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Background The objective of our study was to describe the workup, management, and outcomes of pediatric patients with breast masses undergoing operative intervention. Materials and methods A retrospective cohort study was conducted of girls 10-21 y of age who underwent surgery for a breast mass across 11 children's hospitals from 2011 to 2016. Demographic and clinical characteristics were summarized. Results Four hundred and fifty-three female patients with a median age of 16 y (IQR: 3) underwent surgery for a breast mass during the study period. The most common preoperative imaging was breast ultrasound (95%); 28% reported the Breast Imaging Reporting and Data System (BI-RADS) classification. Preoperative core biopsy was performed in 12%. All patients underwent lumpectomy, most commonly due to mass size (45%) or growth (29%). The median maximum dimension of a mass on preoperative ultrasound was 2.8 cm (IQR: 1.9). Most operations were performed by pediatric surgeons (65%) and breast surgeons (25%). The most frequent pathology was fibroadenoma (75%); 3% were phyllodes. BI-RADS scoring ≥4 on breast ultrasound had a sensitivity of 0% and a negative predictive value of 93% for identifying phyllodes tumors. Conclusions Most pediatric breast masses are self-identified and benign. BI-RADS classification based on ultrasound was not consistently assigned and had little clinical utility for identifying phyllodes.

Intestinal failure-associated liver disease is a major morbidity associated with short bowel syndrome. We sought to determine if the obesity-resistant mouse strain (129S1/SvImJ) conferred protection from liver injury after small bowel resection (SBR). Using a parenteral nutrition-independent model of resection-associated liver injury, C57BL/6J and 129S1/SvImJ mice underwent a 50% proximal SBR or sham operation. At postoperative week 10, hepatic steatosis, fibrosis, and cholestasis were assessed. Hepatic and systemic inflammatory pathways were evaluated using oxidative markers and abundance of tissue macrophages. Potential mechanisms of endotoxin resistance were also explored. Serum lipid levels were elevated in all mouse lines. Hepatic triglyceride levels were no different between mouse strains, but there was an increased accumulation of free fatty acids in the C57BL/6J mice. Histological and serum markers of hepatic fibrosis, steatosis, and cholestasis were significantly elevated in resected C57BL/6J SBR mice as well as oxidative stress markers and macrophage recruitment in both the liver and visceral white fat in C57BL/6J mice compared with sham controls and the 129S1/SvImJ mouse line. Serum endotoxin levels were significantly elevated in C57BL/6J mice with significant elevation of hepatic TLR4 and reduction in PPARα expression levels. Despite high levels of serum lipids, 129S1/SvImJ mice did not develop liver inflammation, fibrosis, or cholestasis after SBR, unlike C57BL/6J mice. These data suggest that the accumulation of hepatic free fatty acids as well as increased endotoxin-driven inflammatory pathways through PPARα and TLR4 contribute to the liver injury seen in C57BL/6J mice with short bowel syndrome. NEW & NOTEWORTHY Unlike C57BL/6 mice, the 129S1/SvImJ strain is resistant to liver inflammation and injury after small bowel resection. These disparate outcomes are likely due to the accumulation of hepatic free fatty acids as well as increased endotoxin-driven inflammatory pathways through PPARα and TLR4 in C57BL/6 mice with short bowel syndrome.

Short bowel syndrome (SBS) is associated with diminished levels of serum fats caused by unknown mechanisms. We have shown that mesenteric lymphatics remodel to a more primitive state one week after small bowel resection (SBR); therefore, this study focuses on the effect of chronic lymphatic remodeling and magnitude of resection on intestinal fatty acid uptake and transport. C57BL6 and Prox1 creER-Rosa26LSLTdTomato (lymphatic reporter) mice underwent 50% or 75% proximal SBR or sham operations. Functional transport of lipids and fecal fat content was measured and lymphatic vasculature was compared via imaging. There was a significant reduction in functional transport of cholesterol and triglyceride after SBR with increasing loss of bowel, mirrored by a progressive increase in fecal fat content. We also describe significant morphological changes in the lymphatic vasculature in both the lamina propria and mesentery. Intestinal lymphatic drainage assay in vivo demonstrated a marked reduction of systemic absorption after resection. Intestinal lymphatic vessels significantly remodel in the setting of chronic SBS. This remodeling results in impaired intestinal transport of fat via the compromised lymphatic architecture, contributing to decreased fatty acid uptake. We believe that these changes may contribute to the development of IFALD, a major morbidity in patients with SBS.

Background The optimal regimen for enteral nutritional support in the management of children with short bowel syndrome (SBS) is not well characterized. A high fat, enteral diet is theoretically beneficial due to increased caloric density and enhanced structural adaptation. We therefore sought to determine the long-term effects of a high fat diet (HFD) on liver injury, a common complication of SBS, compared to a standard chow (SC) diet. Methods Using a parenteral nutrition-independent model of resection-associated liver injury, C57BL/6 mice underwent a sham operation or a 50% or 75% proximal small bowel resection (SBR). Mice in each group were then fed either a HFD (35% kcal fat) or SC (13% kcal fat). At post-operative week 15, markers of liver injury were quantified. Results Liver triglyceride levels were increased from 7- to 19-fold in mice on the HFD compared to mice fed SC in the sham, 50%, and 75% resection groups. Serum ALT (2.2-fold increase in 75% resected mice compared to sham controls) and AST (2.0- and 2.7-fold increases in 50% and 75% resected mice, respectively) levels as well as fibrotic liver staining were elevated only in resected mice fed a HFD. Conclusion Long-term enteral feeding of HFD in our murine SBS model is associated with hepatic steatosis and liver injury. Our observation that liver steatosis and injury occur independent of parenteral nutrition suggests that enteral feeding composition and magnitude of intestinal loss may make a significant contribution to intestinal failure-associated liver disease.

This study evaluated compliance with a multi-institutional quality improvement management protocol for Type-C esophageal atresia with distal tracheoesophageal fistula (EA/TEF).Compliance and outcomes before and after implementation of a perioperative protocol bundle for infants undergoing Type-C EA/TEF repair were compared across 11 children's hospitals from 1/2016-1/2019. Bundle components included elimination of prosthetic material between tracheal and esophageal suture lines during repair, not leaving a transanastomotic tube at the conclusion of repair (NO-TUBE), obtaining an esophagram by postoperative-day-5, and discontinuing prophylactic antibiotics 24 h postoperatively.One-hundred seventy patients were included, 40% pre-protocol and 60% post-protocol. Bundle compliance increased 2.5-fold pre- to post-protocol from 17.6% to 44.1% (p 0.001). After stratifying by institutional compliance with all bundle components, 43.5% of patients were treated at low-compliance centers (20%), 43% at medium-compliance centers (20-80%), and 13.5% at high-compliance centers (80%). Rates of esophageal leak, anastomotic stricture, and time to full feeds did not differ between pre- and post-protocol cohorts, though there was an inverse correlation between NO-TUBE compliance and stricture rate over time (ρ = -0.75, p = 0.029).Compliance with our multi-institutional management protocol increased 2.5-fold over the study period without compromising safety or time to feeds and does not support the use of transanastomotic tubes.Level II.Treatment Study.

After 50% proximal small bowel resection (SBR) in mice, we have demonstrated hepatic steatosis, impaired glucose metabolism without insulin resistance, and increased pancreatic islet area. We sought to determine the consequences of SBR on pancreatic β-cell morphology, proliferation, and expression of a key regulatory hormone, glucagon-like peptide-1 (GLP-1). C57BL/6 mice underwent 50% SBR or sham operation. At 10 wk, pancreatic insulin content and secretion was measured by ELISA. Immunohistochemistry was performed to determine structural alterations in pancreatic α-and β-cells. Western blot analysis was used to measure GLP-1R expression, and immunoassay was used to measure plasma insulin and GLP-1. Experiments were repeated by administering a GLP-1 agonist (exendin-4) to a cohort of mice following SBR. After SBR, there was pancreatic islet hypertrophy and impaired glucose tolerance. The proportion of α and β cells was not grossly altered. Whole pancreas and pancreatic islet insulin content was not significantly different; however, SBR mice demonstrated decreased insulin secretion in both static incubation and islet perfusion experiments. The expression of pancreatic GLP-1R was decreased approximately twofold after SBR, compared with sham and serum GLP-1, was decreased. These metabolic derangements were mitigated after administration of the GLP-1 agonist. Following massive SBR, there is significant hypertrophy of pancreatic islet cells with morphologically intact α- and β-cells. Significantly reduced pancreatic insulin release in both static and dynamic conditions demonstrate a perturbed second phase of insulin secretion. GLP-1 is a key mediator of this amplification pathway. Decreased expression of serum GLP-1 and pancreatic GLP-1R in face of no change in insulin content presents a novel pathway for enteropancreatic glucose regulation following SBR. NEW & NOTEWORTHY Metabolic changes occur following intestinal resection; however, the effects on pancreatic function are unknown. Prior studies have demonstrated that glucagon-like protein-1 (GLP-1) signaling is a crucial player in the improved insulin sensitivity after bariatric surgery. In this study, we explore the effect of massive small bowel resection on gut hormone physiology and provide novel insights into the enteropancreatic axis.

Background Short bowel syndrome occurs following massive small bowel resection (SBR) and is one of the most lethal diseases of childhood. We have previously demonstrated hepatic steatosis, altered gut microbiome, and increased fat deposition in our murine model of SBR. These novel findings prompted us to investigate potential alterations in glucose metabolism and systemic inflammation following intestinal resection. Methods Male C57BL6 mice underwent 50% proximal SBR or sham operation. Body weight and composition were measured. Fasting blood glucose (FBG), glucose, and insulin tolerance testing were performed. Small bowel, pancreas, and serum were collected at sacrifice and analyzed. Results SBR mice gained less weight than shams after 10weeks. Despite this, FBG in resected mice was significantly higher than sham animals. After SBR, mice demonstrated perturbed body composition, higher blood glucose, increased pancreatic islet area, and increased systemic inflammation compared with sham mice. Despite these changes, we found no alteration in insulin tolerance after resection. Conclusions After massive SBR, we present evidence for abnormal body composition, glucose metabolism, and systemic inflammation. These findings, coupled with resection-associated hepatic steatosis, suggest that massive SBR (independent of parenteral nutrition) results in metabolic consequences not previously described and provides further evidence to support the presence of a novel resection-associated metabolic syndrome.

This review aims to discuss the role of nutrition and feeding practices in necrotizing enterocolitis (NEC), NEC prevention, and its complications, including surgical treatment. A thorough PubMed search was performed with a focus on meta-analyses and randomized controlled trials when available. There are several variables in nutrition and the feeding of preterm infants with the intention of preventing necrotizing enterocolitis (NEC). Starting feeds later rather than earlier, advancing feeds slowly and continuous feeds have not been shown to prevent NEC and breast milk remains the only effective prevention strategy. The lack of medical treatment options for NEC often leads to disease progression requiring surgical resection. Following resection, intestinal adaptation occurs, during which villi lengthen and crypts deepen to increase the functional capacity of remaining bowel. The effect of macronutrients on intestinal adaptation has been extensively studied in animal models. Clinically, the length and portion of intestine that is resected may lead to patients requiring parenteral nutrition, which is also reviewed here. There remain significant gaps in knowledge surrounding many of the nutritional aspects of NEC and more research is needed to determine optimal feeding approaches to prevent NEC, particularly in infants younger than 28 weeks and

Background Short gut syndrome (SGS) following massive small bowel resection (SBR) is a major cause of pediatric mortality and morbidity secondary to nutritional deficiencies and the sequelae of chronic total parenteral nutrition use, including liver steatosis. Despite the importance of lymphatic vasculature in fat absorption, lymphatic response after SBR has not been studied. We hypothesize that lymphatic vessel integrity is compromised in SGS, potentially contributing to the development of impaired lipid transport leading to liver steatosis and metabolic disease. Methods Mice underwent 50% proximal SBR or sham operations. Imaging of lymphatic vasculature in the lamina propria and mesentery was compared between sham and SBR Prox1 ERCre-Rosa26LSLTdTomato mice. mRNA expression levels of lymphangiogenic markers were performed in C57BL/6J mice. Results Lymphatic vasculature was significantly altered after SBR. Mesenteric lymphatic collecting vessels developed new branching structures and lacked normal valves at branch points, while total mucosal lymphatic capillary area in the distal ileum decreased compared to both sham and intraoperative controls. Intestinal Vegfr3 expression also increased significantly in resected mice. Conclusions Intestinal lymphatics, in both the lamina propria and mesentery, dramatically remodel following SBR. This remodeling may affect lymphatic flow and function, potentially contributing to morbidities and nutritional deficiencies associated with SGS.

The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients.Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively. Research for prevention and treatment is aimed at alleviating risk factors associated with IFALD, principally those associated with parental nutrition. Multiple nutrients and amino acids are relevant to the development of IFALD, but lipid composition has been the primary focus. Lipid emulsions with a lower ratio of omega-6-to-omega-3 polyunsaturated fatty acids (FAs) appear to improve bile flow and decrease intrahepatic inflammation. Long-term consequences of these alternative lipid emulsions are yet to be determined.IFALD remains the greatest contributor of mortality in patients with intestinal failure. Many factors contribute to its development, namely, alterations in the gut microbiome, sepsis, and lack of enteral intake. Novel combinations of lipid formulations are promising alternatives to purely soy-based formulas to reduce cholestasis.