Publications by authors named "Maisam Abu-El-Haija"

103 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

Menstruation-Associated Acute Pancreatitis in Patients with Hereditary Pancreatitis.

J Pediatr 2021 Mar 22;230:248-250. Epub 2020 Nov 22.

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

Two adolescent girls presented with recurrent episodes of menstrual cycle-associated acute pancreatitis and are diagnosed with hereditary pancreatitis, a cause of chronic pancreatitis. Hereditary pancreatitis should remain in the differential diagnosis for teenage girls with catamenial acute pancreatitis and family history of pancreatic disease.
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http://dx.doi.org/10.1016/j.jpeds.2020.11.024DOI Listing
March 2021

Medical Management of Chronic Pancreatitis in Children: A Position Paper by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee.

J Pediatr Gastroenterol Nutr 2021 Feb;72(2):324-340

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

Abstract: This position paper summarizes the current understanding of the medical management of chronic pancreatitis (CP) in children in light of the existing medical literature, incorporating recent advances in understanding of nutrition, pain, lifestyle considerations, and sequelae of CP. This article complements and is intended to integrate with parallel position papers on endoscopic and surgical aspects of CP in children. Concepts and controversies related to pancreatic enzyme replacement therapy (PERT), the use of antioxidants and other CP medical therapies are also reviewed. Highlights include inclusion of tools for medical decision-making for PERT, CP-related diabetes, and multimodal pain management (including an analgesia ladder). Gaps in our understanding of CP in children and avenues for further investigations are also reviewed.
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http://dx.doi.org/10.1097/MPG.0000000000003001DOI Listing
February 2021

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

Noninvasive imaging of pediatric pancreatitis: joint recommendations from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the Society for Pediatric Radiology.

Pediatr Radiol 2021 Jan 15;51(1):8-10. Epub 2020 Oct 15.

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

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http://dx.doi.org/10.1007/s00247-020-04813-yDOI Listing
January 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

North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the Society for Pediatric Radiology Joint Position Paper on Noninvasive Imaging of Pediatric Pancreatitis: Literature Summary and Recommendations.

J Pediatr Gastroenterol Nutr 2021 Jan;72(1):151-167

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.

Abstract: The reported incidence of pediatric pancreatitis is increasing. Noninvasive imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), play important roles in the diagnosis, staging, follow-up, and management of pancreatitis in children. In this position paper, generated by members of the Pancreas Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the Abdominal Imaging Committee of The Society for Pediatric Radiology (SPR), we review the roles of noninvasive imaging in pediatric acute, acute recurrent, and chronic pancreatitis. We discuss available evidence related to noninvasive imaging, highlighting evidence specific to pediatric populations, and we make joint recommendations for use of noninvasive imaging. Further, we highlight the need for research to define the performance and role of noninvasive imaging in pediatric pancreatitis.
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http://dx.doi.org/10.1097/MPG.0000000000002964DOI Listing
January 2021

Endoscopic Pancreatic Function Testing (ePFT) in Children: A Position Paper From the NASPGHAN Pancreas Committee.

J Pediatr Gastroenterol Nutr 2021 Jan;72(1):144-150

Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, Palo Alto, CA.

Abstract: Endoscopic pancreatic function testing (ePFT) is one of the few ways to directly diagnose exocrine pancreatic insufficiency, and considerable confusion regarding indications, utility, and interpretation of the test remains. This position paper of the Pancreas Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition reviews the history and indications for ePFT in children. We compare various methods in current practice and determine their strengths and limitations, and based on data from children and adults we provide guidance on a protocol on how to perform ePFT in children. Lastly, we pose areas in need of further research relating to ePFT in children.
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http://dx.doi.org/10.1097/MPG.0000000000002931DOI Listing
January 2021

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

Validation of threshold values for pancreas thickness and T1-weighted signal intensity ratio in the pediatric pancreas.

Pediatr Radiol 2020 09 16;50(10):1381-1386. Epub 2020 Jun 16.

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

Background: Pancreas atrophy and the loss of T1-weighted signal intensity by magnetic resonance imaging (MRI) are findings of chronic pancreatitis.

Objective: The purpose of this study was to test published normal values and cutoffs for pancreas thickness and the pancreas:spleen T1-weighted signal intensity ratio in children without pancreatic disease.

Materials And Methods: This was a secondary analysis of prospectively collected MRI data for 50 children (range: 6.3-15.9 years; 27 female) with no history of pancreatic disease. Two observers (R1, R2) measured linear pancreas thickness on axial T1-weighted, fat-saturated gradient recalled echo images and placed regions of interest in the pancreas and spleen to calculate the T1-weighted signal intensity ratio. Measurements were compared to published pediatric normal values (computed tomography [CT], ultrasound [US]) and adult cutoffs (CT, MRI).

Results: Compared to published pediatric values for CT, 68% (R1: 34/50) or 40% (R2: 22/50) of participants had ≥1 pancreas segment with thickness below the normal range. No participant had a thickness value below the normal range published for US. Compared to cutoff values in adults, 84% (R1: 42/50) or 80% (R2: 40/50) of participants met the criteria for pancreas atrophy. Mean T1-weighted signal intensity ratio was 1.33±0.15 (R1) and 1.32±0.16 (R2). Twelve (R1: 24.5% of 49) or 11/49 (R2: 22.4%) participants had a T1-weighted signal intensity ratio below the threshold associated with exocrine insufficiency in adults.

Conclusion: Previously defined thresholds for pancreas thickness and pancreas:spleen T1-weighted signal intensity ratio appear too restrictive for a pediatric population. Further study is needed to define optimal quantitative metrics for findings of chronic pancreatitis in children.
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http://dx.doi.org/10.1007/s00247-020-04733-xDOI Listing
September 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

Patient Passport for Pediatric Acute Recurrent and Chronic Pancreatitis.

J Pediatr Gastroenterol Nutr 2020 07;71(1):e51-e53

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, Palo Alto.

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http://dx.doi.org/10.1097/MPG.0000000000002754DOI Listing
July 2020

The Roles of Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography in the Evaluation and Treatment of Chronic Pancreatitis in Children: A Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee.

J Pediatr Gastroenterol Nutr 2020 05;70(5):681-693

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

Introduction: Pediatric chronic pancreatitis is increasingly diagnosed. Endoscopic methods [endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography (ERCP)] are useful tools to diagnose and manage chronic pancreatitis. Pediatric knowledge and use of these modalities is limited and warrants dissemination.

Methods: Literature review of publications relating to use of ERCP and EUS for diagnosis and/or management of chronic pancreatitis with special attention to studies involving 0--18 years old subjects was conducted with summaries generated. Recommendations were developed and voted upon by authors.

Results: Both EUS and ERCP can be used even in small children to assist in diagnosis of chronic pancreatitis in cases where cross-sectional imaging is not sufficient to diagnose or characterize the disease. Children under 15 kg for EUS and 10 kg for ERCP can be technically challenging. These procedures should be done optimally by appropriately trained endoscopists and adult gastroenterology providers with appropriate experience treating children. EUS and ERCP-related risks both include perforation, bleeding and pancreatitis. EUS is the preferred diagnostic modality over ERCP because of lower complication rates overall. Both modalities can be used for management of chronic pancreatitis -related fluid collections. ERCP has successfully been used to manage pancreatic duct stones.

Conclusion: EUS and ERCP can be safely used to diagnose chronic pancreatitis in pediatric patients and assist in management of chronic pancreatitis-related complications. Procedure-related risks are similar to those seen in adults, with EUS having a safer risk profile overall. The recent increase in pediatric-trained specialists will improve access of these modalities for children.
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http://dx.doi.org/10.1097/MPG.0000000000002664DOI Listing
May 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

Hypertriglyceridemia Induced Pancreatitis: Inpatient Management at a Single Pediatric Institution.

Pancreas 2020 03;49(3):429-434

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

Objectives: Hypertriglyceridemia-induced pancreatitis is an important cause of acute pancreatitis (AP) in children, which lacks established guidelines. The aim of this study was to review management approaches at a single pediatric center.

Methods: This retrospective study included all inpatients younger than 21 years with AP and triglycerides (TG) of 1000 mg/dL or greater. A linear mixed effect model was used to calculate drop in TGs. The patient's diet, intravenous fluid (IVF) rate, insulin, and plasmapheresis were included in the model.

Results: Seventeen admissions were identified among 8 patients, average age 15 years (range, 6-19 years). Fifty percent had recurrent AP and 29% of admissions had complications including 1 death. The population was primarily female (75%), white (75%), and overweight, and 63% had diabetes. The median stay was 5.4 days. There were 14 approaches used with variations in IVF rates, insulin, plasmapheresis, and nill per os (NPO) versus feeds. Variables that reduced TG's were NPO, higher IVF rates, plasmapheresis, and insulin (P < 0.05). Importantly, NPO reduced TGs faster than those who started early nutrition.

Conclusions: Hypertriglyceridemia is an important cause of pancreatitis in children. This study shares a management algorithm from a single institution. Larger studies are needed for more evidence-based guidelines.
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http://dx.doi.org/10.1097/MPA.0000000000001505DOI Listing
March 2020

Use of Lactated Ringers Solution Compared With Normal Saline Is Associated With Shorter Length of Stay in Pediatric Acute Pancreatitis.

Pancreas 2020 03;49(3):375-380

Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Objective: The aim of the study was to evaluate lactated ringers (LR) versus normal saline (NS) in pediatric acute pancreatitis (AP).

Methods: This retrospective study used Pediatric Health Information System database of primary AP patients, 2013 to 2017.

Results: The study included 1581 first time AP patients with exclusive use of a single fluid (111 LR, 1470 NS) for the first 48 hours. The LR cohort had a significantly shorter length of stay (P < 0.001) compared with NS. A multivariable logistic regression analysis suggests use of NS in the first 48 hours (after controlling for total parenteral nutrition, operation, and infection during the admission) had a significantly increased likelihood of requiring a hospitalization for 4 days or more compared with the LR group (odds ratio, 3.31; 95% confidence interval, 1.95-5.62). The overall cost was significantly less in the LR group. There was no statistical difference observed in risk factors for AP, intensive care transfer, organ dysfunction, or mortality.

Conclusions: This represents the first large data set analysis of LR versus NS in pediatric AP. The use of LR was associated with a shorter length of stay and reduced cost compared with NS. Future randomized trials will help determine the ideal fluid choice for pediatric AP.
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http://dx.doi.org/10.1097/MPA.0000000000001498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100996PMC
March 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

Healthy pancreatic parenchymal volume and its relationship to exocrine function.

Pediatr Radiol 2020 05 11;50(5):684-688. Epub 2020 Feb 11.

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

Background: Pancreatic atrophy as a finding of chronic pancreatitis has largely been a subjective finding. Cross-sectional imaging should provide a means to quantify pancreatic atrophy.

Objective: The purposes of this study were to: (1) quantify pancreatic volume by magnetic resonance imaging (MRI) in a cohort of children without pancreatic disease, (2) define predictors of pancreatic volume and (3) assess the relationship between pancreatic volume and pancreatic fluid secretion.

Materials And Methods: This study involved further analysis of data collected as part of an institutional review board-approved prospective study of secreted fluid volume in response to secretin in 50 healthy children ages 6-16 years. The pancreas was manually segmented on axial MR images to calculate pancreatic volume. Pearson correlation or the Student's t-test were used to define associations between pancreatic volume and patient characteristics and previously calculated secreted fluid volume. Quantile regression was used to define the 5th percentile for pancreatic volume based on body surface area (BSA) [1].

Results: Mean pancreatic volume was 46.0±18.8 mL with no significant difference based on sex (boys: 42.4±19 mL, girls: 49.1±18.3 mL, P=0.21). Pancreatic volume was moderately correlated with age (r=0.51, P=0.002) and strongly correlated with BSA (r=0.75, P<0.0001), with the 5th percentile for pancreatic volume defined by: (24.66×BSA) - 4.97. Pancreatic volume was moderately correlated with volume of fluid secreted after secretin administration (r=0.51, P=0.0002).

Conclusion: We report increasing pancreatic volumes by MRI during childhood in a cohort of children without pancreatic disease. We have also shown that pancreatic volume is associated with secreted fluid volume as measured by MRI.
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http://dx.doi.org/10.1007/s00247-019-04605-zDOI Listing
May 2020

Secretin Improves Visualization of Nondilated Pancreatic Ducts in Children Undergoing MRCP.

AJR Am J Roentgenol 2020 04 5;214(4):917-922. Epub 2020 Feb 5.

Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229.

The objective of our study was to assess whether secretin improves visualization of a nondilated pancreatic duct and whether it increases identification of variant duct anatomy on MRCP in pediatric patients. This study is a delayed retrospective review of MRCP images that were prospectively obtained of 50 volunteers without a history of pancreatic disease who ranged in age from 6 to 15 years old. MRCP images (coronal 3D fast recovery fast spin-echo [FSE] and coronal single-shot FSE fat-saturated sequences) obtained before and after secretin administration were separated for review by three radiologists (reviewers 1-3). The reviewers were blinded to the purpose of the study and to secretin administration. Reviewers ranked subjective image quality (Likert scale, 1-5 points) and reported pancreaticobiliary duct anatomy and duct visibility (yes or no). Paired tests were used for comparison of means, and the chi-square test or Fisher exact test was used for comparison of frequencies. Sensitivity and specificity of MRCP images obtained before secretin administration were judged against MRCP images obtained after secretin administration as the reference standard. The frequency of image quality scores of 4 or greater assigned to 3D MRCP images was statistically significantly greater after secretin administration for reviewer 2 ( < 0.0001) and reviewer 3 ( = 0.005) and approached statistical significance for reviewer 1 ( = 0.052). Mean number of visible pancreatic duct segments (head and uncinate, body, tail) was significantly greater on the MRCP images obtained after secretin administration than on those obtained before secretin administration for all reviewers (reviewer 1, 1.9 vs 1.3; reviewer 2, 1.9 vs 1.2; reviewer 3, 1.4 vs 0.8; all, < 0.01). For all three reviewers, the sensitivity of MRCP images obtained before secretin administration was poor for variant pancreatic ductal anatomy (reviewer 1, 37.5%; reviewer 2, 50.0%; reviewer 3, 40.0%). Secretin administration improved subjective MRCP image quality, improved subjective visualization of the pancreatic duct, and provided greater sensitivity for anatomic variants such as pancreas divisum in a cohort of children with nondilated pancreatic ducts.
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http://dx.doi.org/10.2214/AJR.19.21798DOI Listing
April 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