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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.

Preservation of native esophagus is a tenet of esophageal atresia (EA) repair. However, techniques for delayed primary anastomosis are severely limited for surgically and medically complex patients at high-risk for operative repair. We report our initial experience with the novel application of the Connect-EA, an esophageal magnetic compression anastomosis device, for salvage of primary repair in 2 high-risk complex EA patients. Compassionate use was approved by the FDA and treating institutions.Two approaches using the Connect-EA are described - a totally endoscopic approach and a novel hybrid operative approach. To our knowledge, this is the first successful use of a hybrid operative approach with an esophageal magnetic compression device.Salvage of delayed primary anastomosis was successful in both patients. The totally endoscopic approach significantly reduced operative time and avoided repeat high-risk operation. The hybrid operative approach salvaged delayed primary anastomosis and avoided cervical esophagostomy.The Connect-EA is a novel intervention to achieve delayed primary esophageal repair in complex EA patients with high-risk tissue characteristics and multi-system comorbidities that limit operative repair. We propose a clinical algorithm for use of the totally endoscopic approach and hybrid operative approach for use of the Connect-EA in high-risk complex EA patients.

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.

Objectives In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. Study design A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. Results A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. Conclusions A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.

Objectives The aim of the study was to assess the methodology and content of nutrition education during gastroenterology fellowship training and the variability among the different programs. Methods A survey questionnaire was completed by 43 fellowship training directors of 62 active programs affiliated to the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, including sites in the United States, Canada, and Mexico. The data were examined for patterns in teaching methodology and coverage of specific nutrition topics based on level 1 training in nutrition, which is the minimum requirement according to the published North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition fellowship training guidelines. Results The majority of the teaching was conducted by MD-degree faculty (61%), and most of the education was provided through clinical care experiences. Only 31% of the level 1 nutrition topics were consistently covered by >80% of programs, and coverage did not correlate with the size of the programs. Competency in nutrition training was primarily assessed through questions to individuals or groups of fellows (77% and 65%, respectively). Program directors cited a lack of faculty interested in nutrition and a high workload as common obstacles for teaching. Conclusions The methodology of nutrition education during gastroenterology fellowship training is, for the most part, unstructured and inconsistent among the different programs. The minimum level 1 requirements are not consistently covered. The development of core curriculums and learning modules may be beneficial in improving nutrition education.

Objective To characterize the natural history of intestinal failure (IF) among 14 pediatric centers during the intestinal transplantation era. Study design The Pediatric Intestinal Failure Consortium performed a retrospective analysis of clinical and outcome data for a multicenter cohort of infants with IF. Entry criteria included infants 60 continuous days. Enteral autonomy was defined as discontinuation of PN for >3 consecutive months. Values are presented as median (25th, 75th percentiles) or as number (%). Results 272 infants with a gestational age of 34 weeks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 months (11.2, 40.9). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). Prescribed medications included oral antibiotics (207, 76%), H2 blockers (187, 69%), and proton pump inhibitors (156, 57%). Enteral feeding approaches varied among centers; 19% of the cohort received human milk. The cohort experienced 8.9 new catheter-related blood stream infections per 1000 catheter days. The cumulative incidences for enteral autonomy, death, and intestinal transplantation were 47%, 27%, and 26%, respectively. Enteral autonomy continued into the fifth year after study entry. Conclusions Children with IF endure significant mortality and morbidity. Enteral autonomy may require years to achieve. Improved medical, nutritional, and surgical management may reduce time on PN, mortality, and need for transplantation.

Canonical Wnt signaling plays a critical regulatory role in development and in stem cell functions and cellular differentiation (41, 43). Wnts initiate a signaling cascade that leads to the nuclear accumulation of β-catenin, which associates with T-cell factor 4 (TCF4), releasing the TCF4-associated transcriptional corepressors and recruiting coactivators to stimulate TCF4-dependent transcription. The intestinal epithelium has been a rich source of information about this pathway. For example, Tcf4 is required for small intestinal stem cell self-renewal; mice lacking this transcription factor exhaust the capacity for continued replenishment of the epithelium in utero (24). Conversely, hyperactive Wnt signaling is closely associated with colorectal carcinoma, most commonly via inactivation of the APC tumor suppressor, which regulates the levels of β-catenin (41, 43). At the end point of the Wnt signaling cascade, β-catenin opposes the action of transcriptional corepressors for binding to TCFs to regulate genes that affect cell fate decisions. Two members of the myeloid translocation gene (MTG) family of transcriptional corepressors, MTG on chromosome 8 (MTG8; also known as ETO or RUNX1T1) and MTG on chromosome 16 (MTG16; also known as ETO2 or CBFA2T3), are disrupted by chromosomal translocations in acute myeloid leukemia (10, 29), which suggests that these factors are key regulators of cellular proliferation or differentiation. As would be expected of master regulatory factors, these targets of chromosomal translocations in acute leukemia are commonly mutated in other tumor types as well. A genomewide screen to detect mutations of genes in colorectal and breast cancer from human patients identified MTG8 (RUNX1T1) as one of 189 new candidate cancer genes. In addition to RUNX1T1, we noted that mutations were also found in CBFA2T3 (MTG16/ETO2) in 2 of the 11 original colorectal tumor samples. Thus, in 5 of 11 colorectal tumor samples, an MTG family member was mutated (49), suggesting that members of this family of transcriptional corepressors are modifiers of cancer-related phenotypes. In the mouse, gene deletion studies indicated that MTG factors play critical roles in gut development. Mtg8 is required for the development of the small and large intestines; 25% of the mice lacking this gene contained a deletion of the midgut, and 80% of the mice died in utero or as neonates (5). Although Mtg8-null mice displayed a deletion of the midgut, the enterocytes and the secretory lineages were present in the intestines of these mice in normal ratios, but the villi were often blunted and disorganized (5). By contrast, deletion of Myeloid Translocation Gene Related-1 (Mtgr1, also known as CBFA2T2) indicated that it was not required for the overall establishment of the gut architecture, but it was required for maintenance of the secretory lineage in the small intestine (1). The inactivation of Mtgr1 appeared to impair lineage allocation in the small intestine at the level of the secretory progenitor or through alterations in intestinal stem cell functions (1, 32). In addition, loss of Mtgr1 sensitized the colonic epithelium to the effects of dextran sodium sulfate and impaired the regeneration of the colonic crypts, suggesting a role for Mtgr1 in the colonic stem cell (32). The loss of goblet, Paneth, and endocrine cells in Mtgr1-null small intestines may be partially attributed to the inactivation of the transcriptional repressor Gfi1 in the secretory progenitor cells, since Gfi1 recruits MTG family members and is required for maintenance of Paneth and goblet cells (1). However, Gfi1-null mice displayed increased numbers of endocrine cells, whereas Mtgr1-null mice showed a reduction in the numbers of these cells (1, 47). This suggested that at least one other transcription factor that mediates cell fate decisions in the small intestine might recruit MTG family proteins to repress transcription. Here we examined whether the other DNA binding transcription factors that play a role in small intestinal lineage decisions and stem cell functions might recruit Mtgr1. We found that TCF4, but not Hes1 or Math1, associates with Mtgr1 and that Mtgr1 can oppose β-catenin-dependent transcriptional activation. In addition, expression of the Xenopus laevis homologue of Mtgr1 impaired axis formation during the development of frog embryos, which is regulated by Wnt signaling, and epistasis analysis indicated that this effect was downstream of β-catenin. Moreover, the c-Myc oncogene, which is regulated by TCF4 and β-catenin, was activated upon removal of Mtgr-1, which may begin to explain why this gene family is so frequently mutated in human cancer.

Background & Aims: The disruption of homeostasis between proliferation and apoptosis in the colonic epithelium contributes to the pathogenesis of human ulcerative colitis. Mice lacking the transcriptional corepressor myeloid translocation gene related-1 (Mtgr1) display impaired secretory cell lineage development in the small intestine and an increase in proliferation in the crypts of both the small and large intestines. Despite the increase in proliferating cells, the colons of Mtgr1-null mice have a normal cell lineage distribution and normal architecture. To uncover colonic phenotypes in Mtgr1−/− mice, we stressed the colonic epithelium with low-molecular-weight dextran sodium sulfate (DSS), which is a well-studied model of murine ulcerative colitis. Methods: Mtgr1-null mice were given 3% DSS in their drinking water for 4 days and the colons examined at various times thereafter for ulceration and for changes in proliferation and apoptosis. Results: Treatment with DSS resulted in severe colitis in Mtgr1−/− mice, at least partially due to increased epithelial apoptosis rates. Transplantation of wild-type and Mtgr1-null bone marrow into irradiated wild-type mice demonstrated that the severe DSS-induced ulceration seen in Mtgr1-null mice was due to a colonic, rather than a hematologic, defect. Importantly, the epithelium of DSS-treated Mtgr1-null mice failed to completely regenerate, showing changes consistent with chronic colitis, even 10 weeks after a single DSS treatment. Conclusions: These findings suggest that Mtgr1 has an important role in crypt survival and regeneration after colonic epithelial ulceration.

Background. Pediatric intestinal failure (IF) is a rare but devastating condition defined as the inability of the intestine to support growth and development without supplemental parenteral nutrition (PN). A retrospective study was performed to provide the foundation for the first prospective study of IF in North America. Methods. PIFCon includes 14 sites with multi-disciplinary IF management teams; 9 are also intestinal transplant (ITx) centers. Infants 60 continuous days for IF were included. Demographic, clinical, biochemical, nutritional and outcome data were abstracted from medical charts. Values are presented as median (25th, 75th percentiles) or as (n, %). Enteral autonomy (EA) was defined as the discontinuation of PN for > 3 consecutive mo. Results. 272 infants with a gestational age of 34 wks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 mo (11.2, 40.9). The majority were male (156, 57%) and Caucasian (204, 75%). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), intestinal atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), intestinal aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). The cumulative proportions achieving EA at 1 and 3 yr were 0.31 and 0.43, respectively. Commonly used medications were oral antibiotics (207, 76%), H2 blockers (187, 69%), and PPIs (156, 57%). Breast milk was given to 52 (19%); the cumulative probabilities of oral solid feeding were .67 at 1 yr and .85 at 3 yr. 25 different infant formulas were used as initial diet; 40 different formulas were used overall. 3.3 new catheter related blood stream infections occurred per person year (PPY) on PN and 0.2 intestinal bleeding episodes PPY of observation. 28 bowel lengthening procedures were performed. Cumulative probability of survival (CPS) was 0.84 at 1 yr and 0.74 at 3 yr. 58 died before and 10 died after ITx. Following study entry, time to death without ITx was 8.2 mo (4.8, 12.6). 137 were alive without ITx when the last data were abstracted from the medical record. 60 received ITx, the cumulative incidence of ITx at 1 and 3 years was .087 and .229, respectively. The CPS 1 year after ITx was 0.84. Conclusions. Children with IF suffer a high rate of mortality and morbidity. EA may require years to achieve. Substantial practice variability is noted among sites. Improved medical, nutritional, and surgical management of IF may reduce time on PN, mortality and need for ITx. Grant support: NIH/NIDDK R21 DK081059-01