Publications by authors named "Jaimie D Nathan"

73 Publications

Total pancreatectomy with islet autotransplantation reduces resource utilization in pediatric patients.

Am J Surg 2021 Jan 27. Epub 2021 Jan 27.

Cincinnati Children's Hospital Medical Center, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH, USA; University of Cincinnati Medical Center, Department of Surgery, Cincinnati, OH, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.amjsurg.2021.01.030DOI Listing
January 2021

Imaging prediction of islet yield and post-operative insulin requirement in children undergoing total pancreatectomy with islet autotransplantation.

Pancreatology 2021 Jan 5;21(1):269-274. Epub 2020 Dec 5.

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

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 < 0.001) were significant predictors of insulin TDD/kg.

Conclusion: Pancreas volume segmented from pre-TPIAT imaging has predictive performance for post-TPIAT insulin need in children.
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http://dx.doi.org/10.1016/j.pan.2020.12.004DOI Listing
January 2021

Preoperative ERCP has no impact on islet yield following total pancreatectomy and islet autotransplantation (TPIAT): Results from the Prospective Observational Study of TPIAT (POST) cohort.

Pancreatology 2021 Jan 24;21(1):275-281. Epub 2020 Nov 24.

University of Minnesota Minneapolis, MN, USA.

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 < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement.

Conclusions: ERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.
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http://dx.doi.org/10.1016/j.pan.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924984PMC
January 2021

Inaccurate Glucose Sensor Values After Hydroxyurea Administration.

Diabetes Technol Ther 2020 Dec 30. Epub 2020 Dec 30.

Division of Endocrinology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

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. 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. 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 <1.1 mmol/L, mean (-0.5 mmol/L) and median (-0.5 mmol/L), MARD 14% (G4) and <1.1 mmol/L, mean (0.3 mmol/L) and median (0.3 mmol/L), MARD 17% (G6), by 6 h after administration. Error analysis with the G6 system found 94% of pairs in clinically acceptable range by 6-9 h after HU administration. Aspirin, also given once daily, did not result in glucose value discrepancy with the G6 system but variability was observed with the G4 system. There was marked elevation of sensor glucose readings compared with glucometer values [up to 13.9 mmol/L (G4), 13 mmol/L (G6)] from 0.5 to 6 h after 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 6-9 h after HU administration.
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http://dx.doi.org/10.1089/dia.2020.0490DOI Listing
December 2020

Clinical Outcomes Following Therapeutic Endoscopic Retrograde Cholangiopancreatography in Children With Pancreas Divisum.

J Pediatr Gastroenterol Nutr 2021 Feb;72(2):300-305

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center.

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.
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http://dx.doi.org/10.1097/MPG.0000000000002996DOI Listing
February 2021

Hydroxyurea Pharmacokinetics in Pediatric Patients After Total Pancreatectomy With Islet Autotransplantation.

J Clin Pharmacol 2020 Oct 7. Epub 2020 Oct 7.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Total pancreatectomy with islet autotransplantation is a complex surgical approach for acute recurrent or chronic pancreatitis that frequently triggers extreme thrombocytosis (platelets ≥ 1000 × 10 /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.
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http://dx.doi.org/10.1002/jcph.1759DOI Listing
October 2020

Natural Course of Pediatric Portal Hypertension.

Hepatol Commun 2020 Sep 16;4(9):1346-1352. Epub 2020 Jul 16.

Division of Pediatric General and Thoracic Surgery Cincinnati Children's Hospital Medical Center Cincinnati OH.

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%;  < 0.01). Surgical interventions differed based on etiology ( < 0.01), with IH more likely resulting in a transplant only (65%) and EH more likely to result in a shunt only (43%); 30% of patients with IH and 47% of patients with EH did not undergo an intervention for pHTN. Kaplan-Meier analysis revealed a significant increase in mortality in the group that received no intervention compared to shunt, transplant, or both and lower mortality in patients with prehepatic pHTN compared to other etiologies ( < 0.01 each). Multivariate analysis revealed increased odds of mortality in patients with refractory ascites (odds ratio [OR], 4.34; 95% confidence interval [CI], 1.00, 18.88;  = 0.05) and growth failure (OR, 13.49; 95% CI, 3.07, 58.99;  < 0.01). In this single institution study, patients with prehepatic pHTN had better survival and those who received no intervention had higher mortality than those who received an intervention. Early referral to specialized centers with experience managing these complex disease processes may allow for improved risk stratification and early intervention to improve outcomes.
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http://dx.doi.org/10.1002/hep4.1560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471417PMC
September 2020

Drug induced pancreatitis is the leading known cause of first attack acute pancreatitis in children.

Pancreatology 2020 Sep 24;20(6):1103-1108. Epub 2020 Jul 24.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

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 < 0.0001).

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.
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http://dx.doi.org/10.1016/j.pan.2020.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492485PMC
September 2020

The Role of Psychology in the Care of Children With Pancreatitis.

Pancreas 2020 08;49(7):887-890

Children with acute recurrent and chronic pancreatitis experience severe abdominal pain that may be intermittent or chronic. Pain is often debilitating, causing interference with academic, social, family, and extracurricular activities that are important to youth. Disruption of these routines and the unpredictability of pain flares place children with pancreatitis at increased risk for development of anxious or depressive symptoms. Pediatric psychologists trained in cognitive-behavioral treatment are well suited to intervene on functional disability and mood disturbance, as well as teach coping skills. In an era where there is movement away from opioids, nonpharmacological strategies have an important place for pain management. In fact, positive outcomes following for children with other recurrent abdominal pain syndromes have been reported for this evidence-based intervention. In addition to pain management, pediatric psychologists can address other co-occurring behavioral and emotional problems in children with pancreatitis, such as needle phobia and poor adherence to the prescribed medical regimen.
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http://dx.doi.org/10.1097/MPA.0000000000001598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371256PMC
August 2020

Islet cell transplantation in children.

Semin Pediatr Surg 2020 Jun 23;29(3):150925. Epub 2020 May 23.

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH. Electronic address:

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.
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http://dx.doi.org/10.1016/j.sempedsurg.2020.150925DOI Listing
June 2020

Who's at Risk? A Prognostic Model for Severity Prediction in Pediatric Acute Pancreatitis.

J Pediatr Gastroenterol Nutr 2020 10;71(4):536-542

Division of Gastroenterology, Hepatology and Nutrition.

Objectives: The aim of the study was to validate and optimize a severity prediction model for acute pancreatitis (AP) and to examine blood urea nitrogen (BUN) level changes from admission as a severity predictor.

Study Design: Patients from 2 hospitals were included for the validation model (Children's Hospital of the King's Daughters and Children's National Hospital). Children's Hospital of the King's Daughters and Cincinnati Children's Hospital Medical Center data were used for analysis of BUN at 24 to 48 hours.

Results: The validation cohort included 73 patients; 22 (30%) with either severe or moderately severe AP, combined into the all severe AP (SAP) group. Patients with SAP had higher BUN (P = 0.002) and lower albumin (P = 0.005). Admission BUN was confirmed as a significant predictor (P = 0.005) of SAP (area under the receiver operating characteristic [AUROC] 0.73, 95% confidence interval [CI] 0.60-0.86). Combining BUN (P = 0.005) and albumin (P = 0.004) resulted in better prediction for SAP (AUROC 0.83, 95% CI 0.72-0.94). A total of 176 AP patients were analyzed at 24-48 hours; 39 (22%) met criteria for SAP. Patients who developed SAP had a significantly higher BUN (P < 0.001) after 24 hours. Elevated BUN levels within 24 to 48 hours were independently predictive of developing SAP (AUROC: 0.76, 95% CI: 0.66-0.85). Patients who developed SAP had a significantly smaller percentage decrease in BUN from admission to 24 to 48 hours (P = 0.002).

Conclusion: We externally validated the prior model with admission BUN levels and further optimized it by incorporating albumin. We also found that persistent elevation of BUN is associated with development of SAP. Our model can be used to risk stratify patients with AP on admission and again at 24 to 48 hours.
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http://dx.doi.org/10.1097/MPG.0000000000002807DOI Listing
October 2020

The role of total pancreatectomy with islet autotransplantation in the treatment of chronic pancreatitis: A report from the International Consensus Guidelines in chronic pancreatitis.

Pancreatology 2020 Jun 14;20(4):762-771. Epub 2020 Apr 14.

Department of Surgery, University of Minnesota Medical Center, Minneapolis, MN, USA; Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.pan.2020.04.005DOI Listing
June 2020

Clinical heterogeneity of pediatric hepatocellular carcinoma.

Pediatr Blood Cancer 2020 06 19;67(6):e28307. Epub 2020 Apr 19.

Division of Pediatric Hematology/Oncology, University of Illinois College of Medicine at Peoria, Peoria, Illinois.

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.
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http://dx.doi.org/10.1002/pbc.28307DOI Listing
June 2020

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

J Pediatr Gastroenterol Nutr 2020 07;71(1):112-118

Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE.

Objective: 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.

Study Design: 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.

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1097/MPG.0000000000002661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305964PMC
July 2020

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).

Contemp Clin Trials 2020 01 19;88:105898. Epub 2019 Nov 19.

University of Iowa, Stead Family Children's Hospital, Iowa City, IA, USA.

Introduction: Abdominal 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.

Methods: This 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.

Conclusions: This 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.
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http://dx.doi.org/10.1016/j.cct.2019.105898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952537PMC
January 2020

Sterility Cultures Following Pancreatectomy with Islet Autotransplantation in the Pediatric Population: Do They Matter?

J Gastrointest Surg 2020 Nov 19;24(11):2526-2535. Epub 2019 Nov 19.

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2023, Cincinnati, OH, 45229, USA.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.
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http://dx.doi.org/10.1007/s11605-019-04413-8DOI Listing
November 2020

Extreme Thrombocytosis after Pediatric Pancreatectomy with Islet Autotransplantation Is Unique Compared to Other Postsplenectomy States.

J Pediatr Surg 2020 Aug 25;55(8):1645-1650. Epub 2019 Oct 25.

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA, 54229; Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA, 54229; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA, 54229. Electronic address:

Background: 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.

Study Design: 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.

Results: 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.

Conclusions: 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.

Level-of-evidence Rating: Treatment study, Level III (retrospective comparative study).
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http://dx.doi.org/10.1016/j.jpedsurg.2019.09.019DOI Listing
August 2020

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.

J Pediatr Gastroenterol Nutr 2019 11;69(5):599-606

University of Iowa, Iowa City, IA.

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.
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http://dx.doi.org/10.1097/MPG.0000000000002482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834233PMC
November 2019

A Study on the Effect of Patient Characteristics, Geographical Utilization, and Patient Outcomes for Total Pancreatectomy Alone and Total Pancreatectomy With Islet Autotransplantation in Patients With Pancreatitis in the United States.

Pancreas 2019 10;48(9):1204-1211

From the Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH.

Objectives: A selective therapy for pancreatitis is total pancreatectomy and islet autotransplantation. Outcomes and geographical variability of patients who had total pancreatectomy (TP) alone or total pancreatectomy with islet autotransplantation (TPIAT) were assessed.

Methods: Data were obtained from the Healthcare Cost and Utilization Project National Inpatient Sample database. Weighed univariate and multivariate analyses were performed to determine the effect of measured variables on outcomes.

Results: Between 2002 and 2013, there were 1006 TP and 825 TPIAT in patients with a diagnosis of chronic pancreatitis, and 1705 TP and 830 TPIAT for any diagnosis of pancreatitis. The majority of the TP and TPIAT were performed in larger urban hospitals. Costs were similar for TP and TPIAT for chronic pancreatitis but were lower for TPIAT compared with TP for any type of pancreatitis. The trend for TP and TPIAT was significant in all geographical areas during the study period.

Conclusions: There is an increasing trend of both TP and TPIAT. Certain groups are more likely to be offered TPIAT compared with TP alone. More data are needed to understand disparities and barriers to TPIAT, and long-term outcomes of TPIAT such as pain control and glucose intolerance need further study.
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http://dx.doi.org/10.1097/MPA.0000000000001405DOI Listing
October 2019

Congenital Portosystemic Shunts in Children: Associations, Complications, and Outcomes.

Dig Dis Sci 2020 04 23;65(4):1239-1251. Epub 2019 Sep 23.

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, MLC 2023, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.

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.
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http://dx.doi.org/10.1007/s10620-019-05834-wDOI Listing
April 2020

Total pancreatectomy with islet autotransplantation in a pancreatic-sufficient cystic fibrosis patient.

J Cyst Fibros 2019 09 13;18(5):e53-e55. Epub 2019 Aug 13.

Div of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.

For children with Cystic Fibrosis (CF) suffering from acute recurrent pancreatitis (ARP), abdominal pain can be severe, difficult to treat, impair their quality of life, affect participation at school, and can lead to chronic opioid dependence. Total pancreatectomy with islet autotransplantation (TPIAT) is an uncommon treatment that is reserved for refractory cases of ARP. We present a case of a 4 year old female with pancreatic-sufficient CF, refractory ARP, frequent hospital admissions for abdominal pain, and continued growth failure despite gastrostomy tube and parenteral nutrition. One year after successful TPIAT, the patient is insulin-independent, growing well, and has not been re-hospitalized for abdominal pain. To our knowledge, this is the youngest patient with CF to undergo TPIAT for debilitating ARP. With CFTR modulators restoring some pancreatic function, CF clinicians should have increased vigilance for the development of ARP.
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http://dx.doi.org/10.1016/j.jcf.2019.07.009DOI Listing
September 2019

Sensitivity of Biochemical and Imaging Findings for the Diagnosis of Acute Pancreatitis in Children.

J Pediatr 2019 10 6;213:143-148.e2. Epub 2019 Aug 6.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address:

Objective: To determine the diagnostic sensitivity of serum biomarkers and imaging in the diagnosis of acute pancreatitis in children.

Study Design: This was a cross-sectional analysis of prospective registry data for children (age <21 years) whose first documented attack of acute pancreatitis occurred between March 2013 and October 2016 at a single-institution, tertiary care center. Main outcome was sensitivity of serum biomarkers and of imaging modalities, measured via descriptive statistics.

Results: In total, 112 children met the criteria for acute pancreatitis; 57 (51%) were male with a median age of 13.4 years (IQR 9.3-15.8 years). Serum amylase and lipase levels were obtained in 85 (76%) and 112 (100%) patients, respectively. Imaging was performed in 98 (88%) patients, with abdominal ultrasound (US) performed in 84 (75%) and computed tomography and/or magnetic resonance imaging performed in 46 (41%) patients. Fifty-three (47%) patients met all 3 diagnostic criteria (clinical, biochemical, and imaging) for acute pancreatitis. Laboratory testing had a 5.4% false-negative rate for acute pancreatitis. Serum lipase alone and amylase alone were 95% (95% CI 89%-98%) and 39% (95% CI 28%-50%) sensitive for acute pancreatitis, respectively. Imaging (any modality) was 61% sensitive (95% CI 51%-71%) for acute pancreatitis with a 34% false-negative rate. US alone was 52% (95% CI 41%-63%) sensitive for acute pancreatitis and computed tomography/magnetic resonance imaging was 78% (95% CI 63%-89%) sensitive. Combinations of diagnostic criteria performed no better than laboratory testing alone.

Conclusions: The majority of children coming to medical attention with their first documented occurrence of acute pancreatitis have characteristic symptoms. Serum lipase is highly sensitive for the diagnosis of acute pancreatitis, and serum amylase is moderately sensitive. Imaging, particularly US, is only moderately sensitive, and cross-sectional imaging provides greater sensitivity for diagnosing acute pancreatitis.
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http://dx.doi.org/10.1016/j.jpeds.2019.06.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765403PMC
October 2019

Patient-derived pancreas-on-a-chip to model cystic fibrosis-related disorders.

Nat Commun 2019 07 16;10(1):3124. Epub 2019 Jul 16.

Department of Pediatrics, Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

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.
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http://dx.doi.org/10.1038/s41467-019-11178-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635497PMC
July 2019

The role of surgical shunts in the treatment of pediatric portal hypertension.

Surgery 2019 11 5;166(5):907-913. Epub 2019 Jul 5.

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Surgery, University of Cincinnati, Cincinnati, OH. Electronic address:

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.
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http://dx.doi.org/10.1016/j.surg.2019.05.009DOI Listing
November 2019

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

J Pediatr Gastroenterol Nutr 2019 08;69(2):206-211

University of Iowa Stead Family Children's Hospital, Iowa City, IA.

Objective: 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.

Study Design: Data were collected from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) cohort. Kaplan-Meier curves were constructed to calculate duration of progression from initial attack of acute pancreatitis (AP) to CP. Log-rank test was used to compare survival (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.

Results: 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%).

Conclusions: 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.
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http://dx.doi.org/10.1097/MPG.0000000000002405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699635PMC
August 2019

Thrombopoietin Contributes to Extreme Thrombocytosis After Pediatric Pancreatectomy With Islet Autotransplantation.

Pancreas 2019 May/Jun;48(5):652-655

Division of Hematology, and.

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.
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http://dx.doi.org/10.1097/MPA.0000000000001313DOI Listing
February 2020

Chronic Pancreatitis: Pediatric and Adult Cohorts Show Similarities in Disease Progress Despite Different Risk Factors.

J Pediatr Gastroenterol Nutr 2019 04;68(4):566-573

Department of Medicine.

Objectives: The 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.

Methods: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.

Results: Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, P = 0.011).

Conclusions: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.
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http://dx.doi.org/10.1097/MPG.0000000000002279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492264PMC
April 2019

Updates in Pediatric Pancreatology: Proceedings of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Frontiers in Pediatric Pancreatology Symposium.

J Pediatr Gastroenterol Nutr 2019 02;68(2):e27-e33

Division of Pediatric Gastroenterology and Nutrition, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.

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.
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http://dx.doi.org/10.1097/MPG.0000000000002186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444930PMC
February 2019

Blood Urea Nitrogen Elevation Is a Marker for Pediatric Severe Acute Pancreatitis.

Pancreas 2019 03;48(3):363-366

Department of Pediatrics, University of Cincinnati College of Medicine.

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.
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http://dx.doi.org/10.1097/MPA.0000000000001265DOI Listing
March 2019

Prevalence of abnormal glucose metabolism in pediatric acute, acute recurrent and chronic pancreatitis.

PLoS One 2018 31;13(10):e0204979. Epub 2018 Oct 31.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.

Type 3C Diabetes, or diseases of the exocrine pancreas has been reported to occur in approximately 30% of adult patient with pancreatitis. The incidence of glucose abnormalities or risk factors that may predict the development of abnormal glucose in the pediatric pancreatitis population is not known. We performed a retrospective chart review from 1998-2016 for patients who carry the diagnosis of acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP). We extracted glucose values, HbA1c%, and data from oral glucose tolerance and mixed meal testing with timing in relation to pancreatic exacerbations. Patient characteristic data such as age, gender, body proportions, family history of pancreatitis, exocrine function and genetic mutations were also assessed. Abnormal glucose was based on definitions put forth by the American Diabetes Society for pre-diabetes and diabetes. Fifty-two patients had AP and met criteria. Of those, 15 (29%) had glucose testing on or after the first attack, 21 (40%) were tested on or after the second attack (in ARP patients) and 16 (31%) were tested after a diagnosis of CP. Of the patients tested for glucose abnormalities, 25% (13/52) had abnormal glucose testing (testing indicating pre-DM or DM as defined by ADA guidelines. A significantly higher proportion of the abnormal glucose testing was seen in patients (85%, 11/13) with a BMI at or greater than the 85th percentile compared to the normal glucose patients (28%, 11/39) (p = 0.0007). A significantly higher proportion of the abnormal glucose patients (77%, 10/13) had SAP during the prior AP episode to testing compared to the 10% (4/39) of the normal glucose patients (p<0.0001). Older age at DM testing was associated with a higher prevalence of abnormal glucose testing (p = 0.04). In our patient population, a higher proportion of glucose abnormalities were after the second episode of pancreatitis, however 62% (8/13) with abnormalities was their first time tested. We identified obesity and having severe acute pancreatitis (SAP) during the prior AP episode to testing could be associated with abnormal glucose. We propose that systematic screening for abnormal glucose after the first episode of acute pancreatitis in order to better establish the timing of diabetes progression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204979PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209152PMC
March 2019