Magnetic resonance imaging T1 mapping of the liver, pancreas and spleen in children.

PURPOSE: To characterize T1 relaxation times of the pancreas, liver, and spleen in children with and without abdominal pathology. METHODS: This retrospective study included pediatric patients (< 18-years-old). T1 mapping was performed with a Modified Look-Locker Inversion Recovery sequence. Patients were grouped based on review of imaging reports and electronic medical records. The Kruskal-Wallis test with Dunn's multiple comparison was used to compare groups. RESULTS: 220 participants were included (mean age: 11.4 ± 4.2 years (1.5 T); 10.9 ± 4.5 years (3 T)). Pancreas T1 (msec) was significantly different between subgroups at 1.5 T (p < 0.0001). Significant pairwise differences included: normal (median: 583; IQR: 561-654) vs. acute pancreatitis (731; 632-945; p = 0.0024), normal vs. chronic pancreatitis (700; 643-863; p = 0.0013), and normal vs. acute + chronic pancreatitis (1020; 897-1099; p < 0.0001). Pancreas T1 was also significantly different between subgroups at 3 T (p < 0.0001). Significant pairwise differences included: normal (779; 753-851) vs. acute pancreatitis (1087; 910-1259; p = 0.0012), and normal vs. acute + chronic pancreatitis (1226; 1025-1367; p < 0.0001). Liver T1 was significantly different between subgroups only at 3 T (p = 0.0011) with pairwise differences between normal (818, 788-819) vs. steatotic (959; 848-997; p = 0.0017) and normal vs. other liver disease (882; 831-904; p = 0.0455). Liver T1 was weakly correlated with liver fat fraction at 1.5 T (r = 0.39; 0.24-0.52; p < 0.0001) and moderately correlated at 3 T (r = 0.64; 0.49-0.76; p < 0.0001). There were no significant differences in splenic T1 relaxation times between subgroups. CONCLUSION: Pancreas T1 relaxation times are higher at 1.5 T and 3 T in children with pancreatitis and liver T1 relaxation times are higher in children with steatotic and non-steatotic chronic liver disease at 3 T.

The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children.

BACKGROUND AND AIMS: Acute pancreatitis (AP) is increasingly recognized as a risk factor for diabetes mellitus (DM). We aimed to study the association of pancreatitis genes with pancreatic endocrine insufficiency (pre-DM and DM) development post AP in children. METHODS: This was an observational cohort study that enrolled subjects ≤21 years with their first episode of AP and followed them for 12 months for the development of pancreatic endocrine insufficiency. Pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable p<0.15 RESULTS: A total 120 subjects with AP were genotyped. Sixty-three subjects (52.5%) had at least 1 reportable variant identified. For modeling the development of pancreatic endocrine insufficiency at one year, 6 were excluded (2 with DM at baseline, 3 with total pancreatectomy, and 1 death).. From this group of 114, 95 remained normoglycemic and 19 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM). Severe AP (58% vs 20%; p=0.001) and at least one gene affected (79% vs 47%, p=0.01) were enriched among the endocrine insufficient group. Those with versus without endocrine insufficiency were similar in age, sex, race, ethnicity, body mass index, and AP recurrence. A model for pre-DM/DM development included AP severity (OR=5.17 [1.66, 16.15], p=0.005) and genetic risk score (OR=4.89 [1.83, 13.08], p=0.002) and had an AUC of 0.74. CONCLUSIONS: In this cohort of children with AP, pancreatitis risk genes and AP disease severity were associated with pre-DM or DM development post AP.

Semi-automated software improves interrater reliability and reduces processing time of magnetic resonance imaging-based exocrine pancreatic assessments in pediatric patients.

OBJECTIVES: Magnetic resonance (MR) imaging with secretin stimulation (MR-PFTs) is a non-invasive test for pancreatic exocrine function based on assessing the volume of secreted bowel fluid in vivo. Adoption of this methodology in clinical care and research is largely limited to qualitative assessment of secretion as current methods for secretory response quantification require manual thresholding and segmentation of MR images, which can be time-consuming and prone to interrater variability. We describe novel software (PFTquant) that preprocesses and thresholds MR images, performs heuristic detection of non-bowel fluid objects, and provides the user with intuitive semi-automated tools to segment and quantify bowel fluid in a fast and robust manner. We evaluate the performance of this software on a retrospective set of clinical MRIs. METHODS: Twenty MRIs performed in children (< 18 years) were processed independently by two observers using a manual technique and using PFTquant. Interrater agreement in measured secreted fluid volume was compared using intraclass correlation coefficients, Bland-Altman difference analysis, and Dice similarity coefficients. RESULTS: Interrater reliability of measured bowel fluid secretion using PFTquant was 0.90 (0.76-0.96 95% C.I.) with - 4.5 mL mean difference (-39.4-30.4 mL 95% limits of agreement) compared to 0.69 (0.36-0.86 95% C.I.) with - 0.9 mL mean difference (-77.3-75.5 mL 95% limits of agreement) for manual processing. Dice similarity coefficients were better using PFTquant (0.88 +/- 0.06) compared to manual processing (0.85 +/- 0.10) but not significantly (p = 0.11). Time to process was significantly (p < 0.001) faster using PFTquant (412 +/- 177 s) compared to manual processing (645 +/- 305 s). CONCLUSION: Novel software provides fast, reliable quantification of secreted fluid volume in children undergoing MR-PFTs. Use of the novel software could facilitate wider adoption of quantitative MR-PFTs in clinical care and research.

Acute pancreatitis is associated with gut dysbiosis in children.

BACKGROUND: Pediatric acute pancreatitis (AP) is associated with significant morbidity. Therefore, improved understanding of children who will develop severe AP is critical. Adult studies have reported AP associated gut dysbiosis, but pediatric studies are lacking. AIMS: Assess stool microbial taxonomic and functional profiles of children with first attack of AP compared to those of healthy controls (HC), and between mild and severe AP METHODS: Children under 21 years hospitalized at a tertiary center (n = 30) with first AP attack were recruited including HC (n = 34) from same region. Shotgun metagenomic sequencing was performed on extracted DNA. RESULTS: Demographics were similar between AP and HC. Alpha diversity (-0.68 ± 0.13, p-value < 0.001), and beta-diversity (R2=0.13, p-value < 0.001) differed, in children with AP compared to HC. Species including R.gnavus, V.parvula, E.faecalis, C.innocuum were enriched in AP. MetaCyc pathways involved in amino acid metabolism and fatty acid beta-oxidation were enriched in AP. Beta-diversity (R2=0.06, p-value = 0.02) differed for severe AP compared to mild AP with enrichment in E.faecalis and C.citroniae. CONCLUSIONS: Gut dysbiosis occurs in pediatric AP and is associated with AP severity. A multicenter study confirming these findings could pave way for interventional trials manipulating the gut microbiome to mitigate AP severity.

Pancreas volumes in pediatric patients following index acute pancreatitis and acute recurrent pancreatitis.

BACKGROUND/OBJECTIVES: Pancreas volume derived from imaging may objectively reveal volume loss relevant to identifying sequelae of acute pancreatitis (AP) and ultimately diagnosing chronic pancreatitis (CP). The purposes of this study were to: (1) quantify pancreas volume by imaging in children with either (a) a single episode of AP or (b) acute recurrent pancreatitis (ARP), and (2) compare these volumes to normative volumes. METHODS: This retrospective study was institutional review board approved. A single observer segmented the pancreas (3D Slicer; slicer.org) on n = 30 CT and MRI exams for 23 children selected from a prospective registry of patients with either an index attack of AP or with ARP after a known index attack date. Patients with CP were excluded. Segmented pancreas volumes were compared to published normal values. RESULTS: Mean pancreas volumes normalized to body surface area (BSA) in the index AP and ARP groups were 38.2 mL/m2 (range: 11.8-73.5 mL/m2) and 27.9 mL/m2 (range: 8.0-69.2 mL/m2) respectively. 43 % (6/14) of patients post-AP had volumes below the 25th percentile, 1 (17 %) of which was below the 5th percentile (p = 0.3027 vs. a normal distribution). Post-ARP, 44 % (7/16) of patients had volumes below the 5th percentile (p < 0.001). CONCLUSIONS: A significant fraction (40 %) of children with ARP have pancreas volumes <5th percentile for BSA even in the absence of CP. A similar, but not statistically significant, fraction have pancreas volumes <25th percentile after an index attack of AP. Pancreatic parenchymal volume deserves additional investigation as an objective marker of parenchymal damage from acute pancreatitis and of progressive pancreatitis in children.

Endocrine Management and Clinical Outcomes in a Cohort of Pediatric Patients Undergoing Total Pancreatectomy with Islet Autotransplantation.

Objective: To describe management strategies that contributed to optimal outcomes in pediatric recipients of a total pancreatectomy with islet autotransplantation (TPIAT). Research Design and Methods: We provide a comprehensive report of the approach to endocrine management of the pediatric TPIAT recipient from initial evaluation through the first 4 years postsurgery. We performed a retrospective review of the endocrine outcomes of TPIAT recipients to describe the impact of this approach on post-TPIAT glycemic management. Results: Outcome data from 86 TPIAT recipients were reviewed. At 12 months post-TPIAT (n = 82), the median HbA1C was 6.0% (25-75th percentile 5.6-6.7), at 18 months (n = 56) HbA1C was 6.4% (5.6-7.5), at 2 years (n = 46) HbA1C was 6.4% (5.6-7.4), at 3 years (n = 31) HbA1C was 6.5% (5.5-8.1), and at 4 years (n = 16) HbA1C was 7.2% (6.2-8.3). Conclusions: Pediatric patients at our institution have favorable endocrine outcomes as evidenced by median HbA1C under the goal of 6.5% through the initial 3 years by following our modified management protocols.

Total pancreatectomy with islet autotransplantation reduces opioid use and improves nutritional support in children with debilitating pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) can result in opioid dependence and nutritional challenges in children. Total pancreatectomy with islet autotransplantation (TPIAT) is a viable surgical option in appropriately selected patients. We examined differences between children who met criteria for TPIAT versus those who did not and continued with non-operative management. METHODS: Retrospective observational cohort study of patients evaluated for TPIAT between August 2014 and July 2020 was performed. Cohort-based analyses between TPIAT and non-TPIAT groups were performed. RESULTS: Analyses included 121 patients, 69 of whom underwent TPIAT. Demographics, genetic risk factors, and anatomic variants did not differ between groups. TPIAT patients were more likely to have CP (88% vs 71%; p = 0.02), had higher median number of endoscopic retrograde cholangiopancreatography procedures (2.0 vs 1.0; p = 0.0001), and had higher likelihood of opioid use (61% vs 42%; p = 0.04) and nutritional supplementation (23% vs 4%; p = 0.004), compared to non-TPIAT. At 6 months post-TPIAT, patients had lower use of any analgesic pain medications (39% vs 73%; p = 0.0002) and lower use of opioids (9% vs 39%; p = 0.0006), compared to non-TPIAT patients at 6 months after evaluation. At 6 months post-TPIAT, rate of exclusively oral nutrition increased from 77% to 86%, and total parenteral nutrition use decreased from 13% to 0% (p = 0.02). CONCLUSIONS: In children referred for TPIAT evaluation, there is greater burden of disease in those selected for operation, compared to patients who do not undergo operation. TPIAT achieves lower analgesic pain medication use compared to continuation with non-TPIAT management and achieves freedom from nutritional supplementation. Level of evidence: Retrospective comparative study, Level III.

Image or scope: Magnetic resonance imaging and endoscopic testing for exocrine and endocrine pancreatic insufficiency in children.

OBJECTIVES: We sought to evaluate associations between Magnetic Resonance Imaging (MRI) findings, exocrine pancreatic insufficiency (EPI) and endocrine insufficiency (prediabetes or diabetes) in children. METHODS: This was a retrospective study that included patients<21 years of age who underwent MRI and endoscopic pancreatic function testing (ePFT; reference standard for pancreatic exocrine function) within 3 months. MRI variables included pancreas parenchymal volume, secreted fluid volume in response to secretin, and T1 relaxation time. Data were analyzed for the full sample as well as the subset without acute pancreatitis (AP) at the time of imaging. RESULTS: Of 72 patients, 56% (40/72) were female with median age 11.4 years. A 5 mL decrease in pancreas parenchymal volume was associated with increased odds of exocrine pancreatic dysfunction by both ePFT (OR = 1.16, p = 0.02 full sample; OR = 1.29, p = 0.01 no-AP subset), and fecal elastase (OR = 1.16, p = 0.04 full sample; OR = 1.23, p = 0.02 no-AP subset). Pancreas parenchymal volume had an AUC 0.71 (95% CI: 0.59, 0.83) for predicting exocrine pancreatic dysfunction by ePFT and when combined with sex and presence of AP had an AUC of 0.82 (95% CI: 0.72, 0.92). Regarding endocrine function, decreased pancreas parenchymal volume was associated with increased odds of diabetes (OR = 1.16, p = 0.03), and T1 relaxation time predicted glycemic outcomes with an AUC 0.78 (95% CI: 0.55-1), 91% specificity and 73% sensitivity. CONCLUSIONS: Pancreas parenchymal volume is an MRI marker of exocrine and endocrine pancreatic dysfunction in children. A model including sex, AP, and pancreas volume best predicted exocrine status. T1 relaxation time is also an MRI marker of endocrine insufficiency.

Risk Factors for Post-ERCP Pancreatitis in Pediatric and Young Adult Patients.

OBJECTIVES: Post-ERCP pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Limited existing data suggest that prophylactic pancreatic duct (PD) stenting in pediatric patients may increase the risk of PEP. The aim of this study is to identify factors associated with PEP in pediatric patients. METHODS: Patients at a single institution who underwent ERCP between 2012 and 2020 were retrospectively reviewed. Patient and procedure-related factors were collected. Data were analyzed using Chi-square or Fisher exact tests as appropriate and Mann-Whitney-Wilcoxon tests. RESULTS: Seven hundred thirty-six ERCPs were performed for 402 unique patients. Ninety-four cases were complicated by PEP (12.8%), of which 91 were mild and 3 were moderately severe. Pancreatic indication, native major papilla, PD cannulation and injection, and higher American Society for Gastrointestinal Endoscopy (ASGE) complexity were associated with PEP. A higher proportion of patients who received rectal indomethacin (65% vs 47%, P = 0.002), or who had placement of a prophylactic (31% vs 20%, P = 0.01) or therapeutic PD stent (37% vs 27%, P = 0.04) developed PEP; however, in a subgroup analysis of high-risk patients, this association was not persistent. A smaller proportion of PEP patients had PRSS1 mutation compared to non-PEP patients (22% vs 40%, P = 0.04). CONCLUSIONS: This study evaluates factors associated with developing PEP in a large pediatric cohort. A high rate of PEP was observed, likely secondary to higher rates of pancreatic indication and higher ASGE complexity scores compared to previously reported literature. Randomized prospective trials are needed to better define the utility of various interventions.

Prevalence of Gastrointestinal Symptoms and Impact on Quality of Life at 1-Year Follow-Up of Initial Attack of Acute Pancreatitis.

OBJECTIVES: This study aims to describe the prevalence of gastrointestinal (GI) symptoms following the first time occurrence of acute pancreatitis (AP) and to measure the impact of the episode on patient health-related quality of life (HRQOL) from the perspectives of patients and parents. METHODS: Questionnaires regarding GI symptoms 1 year following the initial occurrence of AP were obtained from 74 pediatric patients. Thirty of these patients completed both the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Gastrointestinal Symptoms and Worry Scales. These data were compared to legacy-matched healthy controls. RESULTS: Children with a standalone occurrence of AP experienced a similar rate of GI symptoms compared to those who progressed to acute recurrent pancreatitis (ARP) within 1 year. PedsQL 4.0 Generic Core Scales scores were significantly lower for children self-report and parent proxy-report for patients that experienced AP compared to healthy controls. AP patients also demonstrated significantly more symptoms than healthy controls in the Gastrointestinal Symptoms and Worry Scales across multiple domains. CONCLUSIONS: Gastrointestinal symptoms affect many children who experience a single AP event even without recurrent attacks. The burden of symptoms is not significantly different from those who develop ARP. This is a novel study that evaluates patient-reported outcomes in children following an AP attack and demonstrates there is a significant impact on HRQOL in children and family experiences post AP. More data are needed to study the progression of disease and the extended impact of AP following an initial AP attack in pediatric patients.

Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation.

BACKGROUND: Hepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents. OBJECTIVES: To define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT. METHODS: In this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis. RESULTS: A total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2-25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2-40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96). CONCLUSION: Our study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.

Interventional endoscopy for abdominal transplant patients.

Interventional endoscopy can play a significant role in the care and management of children pre-and post- abdominal solid organ transplantation. Such procedures primarily include endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), and balloon-assisted enteroscopy (BAE), though additional interventions are available using standard endoscopes (gastroscopes, colonoscopes) for therapeutics purposes such as endoscopic hemostasis. The availability of pediatric practitioners with the advanced training to effectively and safely perform these procedures are most often limited to large tertiary care pediatric centers. These centers possess the necessary resources and ancillary staff to provide the comprehensive multi-disciplinary care needed for these complex patients. In this review, we discuss the importance of interventional endoscopy in caring for transplant patients, during their clinical course preceding the potential need for solid organ transplantation and inclusion of a discussion related to endoscopic post-surgical complication management. Given the highly important role of interventional endoscopy in patients with recurrent and chronic pancreatitis, we also include a discussion related to this complex disease process leading up to those patients that may need pancreas surgery including total pancreatectomy with islet autotransplantation (TPIAT).

Ultrasound findings of acute pancreatitis in children.

BACKGROUND: Studies systematically documenting US findings in children with acute pancreatitis are limited. Pancreas duct dilation is described as the most reliable finding of acute pancreatitis but this has not been rigorously examined in children. OBJECTIVE: To systematically document US findings in children with acute pancreatitis and to define interobserver agreement on those findings. MATERIALS AND METHODS: In this cross-sectional study we retrospectively reviewed images for all pediatric patients <18 years of age who had been prospectively enrolled in a registry of patients with index admissions for acute pancreatitis between March 2013 and July 2020. Two blinded observers (R1, R2) reviewed the first transabdominal US examination performed within 2 weeks of the pancreatitis attack for each patient. RESULTS: In 141 children, US was performed at a median of 1 day (interquartile range [IQR]: 0, 1) following acute attack. Thirty-three (23%, R1) and 38 (27%, R2) children had no abnormal findings on US. Peripancreatic edema was the most frequent finding documented by both reviewers (63% R1, 54% R2). The pancreatic duct was visible in only 35% of the children and was dilated in only 12% (R1) and 14% (R2). There was substantial to almost-perfect agreement between reviewers on findings of acute pancreatitis (κ=0.62-1), including duct visibility. CONCLUSION: Peripancreatic edema was the most frequently identified finding in children with acute pancreatitis, present in up to 63%, with almost perfect interobserver agreement. Duct dilation, cited in the literature as a reliable finding of acute pancreatitis, was rarely identified in our sample.

Matrix metalloproteinases and their inhibitors in pediatric severe acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is increasing in incidence in adult and pediatric patients. Identification of patients at high risk for progression to severe acute pancreatitis (SAP) is crucial, as it can lead to increased mortality and health system cost. Matrix metalloproteinases (MMPs) are endopeptidases which degrade extracellular matrix proteins and increase activity of pro-inflammatory cytokines. Tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity. Prior limited studies of MMPs and TIMPs have found some to be associated with development of SAP. The aim of this study was to further investigate the role of MMPs and TIMPs in detecting pediatric patients at risk for developing moderately severe AP or SAP. METHODS: Plasma samples were prospectively collected for patients <21 years of age presenting with AP between November 2015 and October 2019, along with healthy controls. Bead-based multiplex assays were utilized to test levels of 12 MMPs and TIMPs. RESULTS: Samples were collected from 7 subjects who developed SAP, 7 with moderately severe AP, 45 with mild AP and 44 healthy controls. MMP-9 (p = 0.04) and TIMP-1 (p = 0.01) levels were significantly higher in SAP patients. A multivariable logistic regression model using MMP-9 and TIMP-1 predicted SAP (AUROC 0.87, 95% CI 0.76-0.98). CONCLUSION: We have demonstrated that MMP9 and TIMP1 levels are increased at AP presentation in pediatric patients who developed SAP during the course of illness. Further studies are needed to validate the use of MMPs and TIMPs as predictive tools for development of SAP in pediatric pancreatitis.

Magnetic Resonance Cholangiopancreatography vs Endoscopy Retrograde Cholangiopancreatography for Detection of Anatomic Variants of the Pancreatic Duct in Children.

OBJECTIVE: To compare the efficacy of magnetic resonance cholangiopancreatography (MRCP) with endoscopy retrograde cholangiopancreatography (ERCP) in children for the identification of pancreatic duct variants. STUDY DESIGN: We identified children with a pancreatic duct variant by ERCP and separately queried our MRCP database for similar variants. Patients with a paired ERCP-MRCP were reviewed. Three radiologists blinded to the ERCP and MRCP findings were asked to independently review the MRCP studies and define the pancreatic duct anatomy. These blinded reviewers also graded the magnetic resonance imaging examination quality. RESULTS: Seventy-four pairs of ERCP-MRCP examinations were identified. Pancreas divisum was the most frequent ductal variant encountered (73%). There was fair agreement between the radiology reviewers as to the quality of the magnetic resonance imaging studies (Fleiss Kappa agreement). Concordance of the reviewers with that of the ERCP was moderate for the exact diagnosis, moderate for the presence of pancreas divisum, and fair for agreement on the presence of any duct variant. Concordance among reviewers was moderate for the exact diagnosis, moderate for normal vs abnormal, and substantial for the presence of pancreas divisum. CONCLUSIONS: Diagnostic limitations exist when comparing MRCP with the gold reference standard of ERCP, specifically when assessing for pancreatic duct variants in children.

Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVE: Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at 1 year following TPIAT in a cohort of children. RESEARCH DESIGN AND METHODS: This was a review of 43 pediatric patients followed after TPIAT for 1 year or longer. Primary outcome was insulin use at 1 year, categorized as follows: insulin independent, low insulin requirement (<0.5 units/kg/day), or high insulin requirement (≥0.5 units/kg/day). RESULTS: At 1 year after TPIAT, 12 of 41 (29%) patients were insulin independent and 21 of 41 (51%) had low and 8 of 41 (20%) had high insulin requirement. Insulin-independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; P = 0.03). Patients with insulin independence had a higher number of transplanted islet equivalents (IEQ) per kilogram body weight (P = 0.03) and smaller body surface area (P = 0.02), compared with those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (P = 0.03). Higher peak C-peptide measured by stimulated mixed-meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at 1 year (P = 0.006 and 0.03, respectively). CONCLUSIONS: We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ per kilogram body weight transplanted, and smaller body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.