotransplantation patients using Dexcom Professional G4 and 12 patients using Dexcom G6 were analyzed after daily dosing with HU. Timing of HU dosing and median of 9.5 days of sensor and glucometer values were assessed per patient. Results: A large positive elevation of sensor readings was identified after HU dosing. The greatest discrepancy between glucometer and sensor readings occurred 0.5–2 h after HU administration [G4 (mean 3.0 mmol/L, median 2.4 mmol/L, MARD 55%), G6 (mean 4.2 mmol/L, median 4.6 mmol/L, MARD 91%)]. The discrepancy was

BACKGROUND AND AIMS: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield. METHODS: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders. RESULTS: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1–4)]. ERCP was more common in those with obstructed pancreatic duct (p=0.0009), pancreas divisum (p=0.0009), prior pancreatic surgery (p=0.005), and longer disease duration (p=0.004). A greater number of ERCPs was associated with disease duration (p

Total pancreatectomy with islet autotransplantation is a complex surgical approach for acute recurrent or chronic pancreatitis that frequently triggers extreme thrombocytosis (platelets ≥ 1000 × 109 /L). Thrombocytosis can be prothrombotic, so cytoreductive hydroxyurea is often initiated after this surgery; however, optimal dosing strategy and efficacy are unknown. This prospective pilot study characterized the pharmacokinetics of hydroxyurea after this procedure in children. It also compared them with previously published pediatric parameters in sickle cell anemia (SCA), the disease in which pediatric hydroxyurea pharmacokinetics have primarily been studied. Plasma hydroxyurea levels were quantified in 14 participants aged 4-19 years using high-performance liquid chromatography. Blood collections were scheduled 20 minutes, 1 hour, and 4 hours after the first dose, on pharmacokinetic day 1 (PK1), and again 2-3 months later if still on hydroxyurea (PK2). Six participants had PK1 and PK2 data at all 3 postdose timed collections, 5 only had PK1 samples, and 3 only had PK2 samples. Total pancreatectomy with islet autotransplantation participants had reduced and delayed absorption compared with sickle cell anemia participant data from the Hydroxyurea Study of Long-Term Effects, regardless of timing or dosing methodology. Total pancreatectomy with islet autotransplantation participants had different pharmacokinetic profiles at PK1 versus PK2, with lower dose-normalized exposures than previously reported in sickle cell anemia. These results suggest variability exists in hydroxyurea absorption and bioavailability in total pancreatectomy with islet autotransplantation patients, suspected to be primarily because of Roux-en-Y reconstruction, and suggest that more pharmacokinetic data are needed for scenarios when hydroxyurea is prescribed to children without sickle cell anemia.

The etiology of portal hypertension (pHTN) in children differs from that of adults and may require different management strategies. We set out to review the etiology, management, and natural history of pHTN at a pediatric liver center. From 2008 to 2018, 151 children and adolescents with pHTN were identified at a free‐standing children’s hospital. Patients were stratified by etiology of pHTN (intrahepatic disease [IH], defined as cholestatic disease and fibrotic or hepatocellular disease; extrahepatic disease [EH], defined as hepatic vein obstruction and prehepatic pHTN). Patients with EH were more likely to undergo an esophagoduodenscopy for a suspected gastrointestinal bleed (77% vs. 41%; P

Hematologic trends after pancreatectomy with islet autotransplantation (IAT), which involves splenectomy, have been rarely studied. Reactive thrombocytosis (RT, platelets ≥500 K/μL) often occurs postoperatively, similar to other postsplenectomy states, but the degree of similarities and true incidence are unknown.A single-site, retrospective, observational cohort study of patients who underwent total splenectomy between 2010 and 2018 was performed. Thrombocytosis incidence and pharmacologic management strategies were evaluated, including cohort-based analyses for IAT versus other splenectomy indications.Analyses included 112 patients overall, 42 of whom underwent IAT. RT occurred frequently (93.8%) despite most patients having normal preoperative platelet counts. IAT patients had significantly higher peak platelet counts compared to non-IAT patients and the rate of platelet rise for IAT patients was significantly faster. IAT was uniquely predictive of developing extreme thrombocytosis (ExT, platelets ≥1000 K/μL, 90% vs. 15.7%, risk ratio 4.11, P 0.0001) despite standardized hydroxyurea use. Thrombotic events were infrequent and did not differ between groups.RT was common regardless of splenectomy indication but ExT was uniquely associated with IAT despite cytoreductive pharmacotherapy. These results strongly suggest that splenectomy is unlikely to be the sole contributor to post-IAT RT but further investigations into this phenomenon are needed.Treatment study, Level III (retrospective comparative study).

Pancreatectomy with islet autotransplantation (IAT) is a treatment option for children with debilitating chronic pancreatitis. Sterility cultures from preservation solutions are often positive, yet their impact has not been well studied in children. A retrospective review of all patients who underwent IAT from 2015 to 2018 at a single institution was performed. Sterility culture data were obtained from both the pancreas transport and islet transplant media. All patients received prophylactic perioperative meropenem and vancomycin for 72 h per our protocol. If cultures resulted positive, antibiotics were extended for a total of 7 days. Primary outcomes were postoperative fever and 30-day infectious complications. Forty-one patients underwent IAT during the study period. Seventeen (41.5 %) patients had negative cultures of both the transport and transplant media, while 24 (58.5 %) patients had a positive culture from either sample. Of these patients, 13 (31.7 %) were positive in both, 10 (24.4 %) were positive in only the transport media, and 1 (2.4 %) was positive in only the transplant media. Patients with positive transplant media were similar with regard to age, gender, etiology, and disease duration compared to those with negative transplant media (all p > 0.05), but the positive group was more likely to have a pancreatic stent in place at the time of surgery (38.5 % vs. 4.2 %, p = 0.01). The overall postoperative infectious complication rate was 31.2 % (n = 13). No difference was detected between the transplant positive and negative culture groups in postoperative fever or 30-day infectious complications (p > 0.05 for each). An existing pancreatic stent at the time of pancreatectomy with IAT is a risk factor for positive sterility cultures. However, positive islet transplant media culture was not associated with increased risk of post-IAT infection or morbidity in the setting of an empiric antibiotic protocol. Future work is necessary to study the optimal perioperative antibiotic regimen in pediatric IAT.

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.

Background Portal diversion by surgical shunt plays a major role in the treatment of medically refractory portal hypertension. We evaluate our center’s experience with surgical shunts for the treatment of pediatric portal hypertension. Methods All patients who underwent surgical shunt at a single institution from 2008 to 2017 were reviewed. The primary outcome was intervention-free shunt patency. Results In this study, 34 pediatric patients underwent portal shunt creation. The median age was 7.7 years (interquartile range 4.3–12.0). Twenty-nine patients (85%) had prehepatic portal hypertension and 5 patients (15%) had intrahepatic portal hypertension. The primary manifestations of portal hypertension were esophageal varices (97%) and gastrointestinal bleeding (77%). Eighteen patients (53%) underwent meso-Rex bypass, 10 patients (29%) underwent splenorenal shunt, and 6 patients (18%) underwent mesocaval shunt. Outcomes were notable for minimal wound complications (9%), rebleeding events (12%), and mortality (3%). In the postoperative setting, 10 patients (29%) experienced a shunt complication (occlusion or stenosis), 4 of which occurred in the early postoperative period and required urgent intervention. The 1-year and 5-year “primary patency” patency rates were 71% and 66%, respectively. Conclusion Children suffer significant morbidity from the sequelae of portal hypertension. Our experience reinforces the feasibility of surgical shunts as an effective treatment option associated with low rates of morbidity and mortality.

BACKGROUND Evidence for aspirin efficacy testing in pediatrics is limited, especially outside of cardiology, yet thrombotic events have high morbidity in other areas such as pediatric transplant surgery. Debates about whether thromboembolic events while on aspirin represent "aspirin resistance" or "high on-treatment platelet reactivity" persist, given the poor intertest agreement between testing platforms. PROCEDURE This prospective observational study involved measuring aspirin efficacy using ex vivo testing of platelet aggregation (VerifyNow-Aspirin, VN) and urine 11-dehydrothromboxane B2 (AsprinWorks, UTxB2) contemporaneously at up to three time points after major noncardiac organ transplant surgery. The collection days (CD) were the second and seventh days after stable aspirin dosing and then a convalescent time point 2-9 months later. RESULTS Fifty-five participants (age range, 0-21 years) were enrolled, having undergone total pancreatectomy with islet autotransplantation (N = 36), orthotopic liver transplantation (N = 18), and combined liver-kidney transplantation (N = 1). Platelet reactivity measured by VN remained unchanged, whereas UTxB2, which was elevated postoperatively, decreased significantly from CD1 to CD2 and CD3. Discordance in therapeutic efficacy was noted per manufacturer cutoffs, with therapeutic VN results in 86% of tests, whereas 12% of UTxB2 were therapeutic. Age-based stratification of UTxB2 results using previously published pediatric median levels increased overall UTxB2 therapeutic rates (80%) and intertest concordance (67% vs 27% if using adult range). No thrombotic events were observed. CONCLUSIONS Our data suggest that urine thromboxane production may be an underappreciated reflection of postoperative inflammation. Validation of pediatric normal ranges for UTxB2 is a critical next step.

Objectives Smoking and alcohol use are risk factors for acute and chronic pancreatitis, and their role on anxiety, depression, and opioid use in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT) is unknown. Methods We included adults enrolled in the Prospective Observational Study of TPIAT (POST). Measured variables included smoking (never, former, current) and alcohol abuse or dependency history (yes vs no). Using univariable and multivariable analyses, we investigated the association of smoking and alcohol dependency history with anxiety and depression, opioid use, and postsurgical outcomes. Results Of 195 adults studied, 25 were current smokers and 77 former smokers, whereas 18 had a history of alcohol dependency (of whom 10 were current smokers). A diagnosis of anxiety was associated with current smoking (P = 0.005), and depression was associated with history of alcohol abuse/dependency (P = 0.0001). However, active symptoms of anxiety and depression at the time of TPIAT were not associated with smoking or alcohol status. Opioid use in the past 14 days was associated with being a former smoker (P = 0.005). Conclusions Active smoking and alcohol abuse history were associated with a diagnosis of anxiety and depression, respectively; however, at the time of TPIAT, symptom scores suggested that they were being addressed.

Background While operational tolerance has been previously described in isolated intestinal transplant, reports of this phenomenon in combined liver-intestine transplant are lacking. Case description We detail a unique case of a patient who received a composite allograft including liver, pancreas, and small bowel due to short gut syndrome secondary to gastroschisis complicated by volvulus. The indication for transplantation was permanent dependence on total parenteral nutrition, end-stage liver disease, recurrent sepsis, and persistent stomal variceal hemorrhage. The patient developed severe graft-versus-host disease with grade 3 skin involvement, ophthalmic, and pulmonary involvement with 53% donor T-cell chimerism. She required aggressive therapy including high-dose methylprednisolone, rituximab, cyclophosphamide, and alemtuzumab. Due to infection concerns following depletion of her lymphocytes, immunosuppression was discontinued with close surveillance of her allograft. Nearly 10 years later, the patient has continued off all immunosuppression without evidence of rejection or graft dysfunction and demonstrates immunocompetence with normal functional immune assays and development of appropriate live vaccination titers. Conclusion This report of operational tolerance following pediatric composite liver-pancreas-intestine transplantation provides evidence that the complex immunologic balance in intestinal transplantation may on rare occasions favor immunosuppression reduction or even discontinuation. Future trials of immunosuppression minimization in this population may be warranted.

To evaluate the effect of intraoperative fluid type [half normal saline (0.45NS) or lactated Ringer's solution (LR)] on the risk of systemic inflammatory response syndrome (SIRS) and acute kidney injury after total pancreatectomy with islet autotransplantation in children.Retrospective review where demographics, operative details, systemic inflammatory response, and evaluation for end organ dysfunction over the first 5 postoperative days was obtained. Mixed effects Poisson regression compared risk of SIRS and acute kidney injury by intraoperative fluid type.Forty three patients were included with no difference in demographic characteristics between groups. SIRS was observed in 95, 77, and 71% over post operative days 1, 3, and 5. Intraoperative fluid type was found to not be associated with postoperative SIRS (RR: 0.91, p = 0.23). However, female sex (RR: 1.30, p 0.01), increased BMI (RR: 1.08, p 0.01), and longer operative time (RR: 1.07, p 0.01) were found to be factors that are associated with increased risk of postoperative SIRS. Intraoperative 0.45NS use was associated with increased acute kidney injury compared to LR on postoperative day 1 (52% vs 0%, p 0.01), but not on postoperative days 3 or 5.Intraoperative fluid type (0.45NS vs LR) does not increase the risk of postoperative SIRS in children after TPIAT. Predictive factors that are associated with an increased risk of eliciting postoperative SIRS includes female sex, increased BMI, and longer operative times.III.

Hyperglycemia is detrimental to postoperative islet cell survival in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT). This makes continuous glucose monitoring (CGM) a useful management tool. We evaluated the accuracy of the Dexcom G6 CGM in pediatric intensive care unit patients following TPIAT. Twenty-five patients who underwent TPIAT had Dexcom G6 glucose values compared to paired serum glucose values. All paired glucose samples were obtained within 5 minutes of each other during the first seven days post TPIAT. Data were evaluated using mean absolute difference (MAD), mean absolute relative difference (MARD), %20/20, %15/15 accuracy, and Clarke Error Grid analysis. Exclusions included analysis during the CGM “warm-up” period and hydroxyurea administration (known drug interference). A total of 183 time-matched samples were reviewed during postoperative days 2–7. MAD was 14.7 mg/dL and MARD was 13.4%, with values of 15.2%, 14.0%, 12.1%, 11.4%, 13.2% and 14.1% at days 2, 3, 4, 5, 6 and 7, respectively. Dexcom G6 had a %20/20 accuracy of 78%, and a %15/15 accuracy of 64%. Clarke Error Grid analysis showed that 77% of time-matched values were clinically accurate, and 100% were clinically acceptable. The Dexcom G6 CGM may be an accurate tool producing clinically acceptable values to make reliable clinical decisions in the immediate post-TPIAT period.

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples ( n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p ( P = 0.03), hsa-miR-148a-3p ( P = 0.04) and hsa-miR-221-3p ( P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p ( P = 0.04) and hsa-miR-7-5p ( P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p ( P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p ( P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg ( r = −0.20, P = 0.02). Also, hsa-miR-200c ( r = 0.18, P = 0.03) and hsa-miR-221-3p ( r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.

BACKGROUND: Congenital portosystemic shunt (CPSS) is a rare malformation in which splanchnic venous flow bypasses the liver. CPSS is associated with other congenital anomalies and syndromes and can be associated with life-threatening complications. CPSS and their management remain underreported in the literature. Here, we review the clinical characteristics, management, and outcomes of a cohort of children and young adults with CPSS from two pediatric centers. METHODS: Cases of CPSS from Cincinnati Children’s Hospital Medical Center and C.S. Mott Children’s Hospital were reviewed to define CPSS anatomy, associated anomalies, complications, interventions, and outcomes. The imaging features and histopathology of liver lesions were characterized in detail. RESULTS: A total of 11 cases were identified. Median age was 10 years (range 0–26); 8 (73%) cases were female. Associated anomalies included six patients with heterotaxy (55%), five patients with congenital heart disease (45%), three patients with Turner syndrome (27%), and two patients with omphalocele, exstrophy, imperforate anus, spinal defects (OEIS) complex (18%). Eight (73%) cases had hyperammonemia ± encephalopathy. A 4-month-old presented with hepatopulmonary syndrome, and 12-year-old presented with pulmonary hypertension. Eight patients (73%) had liver lesions including five with premalignant adenomas and three with well-differentiated hepatocellular carcinoma (HCC). Four children underwent successful CPSS occlusion/ligation. Three children underwent liver transplant (2) or resection (1) for HCC without recurrence at extended follow-up. CONCLUSIONS: CPSS is associated with multiple anomalies (heterotaxy, congenital heart disease) and syndromes (Turner syndrome). CPSS liver lesions should be very carefully evaluated due to risk of premalignant adenomas and HCC. Serious complications of CPSS can occur at a young age but can be managed endovascularly or with open surgery.

Objectives Megacystis–microcolon–hypoperistalsis syndrome (MMIHS) also called Berdon's Syndrome, is a smooth muscle myopathy that results in an enlarged bladder, microcolon, and small bowel hypoperistalsis. In our series of six patients with this disorder, all had disordered swallowing. Therefore, we prospectively characterized esophageal structure and function in all. Methods Diagnoses had been established by contrast radiography, small bowel manometry, and urodynamic studies. To investigate the esophagus, we endoscoped and biopsied the esophagus of each patient on multiple occasions. All patients also underwent water soluble contrast esophagography and esophageal manometry. Results Upon careful questioning, all patients had swallowing dysfunction, and the majority of their enteral intake was via gastrostomy or gastrojejunostomy. All took some oral alimentation, but eating was slow and none could aliment themselves completely by the oral route, receiving 50% or less of their calories by mouth. Four had megaesophagus whereas the esophagus of the two youngest was of normal caliber. All had eosinophilic esophagitis and/or esophageal Candidiasis from time to time, but successful treatment of these findings failed to improve their symptoms. Manometry revealed normal lower esophageal sphincter (LES) resting tone and normal LES relaxation, but for all, peristalsis was absent in the esophageal body. Conclusions This series expands the spectrum of findings in MMIHS, to include a primary motility disorder of the esophageal body. As patients age, the esophageal caliber appears to increase. Successful treatment of neither esophageal eosinophilia nor Candidiasis is effective in ameliorating the motility disorder. If our findings are confirmed in more patients with MMIHS, this disorder should be renamed, megacystis–microcolon–intestinal-and esophageal hypoperistalsis syndrome. Type of study Prognosis study, Level IV (case series).

Cystic fibrosis (CF) is a genetic disorder caused by defective CF Transmembrane Conductance Regulator (CFTR) function. Insulin producing pancreatic islets are located in close proximity to the pancreatic duct and there is a possibility of impaired cell-cell signaling between pancreatic ductal epithelial cells (PDECs) and islet cells as causative in CF. To study this possibility, we present an in vitro co-culturing system, pancreas-on-a-chip. Furthermore, we present an efficient method to micro dissect patient-derived human pancreatic ducts from pancreatic remnant cell pellets, followed by the isolation of PDECs. Here we show that defective CFTR function in PDECs directly reduced insulin secretion in islet cells significantly. This uniquely developed pancreatic function monitoring tool will help to study CF-related disorders in vitro, as a system to monitor cell-cell functional interaction of PDECs and pancreatic islets, characterize appropriate therapeutic measures and further our understanding of pancreatic function., Defective CFTR protein, responsible for Cystic Fibrosis (CF), is highly expressed in pancreatic ductal epithelial cells (PDECs) but their impact on insulin secreting pancreatic islets is not fully understood. Here the authors develop a non-CF and CF patient derived pancreas-on-a-chip model to study how CF affects insulin secretion.

Objective This study aims to explore the role of thrombopoietin (TPO) production in extreme thrombocytosis that is often observed after pancreatectomy with islet autotransplantation (IAT) and the effectiveness of hydroxyurea in thrombocytosis management. Methods Retrospective chart review was performed for all patients who underwent pancreatectomy with IAT at our institution between April 1, 2015, and December 31, 2016. Data evaluated included demographics, platelet counts, TPO levels, and thrombocytosis management strategies. Results Twelve total and 1 subtotal pancreatectomy with IAT cases were reviewed. All operations included splenectomy. No major surgical or thrombotic complications occurred. Thrombopoietin levels, normal preoperatively, rose significantly (median, 219 pg/mL) soon after surgery, peaking on median postoperative day 3. Platelet counts, also normal preoperatively, increased within a week of surgery, with 92% over 1000 K/μL (median peak platelet count, 1403 K/μL). Platelet counts and TPO levels dropped after hydroxyurea initiation in most patients. Conclusions After pancreatectomy with IAT, patients experienced marked TPO rise and subsequent thrombocytosis, and both decreased significantly after hydroxyurea initiation. These data suggest that TPO elevation and associated increased platelet production may be one driver of early extreme post-total pancreatectomy with islet autotransplantation thrombocytosis, and this process may be modulated by hydroxyurea.

Total pancreatectomy with islet autotransplantation (TPIAT) is used to treat debilitating chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) that has failed medical and endoscopic therapy. We performed a retrospective review of TPIAT patients at a free-standing children’s hospital to evaluate perioperative outcomes. Twenty patients (median age 13, 65% female) underwent TPIAT (2015 through 2017). Of the 20 patients, 95% had CP and 1 patient (5%) had ARP alone. Seventy-five percent of the patients had a pancreatitis-associated genetic mutation; 40% had pancreas divisum. The median surgical time was 757 (IQR 657 to 835) minutes. Median islet equivalents per kg of body weight (IEQ/kg) were 6404 (IQR 5018 to 7554). At 90 days postoperatively vs preoperatively, significantly fewer patients were receiving parenteral nutrition (0% vs 25%, P = .006) and opioids (45% vs 75%, P = .01). Short Form 36-Item Health Survey (SF-36) physical health module scores and total scores improved (34.0 preoperatively vs 54.6 at 90 days, P = .008, and 47.1 vs 65.3, P = .007, respectively); SF-10 physical health scores also improved (13.4 vs 33.1, P = .02). Insulin requirement decreased from 0.5 unit/kg/day to 0.4 unit/kg/day between discharge and 90 days (P = .02). TPIAT is an effective option when debilitating disease persists despite maximal medical and endoscopic therapy. Opioid, parenteral nutrition, and exogenous insulin use can successfully be weaned within 90 days after TPIAT, with gains in health-related quality of life.

The Pancreas Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition aims to promote awareness of pediatric pancreatic diseases, support clinical and basic science research in the field, educate pediatric gastroenterologists, and advocate on behalf of pediatric patients with pancreatic disorders. At the 2017 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Pancreas Committee held a full day symposium on pediatric pancreatic diseases, entitled, "Frontiers in Pediatric Pancreatology." The symposium served as a timely and novel academic meeting that brought together individuals with a vested interest in the care of children with pancreatic disorders. The objective of this day-long course was to update practicing gastroenterologists on the latest advances in research, management algorithms, endoscopic therapies, radiographic resources, surgical approaches, and novel drug therapies targeted to pediatric pancreatitis. Presentations were divided into 4 modules: diagnosis, risk factors, and natural history of pancreatitis; pancreatic imaging and exocrine function; management of pancreatitis; and new frontiers in pediatric pancreatitis research. The course fostered a unique ecosystem for interdisciplinary collaboration, in addition to promoting discussion and stimulating new research hypotheses regarding pediatric pancreatic disorders. Oral presentations by experts in various fields of pancreatology led to thought-provoking discussion; in addition, a meet-the-professor luncheon stimulated critical evaluation of current research in pediatric pancreatic diseases, highlighting knowledge gaps and future research endeavors. The current report summarizes the major learning points from this novel symposium focusing on the growing demographic of pediatric pancreatic diseases.

Biliary atresia is a newborn cholangiopathy that may lead to portopulmonary hypertension and cirrhosis-induced cardiomyopathy while awaiting liver transplantation. Extracorporeal life support and hepatic toxin filtration are life-saving interventions that provide cardiopulmonary support and hepatic dialysis to allow resolution of a child's illness. We utilized a combination of these extreme measures to bridge an infant with biliary atresia to transplantation. We reviewed cases of extracorporeal life support utilization in transplantation recipients in the Extracorporeal Life Support Organization database and determined that ours was the only use of pretransplant extracorporeal life support in biliary atresia.

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: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation. METHODS: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n=84) with adults (n=195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP. RESULTS: Children more commonly underwent splenectomy (100% versus 91%, p=0.002), pylorus preservation (93% versus 67%; p

Objectives Pancreas divisum (PD) is a risk factor in children for the development of acute pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy (mPES) may be of clinical benefit, however, the clinical outcomes from endotherapy remain unclear. We sought to review the outcomes and safety of therapeutic ERCP in children with PD. Methods We performed a retrospective chart of children with PD who underwent an ERCP between February 2012 and December 2018. Pertinent patient, clinical and procedure information was collected including procedure-related adverse events. A follow-up questionnaire of the parent was conducted to determine the clinical impact from endotherapy. Results Fifty-eight ERCPs were performed in 27 patients (14 boys; mean age: 9.7 years, range 2-19) with PD. All patients underwent a successful mPES. A genetic variant was identified in 19/26 (73%) tested patients. Post-ERCP pancreatitis (PEP) was the only observed adverse event; 21% (12/58). Median follow-up interval from first ERCP intervention to questionnaire completion was 31.5 months (range: 4--72 months). Of the 20 questionnaire responders, 13 reported clinical improvement from endotherapy. Conclusions The majority of children from our PD cohort possessed at least 1 genetic variant. Most questionnaire responders had a favorable response to endotherapy. PEP rate was comparable with that of prior reports in adult patients.

BACKGROUND: Chronic pancreatitis (CP) is associated with poor quality of life. Total pancreatectomy with islet autotransplantation (TPIAT) has traditionally been reserved for patients with refractory disease. We hypothesized TPIAT would lead to decreased costs and resource utilization after operation in children. METHODS: Retrospective review of 39 patients who underwent TPIAT at a single children’s hospital was performed. All inpatient admissions, imaging, endoscopic procedures, and operations were recorded for the year prior to and following operation. Costs were determined from Centers for Medicare and Medicaid Services. RESULTS: Median hospital admissions before operation was 5 (IQR:2–7) and decreased to 2 (IQR:1–3) after (p < 0.01). Median total cost for the year before operation was $36,006 (IQR:$19,914-$47,680), decreasing to $24,900 postoperatively (IQR:$17,432-$44,005, p = 0.03). Removing cost of TPIAT itself, total cost was further reduced to $10,564 (IQR:$3096-$29,669, p < 0.01). CONCLUSION: In children with debilitating CP, TPIAT has favorable impact on cost reduction, hospitalizations, and invasive procedures. Early intervention at a specialized pancreas center of excellence should be considered to decrease future resource utilization and costs among children.

Background Predicting post-operative glycemic control in children undergoing total pancreatectomy with islet autotransplantation (TPIAT) remains difficult. The purpose of our study was to explore preoperative imaging as a marker for islet yield and insulin need in pediatric patients undergoing TPIAT. Methods This was a retrospective study of children (≤18 years) who had undergone TPIAT between April 2015 and December 2018 and had 6 or more months of post-TPIAT follow-up. Patient specific factors (height, weight, body mass index [BMI], body surface area [BSA]) and pancreas volume segmented from the most recent pre-operative cross-sectional imaging were explored as predictors of islet yield (total islet counts [TIC], total islet equivalents [TIE], islet equivalents per kilogram body weight [IEQ/kg]) and glycemic control (total daily dose of insulin per kilogram body weight [TDD/kg], insulin independence) using Pearson correlation and univariate and multiple regression. Results Thirty-three patients, median age 13 years (IQR: 10–15 years), 64% female (21/33) met inclusion criteria. Nine patients (27%) achieved insulin independence at six months. Median TIE isolated was 310,000 (IQR: 200,000–460,000). Segmented pancreas volume was moderately associated with TIE (coefficient estimate = 0.34, p = 0.034). On multiple regression analysis, there was no significant predictor of insulin independence but number of attacks of pancreatitis (estimate = 0.024; p = 0.018) and segmented pancreas volume by body weight (estimate = −0.71; p Conclusion Pancreas volume segmented from pre-TPIAT imaging has predictive performance for post-TPIAT insulin need in children.

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

This paper aims to provide an overview of islet cell transplantation in children, with specific attention to pediatric total pancreatectomy with islet autotransplantation (TPIAT). We will summarize the definition and causes of chronic pancreatitis in children, the TPIAT procedure and potential complications, the process of islet cell isolation and autotransplantation, and long-term results after TPIAT. Lastly, we will briefly discuss islet cell allotransplantation in the adult population and its potential role in treating children.

Background/objectives Drug induced acute pancreatitis (DIAP) as one of the acute pancreatitis (AP) risks factors is a poorly understood entity. The aim of the current study was to compare the characteristics and course of DIAP cases in children presenting with a first attack of AP. Methods Patients presenting with AP were included in a prospective database. We enrolled 165 AP patients that met criteria for inclusion. DIAP patients were included in that group if they were exposed to a drug known to be associated with AP and the rest were included in the non-drug induced-acute pancreatitis (non-DIAP) group. Results DIAP was observed in 40/165 (24%) of cases, 24 cases had drug-induced as the sole risk factor, and 16 had DIAP with another risk factor(s). The two groups were similar in intravenous fluid and feeding managements, but ERCP was more commonly performed in the non- DIAP group, 14 (11%), vs 0% in the DIAP group, p = 0.02. Moderately severe [9 (23%) vs 11 (9%)] and severe AP [7 (18%) vs 6 (5%)] were more commonly associated with DIAP than non- DIAP, p = 0.001. DIAP was more commonly associated with ICU stay, 10 (25%), vs 12 (10%), p = 0.01, hospital stay was longer in DIAP median (IQR) of 6 (3.9–11) days vs 3.3 (2–5.7) days in non- DIAP, p = 0.001. The DIAP group had a significantly higher proportion of comorbidities (p Conclusions DIAP is a leading risk factor for a first attack of AP in children and is associated with increased morbidity and severity of the pancreatitis course. DIAP warrants further investigation in future studies.

Objective: To assess the degree, duration, and mean absolute relative difference (MARD) of false values per continuous glucose monitoring (CGM) systems when hydroxyurea (HU) is administered. Research Design and Methods: Inpatient glucometer and CGM data from 16 post-total pancreatectomy (TPIAT) patients using Dexcom Professional G4 and 6 patients using Dexcom G6 were analyzed after daily dosing with HU. Timing of HU dosing and up to 2 weeks of sensor and glucometer values were assessed in each patient. Results: A false elevation (>20 mg/dL) of sensor readings were identified after HU dosing. The greatest discrepancy between glucometer and sensor readings occurred 0.5-2 hours after HU administration [G4 (mean 53 mg/dL, median 44 mg/dL, MARD 0.55), G6 (mean 67 mg/dL, median 72.5 mg/dL, MARD 0.79)]. The sensor and glucometer readings were Conclusions: There is a false elevation of sensor glucose readings compared to glucometer values (up to 180 mg/dL (G4), 235 mg/dL (G6)) from 0.5hr to 6hr following HU administration. It is important to counsel a patient using a Dexcom CGM system and HU therapy on this finding and to advise reliance on glucometer testing for accurate glucose assessment up to 6 hours after HU administration. Disclosure S.E. Tellez: None. L. Hornung: None. J.D. Courter: None. M. Abu-El-Haija: None. J.D. Nathan: None. S. Lawson: None. D.A. Elder: None.

Objective: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure for patients with chronic pancreatitis who experience debilitation and poor quality of life. Glucose targets are critical for islet survival. We hypothesized that early transition from intravenous insulin to insulin pump therapy would improve glucose control and impact hospital duration. Research Design and Methods: We performed a retrospective analysis of 40 patients who underwent TPIAT. Prior to 2016, post-operative insulin was delivered intravenously and transitioned to multiple daily injections (MDI) followed by pump administration (n=14). After 2016, post-operative insulin was delivered intravenously followed by early transition to pump therapy (n=26). Outcomes analyzed between groups included: percentage of blood glucoses in target (80-120 mg/dL), hypoglycemia (140 mg/dL), blood glucose variability, and length of stay after transition off intravenous insulin. Results: Patients with early transition to pump therapy had a higher proportion of glucose values in target range (p=0.0003), a lower proportion of hyperglycemia (p=0.04), and a lower proportion of hypoglycemia, though not significant (p=0.33). In patients with early pump transition, variability in glucose values decreased over the first 10 days post-intravenous insulin (p=0.001) and post-transition median length of stay was shorter by 5 days (p=0.005). Conclusions: Early pump therapy in this population achieved tighter glycemic control and reduced duration of stay. Disclosure S.E. Tellez: None. L. Hornung: None. J.D. Courter: None. M. Abu-El-Haija: None. J.D. Nathan: None. S. Lawson: None. D.A. Elder: None.

Total pancreatectomy with islet autotransplantation (TPIAT) can effectively improve pain and functional impairment associated with chronic pancreatitis (CP) in children. However, children undergoing this procedure usually develop post-pancreatectomy diabetes and require chronic insulin therapy. It can be difficult for providers and patients to conceptualize trading the symptoms of CP for the burden of diabetes. Therefore, we sought to evaluate diabetes-related quality of life (QOL) over time in children who underwent TPIAT, and compare QOL scores post-TPIAT with children who have type 1 diabetes (T1D). The Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module was used to assess diabetes-related QOL. PedsQL scores were evaluated in 46 children (0.2). The Total PedsQL score, mostly attributable to the Diabetes Symptoms subscale, decreased over time in patients who underwent TPIAT. Additionally, diabetes-related QOL at 24 months was not significantly different from children with T1D. This data may be used to help counsel families who are considering TPIAT for treatment of CP. Disclosure J.M. Redel: None. L. Hornung: None. D.A. Elder: None. J.D. Nathan: None. M. Abu-El-Haija: None. Funding Cincinnati Children’s Hospital

Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate pain and mitigate diabetes in patients with chronic pancreatitis when medical/endoscopic therapies have failed. Predictors of insulin independence and graft function have not been well studied in pediatric TPIAT patients. Our aim was to evaluate predictors of insulin requirement at one year post-TPIAT. This was a retrospective review of 35 patients ( Disclosure S. Swauger: None. L. Hornung: None. D.A. Elder: None. J.D. Nathan: None. M. Abu-El-Haija: None.

Background Hepatocellular carcinoma (HCC) is often a chemoresistant neoplasm with a poor prognosis. Pediatric HCC may reflect unique biological and clinical heterogeneity. Procedure An IRB-approved retrospective institutional review of patients with HCC treated between 2004 and 2015 was undertaken. Clinical, radiographic, and histologic data were collected from all patients. Results Thirty-two patients with HCC, median age 11.5 years (range 1-20) were identified. Seventeen patients had a genetic or anatomic predisposition. Histology was conventional HCC (25) and fibrolamellar HCC (7). Evans staging was 1 (12); 2 (1); 3 (10); 4 (9). Sixteen patients underwent resection at diagnosis and five patients after neoadjuvant chemotherapy. Surgical procedures included liver transplantation (LT, 11), hemihepatectomy (9), and segmentectomy (1). Eighteen patients had medical therapy (13 neoadjuvant, 5 adjuvant). Most common initial medical therapy included sorafenib alone (7) and cisplatin/doxorubicin-based therapy (8). Overall, 14 (43.8%) patients survived with a median follow-up of 58.8 months (range 26.5-157.6). Cause of death was most often linked to lack of primary tumor surgery (11). Of the survivors, Evans stage was 1 (11), 2 (1), and 3 (2, both treated with LT). Four of 18 patients (22%) who received medical therapy, 8 of 17 patients with a predisposition (47%), and 14 of 21 patients (66%) who underwent surgery remain alive. Conclusions Genetic and anatomic predisposing conditions were seen in over half of this cohort. Evans stage 1 or 2 disease was linked to improved survival. LT trended toward improved survival. Use of known chemotherapy agents may benefit a smaller group of pediatric HCC and warrants formal prospective study through cooperative group trials.

Background Advances in our understanding of total pancreatectomy with islet autotransplantation (TPIAT) have been made. We aimed to define indications and outcomes of TPIAT. Methods Expert physician-scientists from North America, Asia, and Europe reviewed the literature to address six questions selected by the writing group as high priority topics. A consensus was reached by voting on statements generated from the review. Results Consensus statements were voted upon with strong agreement reached that (Q1) TPIAT may improve quality of life, reduce pain and opioid use, and potentially reduce medical utilization; that (Q3) TPIAT offers glycemic benefit over TP alone; that (Q4) the main indication for TPIAT is disabling pain, in the absence of certain medical and psychological contraindications; and that (Q6) islet mass transplanted and other disease features may impact diabetes mellitus outcomes. Conditional agreement was reached that (Q2) the role of TPIAT for all forms of CP is not yet identified and that head-to-head comparative studies are lacking, and that (Q5) early surgery is likely to improve outcomes as compared to late surgery. Conclusions Agreement on TPIAT indications and outcomes has been reached through this working group. Further studies are needed to answer the long-term outcomes and maximize efforts to optimize patient selection.

OBJECTIVES To utilize a Luminex platform to examine multiple cytokines simultaneously as well as clinical laboratory testing to identify markers that predict acute pancreatitis severity in the pediatric population on admission. STUDY DESIGN Patients (

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure for patients with chronic pancreatitis and poor quality of life. Euglycemia is critical for islet cell survival and engraftment. We reviewed clinical care practice and hypothesized that early in-hospital transition from intravenous insulin to insulin pump therapy, managed by an endocrine unit trained on post-surgical care, would improve glucose control and impact the length of hospital stay. We completed a retrospective analysis of 40 pediatric patients who underwent TPIAT. Comparative hospitalized postoperative groups included those who received insulin intravenously, followed by multiple daily injections, subsequently managed by pump therapy (n = 14), versus those who received insulin intravenously followed by early pump therapy provided on the endocrine unit trained to manage post-surgical patients (n = 26). The outcomes analyzed included percentage of blood glucoses in target (4.44–6.66 mmol/L (80–120 mg/dL)), hypoglycemia (&lt, 3.33 mmol/L (&lt, 60 mg/dL)) and hyperglycemia (&gt, 7.77 mmol/L (&gt, 140 mg/dL)), blood glucose variability, and length of hospital unit stay post-ICU. Hospitalized patients with early transition to pump therapy on a specialized endocrine unit had a higher proportion of glucose values in the target range (61% vs. 51%, p = 0.0003), a lower proportion of hyperglycemia (15% vs. 19%, p = 0.04), and a lower proportion of hypoglycemia, though not statistically significant (3.4% vs. 4.4%, p = 0.33). Early pump users also had lower variability in glucose values over 10 days post-intravenous insulin (p = 0.001), and the post-transition median length of stay was shorter by 5 days (median: 11.5 vs. 16.5 days, p = 0.005). Early in-hospital pump therapy managed by the specialized endocrine unit improved glucose outcomes and reduced the duration of in-unit stay.

Background Choledochoceles may cause biliary obstruction and harbor malignancy. We conducted a 40-year systematic review of the literature for this rare anomaly. Methods PubMed and Cochrane databases were accessed 1975–2015 using terms “choledochocele” or “choledochal cyst”. Studies reviewed that met the following criteria: English language, published 1975–2015 with human subjects. Results 325 patients with a choledochocele were identified, including 71 case reports and 254 cases within institutional reviews. 13 pediatric case reports of choledochocele exist, with abdominal pain being the most common symptom (n = 11). The most frequent diagnostic and treatment modalities were ultrasound (n = 10), and endoscopic sphincterotomy (n = 5). No malignancies were reported. 58 adult case reports exist, with the most common presenting symptom being abdominal pain (n = 54). Ultrasound was the frequently employed diagnostic modality (n = 32). Open procedures were performed more often (n = 30). Malignant lesions were identified in 5. In 42 institutional reviews, the frequency of choledochocele was 0.7%. Of those for whom treatment was reported, 69% underwent endoscopic sphincterotomy. Conclusion Choledochocele is a rare malformation. Similarities exist between pediatric and adult patients, but malignancy has only been reported in adults. An algorithm based on patient age, cyst size, lining and amenability to endoscopic resection may be considered as a treatment strategy for this uncommon condition.

Summary Hepatocellular adenomas (HCA) are benign tumours with potential for malignant transformation with no recommendations regarding management in the paediatric population. We report a case of an inflammatory adenoma with β-catenin activated pathway in an obese, paediatric patient with nonalcoholic steatohepatitis (NASH).Case Report: An 11-year-old female presented with a microlobulated liver lesion measuring >5 cm in magnetic resonance imaging (MRI) with inflammatory adenoma with β-catenin activated pathology arising in a background of NASH, nonalcoholic fatty liver disease (NAFLD) activity score 5/8. Imaging follow-up demonstrated stable disease without progression for 3 years.Discussion: Malignant transformation of Hepatocellular adenomas in a child is approximately 4.2%. It is unknown if hepatic steatosis increases this risk. Obese patients mainly develop inflammatory and β-catenin activated (highest risk for malignant transformation) adenomas. Our patient had inflammatory and β-catenin activation, which led to monitoring for malignant transformation.Conclusion: We report a β-catenin activated inflammatory adenoma in a child with obesity and NASH with ongoing expectant management.

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

Objective The natural course of patients who develop acute pancreatitis (AP) can range from mild to severe acute pancreatitis (SAP). The aim of this study was to evaluate for early predictors of developing SAP during the first episode of AP in a prospective pediatric cohort. Methods Clinical data were prospectively collected and subsequently analyzed for pediatric patients presenting with their first episode of AP between March 2013 and January 2017 to Cincinnati Children's Hospital Medical Center. Results A total of 118 patients were included in the analysis, and 22 (18.6%) developed SAP. Patients who developed SAP had significantly higher values of blood urea nitrogen (BUN) (P = 0.007), magnesium (P = 0.04), glucose (P = 0.03), sodium (P = 0.03), and C-reactive protein (P = 0.02). A logistic regression model with BUN as a predictor of SAP was superior to any other combination of variables (area under the receiver operating characteristic curve, 0.75; 95% confidence interval, 0.61-0.89; sensitivity, 63%; specificity, 81%; positive predictive value, 43%; negative predictive value, 91%). Conclusions This study generated a predictive model using elevated BUN as a significant predictor of SAP. The findings are useful for early identification of pediatric patients at higher risk of developing SAP.