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Massive small bowel resection (SBR) is associated with liver injury and fibrosis. Efforts to elucidate the driving force behind hepatic injury have identified multiple factors, including the generation of toxic bile acid metabolites. Sham, 50% proximal, and 50% distal SBR were carried out in C57BL/6 mice to determine the effect of jejunal (proximal SBR) versus ileocecal resection (distal SBR) on bile acid metabolism and liver injury. Tissues were harvested at 2 and 10-week postoperative timepoints. When compared with 50% proximal SBR, mice that underwent distal SBR exhibited less hepatic oxidative stress as verified by decreased mRNA expression of tumor necrosis factor-α (TNFα , p ≤ 0.0001), nicotinamide adenine dinucleotide phosphate oxidase (NOX , p ≤ 0.0001), and glutathione synthetase (GSS , p ≤ 0.05). Distal SBR mice also exhibited a more hydrophilic bile acid profile with reduced abundance of insoluble bile acids (cholic acid (CA), taurodeoxycholic acid (TCA), and taurolithocholic acid (TLCA)), and increased abundance of soluble bile acids (tauroursodeoxycholic acid (TUDCA)). In contrast with proximal SBR, ileocecal resection alters enterohepatic circulation leading to reduced oxidative stress and promotes physiological bile acid metabolism. These findings challenge the notion that preservation of the ileocecal region is beneficial in patients with short bowel syndrome. Administration of selected bile acids may present potential therapy to mitigate resection-associated liver injury. III—Case-Control Study. • DDistal SBR and TUDCA supplementation decreases oxidative stress and SBR-associated hepatic injury. • Distal SBR and TUDCA supplementation have healthier bile acid profiles compared to proximal SBR. • Enterohepatic circulation has critical involvement in liver injury prevention, but distal SBR and TUDCA supplementation likely differ in the mechanism utilized to confer hepatoprotection. [ABSTRACT FROM AUTHOR]

Resection-associated liver steatosis, injury, and fibrosis is a devastating complication associated with massive small bowel resection (SBR). Peroxisome proliferator-activated receptor-alpha (PPARα) is a key regulator of intestinal lipid transport and metabolism whose expression is selectively increased after SBR. Here we asked if attenuating intestinal PPARα signaling would prevent steatosis and liver injury after SBR. Pparα was deleted selectively in adult mouse intestine using a tamoxifen-inducible Cre-LoxP breeding schema. Mice underwent 50% SBR. At 10 weeks post-operatively, metabolic phenotyping, body composition analysis, in vivo assessment of lipid absorption and intestinal permeability, and assessment of adaptation and liver injury was completed. Pparα intestinal knockout and littermate control mice were phenotypically similar in terms of weight trends and body composition after SBR. All mice demonstrated intestinal adaptation with increased villus height and crypt depth; however, Pparα intestinal knockout mice exhibited decreased villus growth at 10 weeks compared to littermate controls. Liver injury and fibrosis were similar between groups as assessed by serum AST and ALT levels, Sirius Red staining, and hepatic expression of Col1a1 and Acta2. Inducible intestinal deletion of Pparα influences structural adaptation but does not mitigate liver injury after SBR. These findings suggest that enterocyte PPARα signaling in adult mice is dispensable for resection-induced liver injury. The results are critical for understanding the contribution of intestinal lipid metabolic signaling pathways to the pathogenesis of hepatic injury associated with short bowel syndrome. • What is known? Resection-associated liver steatosis, injury, and fibrosis is a devastating complication associated with massive small bowel resection. Peroxisome proliferator-activated receptor-alpha is a key regulator of lipid transport and metabolism whose expression is selectively increased in the intestine after SBR. • What is new? Inducible intestinal deletion of PPARα, a major regulator of intestinal lipid metabolism, influences structural adaptation but does not mitigate liver injury after SBR. These findings suggest that enterocyte PPARα signaling in adult mice is dispensable for liver injury following SBR. [ABSTRACT FROM AUTHOR]

Prior data suggest that infants with gastroschisis are at high risk for hypothermia and infectious complications (ICs). This study evaluated the associations between perioperative hypothermia (PH) and ICs in gastroschisis using a multi-institutional cohort. Retrospective review of infants with gastroschisis who underwent abdominal closure from 2013–2017 was performed at 7 children's hospitals. Any-IC and surgical site infection (SSI) were stratified against the presence or absence of PH, and perioperative characteristics associated with PH and SSI were determined using multivariable logistic regression. Of 256 gastroschisis neonates, 42% developed PH, with 18% classified as mild hypothermia (35.5–35.9°C), 10.5% as moderate (35.0–35.4°C), and 13% severe (<35°C). There were 82 (32%) ICs with 50 (19.5%) being SSIs. No associations between PH and any-IC (p = 0.7) or SSI (p = 0.98) were found. Pulmonary comorbidities (odds ratio (OR)=3.76, 95%CI:1.42–10, p = 0.008) and primary closure (OR=0.21, 95%CI:0.12–0.39, p <0.001) were associated with PH, while silo placement (OR=2.62, 95%CI:1.1–6.3, p = 0.03) and prosthetic patch (OR=3.42, 95%CI:1.4–8.3, p = 0.007) were associated with SSI on multivariable logistic regression. Primary abdominal closure and pulmonary comorbidities are associated with PH in gastroschisis, however PH was not associated with increased risk of ICs. Independent risk factors for SSI include silo placement and prosthetic patch closure. [ABSTRACT FROM AUTHOR]

The purpose of our study was to compare outcomes of infants with spontaneous intestinal perforation (SIP) treated with primary peritoneal drain versus primary laparotomy. We performed a multi-institution retrospective review of infants with diagnosis of SIP from 2012 to 2016. Clinical characteristics and outcomes were compared between infants treated with primary peritoneal drain vs infants treated with laparotomy. We identified 171 patients treated for SIP (drain n = 110 vs. laparotomy n = 61). There were no differences in maternal or prenatal characteristics. There were no clinically significant differences in vital signs, white blood cell or platelet measures, up to 48 h after intervention. Patients who were treated primarily with a drain were more premature (24.9 vs. 27.2 weeks, p < 0.001) and had lower median birth weight (710 g vs. 896 g, p < 0.001). No significant differences were found in complications, time to full feeds, length of stay (LOS) or mortality between the groups. Primary laparotomy group had more procedures (median number 1 vs. 2, p = 0.002). There were 32 (29%) primary drain failures whereby a laparotomy was ultimately needed. SIP treated with primary drain is successful in the majority of patients with no significant differences in outcomes when compared to laparotomy with stoma. III. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) affects cell behavior, and vice versa. How ECM changes after small bowel resection (SBR) to support adaptive cellular processes has not been described. Here we characterize changes in ECM following SBR and integrate this with concomitant transcriptional perturbations. A 50% proximal SBR or sham surgery was performed on mice. On postoperative day 7, ileal tissue was sequentially depleted of protein components to generate an ECM-enriched fraction. ECM was analyzed for protein composition using mass spectrometry with subsequent Ingenuity Pathway Analysis (IPA) to identify predicted pathways and upstream regulators. qPCR and RNA-sequencing (RNA-Seq) were performed to corroborate these predicted pathways. 3034 proteins were differentially regulated between sham and SBR, of which 95 were significant (P < 0.05). IPA analysis predicted PPARα agonism to be an upstream regulator of the observed proteomic changes (P < 0.001). qPCR and RNA-Seq with KEGG analysis confirmed significant engagement of the PPAR pathway (P < 0.05). Transcriptional signatures of adapting bowel predict subsequent ECM changes after SBR. How ECM communicates with surrounding cells to drive adaptation and vice versa merits further investigation. Our findings thus far suggest ECM supports tissue hyperplasia and altered metabolic demand following SBR. Level of evidence [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) occurs in 1 out of 2500–3000 live births. Right-sided CDHs (R-CDHs) comprise 25% of all CDH cases, and data are conflicting on outcomes of these patients. The aim of our study was to compare outcomes in patients with right versus left CDH (L-CDH). We analyzed a multicenter prospectively enrolled database to compare baseline characteristics and outcomes of neonates enrolled from January 2005 to January 2019 with R-CDH vs. L-CDH. A total of 588, 495 L-CDH, and 93 R-CDH patients with CDH were analyzed. L-CDHs were more frequently diagnosed prenatally (p = 0.011). Lung-to-head ratio was similar in both cohorts. R-CDHs had a lower frequency of primary repair (p = 0.022) and a higher frequency of need for oxygen at discharge (p = 0.013). However, in a multivariate analysis, need for oxygen at discharge was no longer significantly different. There were no differences in long-term neurodevelopmental outcomes assessed at two year follow up. There was no difference in mortality, need for ECMO, pulmonary hypertension, or hernia recurrence. In this large series comparing R to L-CDH patients, we found no significant difference in mortality, use of ECMO, or pulmonary complications. Our study supports prior studies that R-CDHs are relatively larger and more often require a patch or muscle flap for repair. Prognosis study Level II [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background Epidermal Growth Factor (EGF) reduces necrotizing enterocolitis (NEC). However, its high cost virtually prohibits clinical use. To reduce cost, soybean expressing human EGF was developed. Here we report effectiveness of soybean-derived EGF in experimental NEC. Methods Newborn rats were subjected to the NEC-inducing regimen of formula feeding and hypoxia. Formula was supplemented with extract from EGF-expressing or empty soybeans. NEC pathology was determined microscopically. Localization of tight junction proteins JAM-A and ZO-1 was examined by immunofluorescence and levels of mucosal COX-2 and iNOS mRNAs by real time PCR. Results Soybean extract amounts corresponding to 150 μg/kg/day EGF caused considerable mortality, whereas those corresponding to 75 μg/kg/day EGF were well tolerated. There was no significant difference in NEC scores between animals fed plain formula and formula supplemented with empty soybean extract. Soybean-EGF-supplemented formula at 75 μg/kg/day EGF significantly decreased NEC, attenuated dissociation of JAM-A and ZO-1 proteins from tight junctions, and reduced intestinal expression of COX-2 and iNOS mRNAs. Conclusion Supplementation with soybean-expressed EGF significantly decreased NEC in the rat model. Soybean-expressed EGF may provide an economical solution for EGF administration and prophylaxis of clinical NEC. [ABSTRACT FROM AUTHOR]

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 10 weeks. 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. [ABSTRACT FROM AUTHOR]

Background Congenital diaphragmatic hernia (CDH) is a prevalent major congenital anomaly with significant morbidity and mortality. Thirty to 40% mortality in CDH is largely attributed to pulmonary hypoplasia and pulmonary hypertension (PH). We hypothesized that the underlying genetic risk factors for hereditary PH are shared with CDH associated PH. Methods Participants were recruited as part of the Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science (DHREAMS) study, a prospective cohort of neonates with a diaphragmatic defect enrolled from 2005 to 2012. PH affected patients with available DNA for sequencing had one of the following: moderate or severe PH on echocardiography at 3 months of age; moderate of severe PH at 1 month of age with death occurring prior to the 3 month echocardiogram; or on PH medications at 1 month of age. We sequenced the coding regions of the hereditary PH genes bone morphogenetic protein receptor type II ( BMPR2 ), caveolin 1 ( CAV1 ) and potassium channel subfamily K, member 3 ( KCNK3 ) to screen for mutations. Results There were 29 CDH patients with PH including 16 males and 13 females. Sequencing of BMPR2 , CAV1 , and KCNK3 coding regions did not identify any pathogenic variants in these genes. Type of study Prognosis study Level of evidence Level IV [ABSTRACT FROM AUTHOR]

Background Multicenter clinical research studies in pediatric surgery have been largely limited to relatively small case-series and retrospective reviews because of the rarity of many of the diseases we treat and difficulty coordinating and executing multi-institutional studies. Creation of a collaborative research network can provide the needed patient population and infrastructure to perform high quality multi-institutional studies. Methods In 2013, eleven academic pediatric surgery centers within the United States formed a research consortium to develop and conduct multicenter clinical research projects to advance the practice of pediatric surgery. Results We present our process for creating, developing, and maintaining this consortium including initial regional geographic limitation, charter development with by-laws and procedures for adopting studies, and research infrastructure including a central website for study monitoring and central reliance institutional review board process. Conclusion Our model could be reproduced or adapted by other institutions to develop or strengthen other research collaboratives. Level of evidence Type of study: retrospective, IV. [ABSTRACT FROM AUTHOR]

Introduction Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. NEC severity varies widely. Recent data have demonstrated a strong link between gut microbial dysbiosis and development of NEC. We tested the hypothesis that alterations in the gut microbiome at the time of diagnosis predict the severity of NEC. Methods We used prospectively collected fecal samples from very low birth weight infants who developed NEC, stratifying by NEC severity. Fecal bacterial DNA was sequenced using 16S rRNA pyrosequencing. A generalized Wald-type test based on the Dirichlet multinomial distribution was used to test for differences in microbial communities. Results Of 489 infants at risk, 30 NEC cases had 410 fecal samples collected in the 28 days prior to the onset of NEC available for analysis. There were no differences in the pre-NEC gut microbial community between infants treated medically vs. surgically, or those with NEC totalis. Furthermore, neither treatment of NEC significantly changed the gut microbiome post-NEC among the survivors. Conclusion We found no evidence that the gut microbiome, prior to the onset of disease, differentiates the clinical course of NEC. These data suggest that factors other than the gut microbiome may dictate disease severity. Level of evidence Level 4. [ABSTRACT FROM AUTHOR]

Purpose Previously, we demonstrated enhanced adaptation after small bowel resection (SBR) in intestinal-specific retinoblastoma (Rb)-deficient mice along with elevated levels of insulin-like growth factor 2 (IGF2) expression within the villi. The purpose of this study was to verify that the insulin-like growth factor 1 receptor (IGF1R) plays a role in this phenomenon. Methods Inducible and intestinal specific Rb and IGF1R double knockout mice (iRb/IGF1R-IKO) (n = 4) and Rb single knockout mice (iRb-IKO) (n = 5) underwent 50% mid SBR. On post-operative day 28, mice were harvested, and structural adaptation was measured as changes in crypt depth and villus height. Rates of enterocyte proliferation were recorded. IGF2 expression within the remnant villi was measured via RT-PCR. Results Both iRb-IKO and iRb/IGF1R-IKO mice demonstrated enhanced adaptation with at least a 45% increase in both crypt depth and villus height in the proximal and distal remnant bowel. Both groups showed elevation of IGF2 expression in the remnant villi, but there were no differences between the two groups. Conclusion Epithelial IGF1R is dispensable for IGF2-mediated enhanced intestinal adaptation in retinoblastoma-deficient mice. Our findings suggest that IGF2 signals for enhanced adaptation in cells outside of the epithelium. Further investigation is needed to study the IGF2/IGF1R signaling interaction within the mesenchyme. Level of Evidence Animal study - not clinical. [ABSTRACT FROM AUTHOR]

Background A significant number of children with short bowel syndrome experience intestinal failure-associated liver disease. We recently demonstrated accelerated hepatic steatosis after 50% small bowel resection (SBR) in mice. Since SBR is associated with alterations in the gut microbiome, the purpose of this study was to determine whether TLR4 signaling is critical to the development of resection-associated hepatic steatosis. Methods Male C57BL6 (control) and TLR4-knockout (KO) mice underwent 50% proximal SBR. Liver sections were analyzed to obtain the percent lipid content, and Ileal sections were assessed for morphological adaptation. Intestinal TLR4 mRNA expression was measured at 7 days and 10 weeks. Results Compared to controls, TLR4 KO mice demonstrated similar weight gain and morphological adaptation after SBR. Hepatic steatosis was decreased 32-fold in the absence of TLR4. Intestinal TLR4 mRNA expression was significantly elevated 7 days after SBR. We also found that TLR4 expression in the intestine was 20-fold higher in whole bowel sections compared with isolated enterocytes. Conclusions TLR4 signaling is critical for the development of resection-associated steatosis, but not involved in intestinal adaptation after massive SBR. Further studies are needed to delineate the mechanism for TLR4 signaling in the genesis of resection-associated liver injury. Level of evidence Animal study, not clinical. [ABSTRACT FROM AUTHOR]

Massive intestinal resection is a regrettably necessary but life-saving intervention for progressive or fulminant necrotizing enterocolitis (NEC). However, the resultant short bowel syndrome (SBS) poses its own array of challenges and complications. Within hours of such an abrupt loss of intestinal length, the intestine begins to adapt. Our ability to understand this process of intestinal adaptation has proven critical in our ability to clinically treat the challenging problem of short bowel syndrome. This review first highlights key data relating to intestinal adaptation including structural and functional changes, biochemical regulation, and other factors affecting the magnitude of intestinal adaptation responses. We then focus on intestinal rehabilitation as it relates to strategies to enhance intestinal adaptation while meeting nutritional needs and preventing complications of parenteral nutrition. [ABSTRACT FROM AUTHOR]

Background Intestinal failure–associated liver disease causes significant mortality in patients with short bowel syndrome. Steatosis, a major component of intestinal failure–associated liver disease has been shown to persist even after weaning from parenteral nutrition. We sought to determine whether steatosis occurs in our murine model of short bowel syndrome and whether steatosis was affected by manipulation of the intestinal microbiome. Methods Male C57BL6 mice underwent 50% small bowel resection and orogastric gavage with vancomycin or vehicle for 10 weeks. DNA was extracted from stool samples then sequenced using 16s rRNA. Liver lipid content was analyzed. Bile acids were measured in liver and stool. Results Compared with unoperated mice, small bowel resection resulted in significant changes in the fecal microbiome and was associated with a >25-fold increase in steatosis. Oral vancomycin profoundly altered the gut microbiome and was associated with a 15-fold reduction in hepatic lipid content after resection. There was a 17-fold reduction in fecal secondary bile acids after vancomycin treatment. Conclusion Massive small bowel resection in mice is associated with development of steatosis and prevented by oral vancomycin. These findings implicate a critical role for gut bacteria in intestinal failure–associated liver disease pathogenesis and illuminate a novel, operative model for future investigation into this important morbidity. [ABSTRACT FROM AUTHOR]

Purpose We aim to investigate the postoperative outcomes, bowel habits and quality of life (QoL) of younger pediatric ulcerative colitis (UC) patients following surgical intervention compared to an older pediatric population. Methods Medical records of UC patients after colectomy with ileoanal reconstruction (2002–2013) at our institution were reviewed. Patients/parents completed a QoL, bowel habits and disease course questionnaire. Surgical outcomes, bowel habits and QoL were reported comparing the younger (≤ 11 years old, n = 26) to older (> 11 years old, n = 38) cohorts. Results The mean age at colectomy was 7.04 ± 0.63 years vs 14.71 ± 0.32 years in the two groups. Patients had a significant (P < 0.001) reduction in stooling frequency after surgery in both age groups and had favorable rates of fecal continence. The frequency of pouchitis and postoperative small bowel obstruction was similar in both cohorts. Dehydration was slightly increased in the younger population but not significant. Anastomotic leak and stricture rates were slightly reduced in younger patients. Postoperative QoL was favorable and similar regardless of age at surgery. Conclusions Colectomy with ileoanal anastomosis for young children (≤ 11 years old) with UC is without increased complications relative to older patients and maintains a postoperative QoL and stool patterns. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to determine the early impact of American College of Surgeons (ACS)-level-1 verification at an established pediatric trauma center. Methods Following IRB approval, we conducted a retrospective review of all trauma patients treated at a level-1 state-designated pediatric trauma center, comparing 2 years before (2009-2010) and 2 years after ACS-verification (mid-2012-mid-2014). Statistical significance was defined as p < 0.05. Results Before verification, 2105 trauma patients were admitted to our institution compared to 2248 patients admitted after ACS-verification. Overall, there were no differences in mean age or injury severity score (ISS). Hospital and pediatric intensive care unit (PICU) length of stay (LOS), ventilator days, and mortality were also unchanged. Through incorporation of clinical pathways, the number of PICU admissions decreased significantly from 17.2% to 13.7%. Morbidity in the form of hospital-acquired conditions (HACS) also decreased following verification, most notably through reduction in pneumonias. Decubitus ulcers and nosocomial infections reached their nadir by 2014. Hospital readmission rates also decreased. Conclusions ACS-verification at a level-1 pediatric trauma center is associated with an immediate benefit to patient outcomes. Enhanced tracking and institutional policy changes resulted in fewer HACS. Further cost-saving and improved outcomes because of ACS-verification may be amplified over time. [ABSTRACT FROM AUTHOR]

Purpose Intestinal adaptation involves villus lengthening, crypt deepening, and increased capillary density following small bowel resection (SBR). Mice lacking the proangiogenic chemokine CXCL5 have normal structural adaptation but impaired angiogenesis. This work evaluates the impact of incomplete adaptive angiogenesis on the functional capacity of the intestine after SBR. Methods CXCL5 knockout (KO) and C57BL/6 wild-type (WT) mice underwent 50% SBR. Magnetic resonance imaging measured weekly body composition. Intestinal absorptive capacity was evaluated through fecal fat analysis. Gene expression profiles for select macronutrient transporters were measured via RT-PCR. Postoperative crypt and villus measurements were assessed for structural adaptation. Submucosal capillary density was measured through CD31 immunohistochemistry. Results Comparable postoperative weight gain occurred initially. Diminished weight gain, impaired fat absorption, and elevated steatorrhea occurred in KO mice after instituting high-fat diet. Greater postoperative upregulation of ABCA1 fat transporter occurred in WT mice, while PEPT1 protein transporter was significantly downregulated in KO mice. KO mice had impaired angiogenesis but intact structural adaptation. Conclusion After SBR, KO mice display an inefficient intestinal absorption profile with perturbed macronutrient transporter expression, impaired fat absorption, and slower postoperative weight gain. In addition to longer villi and deeper crypts, an intact angiogenic response may be required to achieve functional adaptation to SBR. [ABSTRACT FROM AUTHOR]

Purpose Intestinal adaptation structurally represents increases in crypt depth and villus height in response to small bowel resection (SBR). Previously, we found that neither epidermal growth factor receptor (EGFR) nor insulin-like growth factor 1 receptor (IGF1R) function was individually required for normal adaptation. In this study, we sought to determine the effect of disrupting both EGFR and IGF1R expression on resection-induced adaptation. Methods Intestinal-specific EGFR and IGF1R double knockout mice (EGFR/IGF1R-IKO) (n = 6) and wild-type (WT) control mice (n = 7) underwent 50% proximal SBR. On postoperative day (POD) 7, structural adaptation was scored by measuring crypt depth and villus height. Rates of crypt cell proliferation, apoptosis, and submucosal capillary density were also compared. Results After 50% SBR, normal adaptation occurred in both WT and EGFR/IGF1R-IKO. Rates of proliferation and apoptosis were no different between the two groups. The angiogenic response was less in the EGFR/IGF1R-IKO compared to WT mice. Conclusion Disrupted expression of EGFR and IGF1R in the intestinal epithelial cells does not affect resection-induced structural adaptation but attenuates angiogenesis after SBR. These findings suggest that villus growth is driven by receptors and pathways that occur outside the epithelial cell component, while angiogenic responses may be influenced by epithelial-endothelial crosstalk. [ABSTRACT FROM AUTHOR]

Background: The factors that contribute to success as a pediatric surgeon–scientist are not well defined. The purpose of this study is to define a group of NIH-funded pediatric surgeons, assess their academic productivity, and elucidate factors that have contributed to their success. Methods: Pediatric surgeons were queried in the NIH report database to determine NIH funding awarded. Academic productivity was then assessed. An online survey was then targeted to NIH-funded pediatric surgeons. Results: Since 1988, 83 pediatric surgeon–investigators have received major NIH funding. Currently, there are 37 pediatric surgeons with 43 NIH-sponsored awards. The mean h -index of this group of pediatric surgeons was 18 ± 1.1, mean number of publications (since 2001) was 21 ± 2.1, and both increase commensurate with academic rank. In response to the survey, 81% engaged in research during their surgical residency, and 48% were mentored by a pediatric surgeon–scientist. More than 60% of respondents had significant protected time and financial support. Factors felt to be most significant for academic success included mentorship, perseverance, and protected time. Conclusions: Mentorship, perseverance, institutional commitment to protected research time, and financial support are considered to be important to facilitate the successes of pediatric surgeon–scientists. These results will be useful to aspiring pediatric surgeon–scientists and departments wishing to develop a robust research program. [ABSTRACT FROM AUTHOR]

Introduction: Short bowel syndrome (SBS) is a morbid clinical condition that results from massive small-bowel resection (SBR). After SBR, there is a dramatic weight loss in the acute postoperative period. Our aim was to determine the impact of a high-protein diet (HPD) on weight gain and body composition in mice after SBR. Methods: C57BL/6 mice underwent 50 % proximal SBR. Postoperatively, mice were randomly selected to receive standard rodent liquid diet (LD) ( n = 6) or an isocaloric HPD ( n = 9) for 28 days. Mice weights were recorded daily. Body composition analyses were obtained weekly. Student's t test was used for statistical comparisons with p < 0.05 considered significant. Results: Mice that were fed HPD after SBR returned to baseline weight on average at postoperative day (POD) 8 versus mice that were fed LD that returned to baseline weight on average at POD 22. Total fat mass and lean mass were significantly greater by POD 14 within the HPD group. Both groups of mice demonstrated normal structural adaptation. Conclusion: HPD results in greater weight gain and improved body composition in mice after SBR. This finding may be clinically important for patients with SBS since improved weight gain may reduce the time needed for parenteral nutrition. [ABSTRACT FROM AUTHOR]

Previously, we have demonstrated that genetically disrupting retinoblastoma protein (Rb) expression in enterocytes results in taller villi, mimicking resection-induced adaption responses. Rb deficiency also results in elevated insulin-like growth factor-2 (IGF-2) expression in villus enterocytes. We propose that postoperative disruption of Rb results in enhanced adaptation which is driven by IGF-2. Inducible, intestine-specific Rb-null mice (iRbIKO) and wild-type (WT) littermates underwent a 50 % proximal small-bowel resection (SBR) at 7-9 weeks of age. They were then given tamoxifen on postoperative days (PODs) 4-6 and harvested on POD 28. The experiment was then repeated on double knockouts of both IGF-2 and Rb (IGF-2 null/iRbIKO). iRbIKO mice demonstrated enhanced resection-induced adaptive villus growth after SBR and increased IGF-2 messenger RNA (mRNA) in ileal villus enterocytes compared to their WT littermates. In the IGF-2 null/iRbIKO double-knockout mice, there was no additional villus growth beyond what was expected of normal resection-induced adaptation. Adult mice in which Rb is inducibly deleted from the intestinal epithelium following SBR have augmented adaptive growth. IGF-2 expression is necessary for enhanced adaptation associated with acute intestinal Rb deficiency. [ABSTRACT FROM AUTHOR]

Background After massive small bowel resection (SBR), a postoperative diet high in fat is associated with enhanced villus growth. The purpose of this study was to further elucidate the quantity and composition of enteral fat in structural and metabolic changes after SBR. Methods C57/Bl6 mice underwent a 50% proximal SBR. Mice were then randomized to receive a low-fat diet (12% kcal fat), medium-fat diet (44% kcal fat), or high-fat diet (HFD; 71% kcal fat) ad libitum. In a separate experiment, mice underwent 50% proximal SBR and then were randomized to liquid diets of 42% kcal of fat in which the fat was composed of menhaden oil, milk fat, or olive oil. After 2 weeks, mice underwent body composition analysis and the small intestine was harvested. Results Mice that ingested the greatest amount of enteral fat (HFD) had the greatest percent lean mass. When the effects of the different kinds of enteral fat were analyzed, mice that consumed menhaden oil had the greatest percent lean mass with the greatest overall retention of preoperative weight. Conclusion These findings suggest that enteral fat enriched in omega-3 fatty acids may offer clinically relevant metabolic advantages for patients with short gut syndrome. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Intestinal adaptation is the compensatory response to massive small bowel resection (SBR) and characterized by lengthening of villi and deepening of crypts, resulting in increased mucosal surface area. Previous studies have demonstrated increased villus capillary blood vessel density after SBR, suggesting a role for angiogenesis in the development of resection-induced adaptation. Since we have previously shown enhanced expression of the proangiogenic chemokine CXCL5 after SBR, the purpose of this study was to determine the effect of disrupted CXCL5 expression on intestinal adaptation. Methods: CXCL5 knockout (KO) and C57BL/6 wild type (WT) mice were subjected to either a 50% proximal SBR or sham operation. Ileal tissue was harvested on postoperative day 7. To assess for adaptation, villus height and crypt depth were measured. Submucosal capillary density was measured by CD31 immunohistochemistry. Results: Both CXCL5-KO and WT mice demonstrated normal structural features of adaptation. Submucosal capillary density increased in the WT but not in the KO mice following SBR. Conclusion: CXCL5 is required for increased intestinal angiogenesis during resection-induced adaptation. Since adaptive villus growth occurs despite impaired CXCL5 expression and enhanced angiogenesis, this suggests that the growth of new blood vessels is not needed for resection-induced mucosal surface area expansion following massive SBR. [Copyright &y& Elsevier]

Abstract: Purpose: Enhanced structural features of resection-induced intestinal adaptation have been demonstrated following the administration of multiple different growth factors and peptides. Among these, the insulin-like growth factor (IGF) system has been considered to be significant. In this study, we employ mutant mouse strains to directly test the contribution of IGF2 and its enterocyte receptor (IGF1R) toward the adaptation response to massive small bowel resection (SBR). Methods: IGF2-knockout (IGF2-KO) (n=8) and intestine specific IGF1R-knockout mice (IGF1R-IKO) (n=9) and their wild type (WT) littermates (n=5, n=7, respectively) underwent 50% proximal SBR. At post-operative day 7, structural adaptation was measured as crypt depth and villus height. Rates of enterocyte proliferation and apoptosis were also recorded. Results: The successful deletion of IGF2 and IGF1R expression in the enterocytes was confirmed by RT-PCR and Western blot, respectively. Normal adaptation occurred in both IGF2-KO and IGF1R-IKO mice after 50% SBR. Post-operative rates of proliferation and apoptosis in both IGF2-KO and IGF1R-IKO mice were no different than their respective controls. Conclusion: IGF2 and functional IGF1R signaling in enterocytes are both dispensable for resection-induced adaptation responses. The mechanism for IGF-stimulation of intestinal adaptation may involve other ligands or cellular compartments within the intestine. [Copyright &y& Elsevier]

Previous studies have shown that high-fat diet (HFD) enhances adaptation if provided immediately following small bowel resection (SBR). The purpose of this study was to determine if HFD could further enhance villus growth after resection-induced adaptation had already taken place. C57/Bl6 mice underwent a 50 % proximal SBR or sham operation and were then provided a standard rodent liquid diet (LD) ad lib. After a typical period of adaptation (7 days), SBR and sham-operated mice were randomized to receive either LD or HFD (42 % kcal fat) for an additional 7 days. Mice were then harvested, and small intestine was collected for analysis. Adaptation occurred in both SBR groups; however, the SBR/HFD had significantly increased villus height compared to SBR/LD. Reverse transcription-polymerase chain reaction of villus enterocytes showed a marked increase in CD36 expression in the SBR/HFD group compared with SBR/LD mice. While exposure to increased enteral fat alone did not affect villus morphology in sham-operated mice, HFD significantly increased villus growth in the setting of resection-induced adaptation, supporting the clinical utility of enteral fat in augmenting adaptation. Increased expression of CD36 suggests a possible mechanistic role in dietary fat metabolism and villus growth in the setting of short gut syndrome. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: We have previously demonstrated a hyperplastic phenotype when Rb expression was disrupted within the intestinal epithelium. These findings mimic resection-induced adaptation suggesting a possible mechanistic role for Rb during adaptation. The purpose of the present study was to elucidate a mechanism for how Rb deficiency induces intestinal hyperplasia. Methods: Enterocytes isolated from intestine-specific Rb knockout mice (Rb-IKO) underwent a microarray to elucidate their gene expression profile. IGF2 expression was significantly elevated, which was subsequently confirmed by RT-PCR and in situ mRNA hybridization. Mice with deficient expression of IGF2 or its receptor IGF1R were therefore crossed with Rb-IKO mice to determine the significance of IGF2 in mediating the Rb-IKO intestinal phenotype. Results: Expression of IGF2 was significantly elevated in villus enterocytes of Rb-IKO mice. The mucosal hyperplasia in Rb-IKO mice was reversed when either IGF2 or IGF1R expression was genetically disrupted in Rb-IKO mice. Conclusion: IGF-2 expression is significantly elevated in villus enterocytes and is required for the hyperplastic intestinal mucosal phenotype of Rb-IKO mice. The trophic effects of IGF2 require intact IGF1R signaling within the intestinal epithelium. These findings reveal novel regulatory roles for Rb in expanding intestinal mucosal surface area. [Copyright &y& Elsevier]

Abstract: Purpose: Massive small bowel resection (SBR) results in an adaptive response within the remnant bowel. We have previously shown an immediate reduction in intestinal blood flow and oxygen saturation (sO2) after SBR. We therefore sought to determine the duration of resection-induced intestinal hypoxia and expression of hypoxia-inducible factors (HIFs) following SBR. Methods: C57B6 mice were subjected to 50% proximal SBR or a sham procedure. Photoacoustic microscopy (PAM) was used to measure blood flow and sO2 on postoperative days (PODs) 1, 3, and 7. Ileal tissue was harvested 6h postoperatively and on PODs 1 and 2, and HIF1α, HIF2α, and VEGF mRNA expression were assessed via RT-PCR. A p value of less than 0.05 was considered significant. Results: Following SBR, reduction in intestinal blood flow persists for 24h and is followed with hyperemia by POD 3. The immediate reduction in venous sO2 and increased tissue oxygen utilization continued through POD 7. Enhanced expression of HIF1α was demonstrated 6h following SBR. Conclusion: Massive SBR results in an immediate relative hypoxic state within the remnant bowel with early enhanced expression of HIF1α. On POD 7, increased tissue oxygen extraction and elevated blood flow persist in the adapting intestine. [Copyright &y& Elsevier]

Abstract: Necrotizing enterocolitis (NEC) is a devastating intestinal disease resulting in major neonatal morbidity and mortality. The pathology is poorly understood, and the means of preventing and treating NEC are limited. Several endogenous growth factors have been identified as having important roles in intestinal growth as well as aiding intestinal repair from injury or inflammation. In this review, we will discuss several growth factors as mediators of intestinal regeneration and repair as well as potential therapeutic agents for NEC. [Copyright &y& Elsevier]

Abstract: Adaptation is an important compensatory response to environmental cues resulting in enhanced survival. In the gut, the abrupt loss of intestinal length is characterized by increased rates of enterocyte proliferation and apoptosis and culminates in adaptive villus and crypt growth. In the development of an academic pediatric surgical career, adaptation is also an important compensatory response to survive the ever changing research, clinical, and economic environment. The ability to adapt in both situations is critical for patients and a legacy of pediatric surgical contributions to advance our knowledge of multiple conditions and diseases. [Copyright &y& Elsevier]

Abstract: Purpose: Intestinal adaptation after massive small bowel resection (SBR) permits improved absorption of enteral nutrition despite significant loss of bowel length. Epidermal growth factor (EGF) and its receptor (EGFR) have previously been established to play major roles in the pathogenesis of adaptation. This study tested the hypothesis that EGFR signaling within the epithelial cell compartment (enterocytes) is required for intestinal adaptation. Methods: We developed a tamoxifen-inducible Villin-Cre/LoxP recombinant system for enterocyte-directed EGFR deletion using EGFR-floxed mice. Epidermal growth factor receptor–null mice and wild-type littermates underwent either 50% proximal SBR or sham operation. Ileal tissue was harvested on postoperative day 7. To assess for adaptation, villus height and crypt depth as well as rates of crypt cell proliferation and apoptosis were measured. Results: Adaptation after SBR occurred normally, as demonstrated by significant increases in villus height, crypt depth, and crypt proliferative and apoptotic index in both the wild-type and EGFR-null mice. Conclusion: Enterocyte EGFR expression is not required for the adaptation response to massive SBR. This novel finding suggests that enterocyte proliferation during adaptation is regulated by EGFR signaling in cells other than enterocytes, perhaps within the mesenchymal cell compartment of the bowel wall via factor(s) that are presently unknown. [Copyright &y& Elsevier]

Background: p38-Alpha mitogen-activated protein kinase (p38-MAPK) is a tumor suppressor often mutated in human cancers, but its specific role in colorectal cancer is not completely understood. Previous studies have found that p38-MAPK activity inhibits epithelial proliferation and promotes apoptosis in the intestine. Therefore, we sought to test the hypothesis that intestinal disruption of p38-MAPK would lead to increased tumorigenesis in the colon. Methods: p38-MAPK was deleted in mice within the intestinal epithelium using a tamoxifen-inducible Cre system under control of the villin promoter [villin-Cre ERT2(+), MAPK14(f/f)]. An azoxymethane and dextran sodium sulfate protocol was used to drive intestinal tumor development. Tumor measurements were made using computer software from photographs of excised colon specimens. Results: The number of mice that developed tumors was not statistically different when comparing wild-type mice (7/14) to inducible, intestine epithelial-deleted p38-MAPK (9/11) mice after azoxymethane/dextran sodium sulfate treatment (P = .21). However, the epithelial-deleted p38-MAPK mice developed significantly more tumors (3.7 vs 1.1; P = .008) and nearly 4 times the total tumor burden as wild-type mice (17.4 vs 4.8 mm2; P = .03). Wild-type and epithelial-deleted p38-MAPK groups demonstrated a similar degree of colon inflammation. Conclusion: Deletion of p38-MAPK within the colonic mucosa leads to a hyperplastic state promoting greater tumor development. Because the severity of colitis was not augmented in mice with p38-MAPK deficiency, tumor development is likely mediated by impaired cell cycle regulation within the colonic epithelium. Manipulation of p38-MAPK activity may provide a novel treatment and/or prevention strategy in the management of colorectal cancer, particularly in the setting of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Massive small bowel resection (SBR) results in villus angiogenesis and a critical adaptation response within the remnant bowel. Previous ex vivo studies of intestinal blood flow after SBR are conflicting. We sought to determine the effect of SBR on intestinal hemodynamics using photoacoustic microscopy, a noninvasive, label-free, high-resolution in vivo hybrid imaging modality. Methods: Photoacoustic microscopy was used to image the intestine microvascular system and measure blood flow and oxygen saturation (So 2) of the terminal mesenteric arteriole and accompanying vein in C57BL6 mice (n = 7) before and immediately after a 50% proximal SBR. A P value of less than .05 was considered significant. Results: Before SBR, arterial and venous So 2 were similar. Immediately after SBR, the venous So 2 decreased with an increase in the oxygen extraction fraction. In addition, the arterial and venous blood flow significantly decreased. Conclusion: Massive SBR results in an immediate reduction in intestinal blood flow and increase in tissue oxygen utilization. These physiologic changes are observed throughout the remnant small intestine. The contribution of these early hemodynamic alterations may contribute to the induction of villus angiogenesis and the pathogenesis of normal intestinal adaptation responses. [Copyright &y& Elsevier]

Abstract: Purpose: Our goal is to identify the impact of time to surgical intervention on the outcomes of infants with gastroschisis. Methods: After institutional review board approval, we performed a retrospective review of the medical records of all infants admitted to our institution from 2001 to 2010. Transport, bowel stabilization, and closure times were defined as the time from birth to admission, admission to the first-documented operative intervention, and first operative intervention to abdominal closure, respectively. Outcomes included age at full enteral feeds, total parental nutrition days, ventilator days, and hospital length of stay. Multivariate analysis was used to identify independent predictors of the outcomes. Results: One hundred eighteen infants with gastroschisis were included in our study. Transport and bowel stabilization times were not predictive of any outcome. However, the time to abdominal wall closure and postnatal gastrointestinal complications were independently predictive of age at full enteral feeds, total parenteral nutrition days, and hospital length of stay. Conclusion: Time to surgical evaluation/bowel stabilization was not predictive of any clinically relevant outcomes in infants with gastroschisis. These data demonstrate that potential benefits from prenatal regionalization of infants with gastroschisis are not supported by decreased time to operative intervention. [Copyright &y& Elsevier]

Background: Adaptation following massive intestinal loss is characterized by increased villus height and crypt depth. Previously, we demonstrated that p21-null mice do not adapt after small bowel resection (SBR). As retinoblastoma protein (Rb) levels are elevated in p21-null crypt cells, we first sought to determine whether Rb is required for normal adaptation. Next, we tested whether Rb expression is responsible for blocked adaptation in p21-nulls. Methods: Genetically manipulated mice and wild-type (WT) littermates underwent either 50% SBR or sham operation. The intestine was harvested at 3, 7, or 28 days later and intestinal adaptation was evaluated. Enterocytes were isolated and protein levels evaluated by Western blot and quantified by optical density. Results: Rb-null mice demonstrated increased villus height, crypt depth, and proliferative rate at baseline, but there was no further increase following SBR. Deletion of one Rb allele lowered Rb expression and restored resection-induced adaptation responses in p21-null mice. Conclusion: Rb is specifically required for resection-induced adaptation. Restoration of adaptation in p21-null mice by lowering Rb expression suggests a crucial mechanistic role for Rb in the regulation of intestinal adaptation by p21. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The aim of the study was to compare the cost-effectiveness of different imaging strategies for the diagnosis of pediatric intussusception using a decision analytic model. Methods: A Markov decision model was constructed to model effects of radiation exposure at the time of intussusception in a hypothetical cohort of 2-year-old children. The 2 strategies compared were ultrasound followed conditionally by contrast enema (US/CE) vs contrast enema (CE) alone. The model simulated short-term and long-term outcomes of the patients, calculating the average quality-adjusted life years (QALYs) and health care costs associated with each arm. Results: The use of ultrasound as a first-line diagnostic modality would result in a decrease of 79.3 and 59.7 cases of radiation-induced malignancy per 100,000 male and female children evaluated, respectively. For male and female children with intussusception, US/CE was both the most costly initial imaging strategy and the most effective compared with CE. The incremental cost-effectiveness ratios of US/CE to CE was $70,100 (boy) and $92,227 (girl) per quality-adjusted life years gained. Conclusions: In a Markov decision model of pediatric acute intussusception, initial US/CE was both the most costly and the most effective strategy. [Copyright &y& Elsevier]

Abstract: Purpose: The objective of our study was to quantify mucosal bacterial DNA within specimens from neonates undergoing small bowel resection for necrotizing enterocolitis (NEC). Methods: We obtained clinical information and pathologic specimens from all infants diagnosed with NEC who underwent surgical treatment at our institution from 1999 to 2008. Bacterial and human DNA were isolated from paraffin-embedded surgical specimens, and real time polymerase chain reaction was used to amplify bacterial and human genes. Linear regression was used to quantify the amount of human and bacterial DNA in our specimens. Results: From a cohort of 50 infants, we identified 23 infants who underwent both surgical resection and subsequent intestinal reanastomosis. Thirteen (59%) of the neonates had Bell stage III NEC, and 9 (41%) had stage II. There was significantly more bacterial DNA in the resection specimens than in the reanastomosis specimens. This corresponds to a median (interquartile range) increase of 1.81 (1.11-4.69)-fold bacterial DNA in the resection specimen compared with the reanastomosis specimen (P < .05). Conclusion: There is more bacterial DNA in infants with acute NEC compared with the same infants after the NEC had clinically resolved. These findings underscore the potential relevance of adherent or invasive bacteria across the bowel wall in the pathogenesis of NEC. [Copyright &y& Elsevier]

Abstract: Purpose: In animal models, the small intestine responds to massive small bowel resection (SBR) through a compensatory process termed adaptation, characterized by increases in both villus height and crypt depth. This study seeks to determine whether similar morphologic alterations occur in humans after SBR. Methods: Clinical data and pathologic specimens of infants who had both an SBR for necrotizing enterocolitis and an ostomy takedown from 1999 to 2009 were reviewed. Small intestine mucosal morphology was compared in the same patients at the time of SBR and at the time of ostomy takedown. Results: For all samples, there was greater villus height (453.6 ± 20.4 vs 341.2 ± 12.4 μm, P < .0001) and crypt depth (178.6 ± 7.2 vs 152.6 ± 6 μm, P < .01) in the ostomy specimens compared with the SBR specimens. In infants with paired specimens, there was an increase of 31.7% ± 8.3% and 22.1% ± 10.0% in villus height and crypt depth, respectively. There was a significant correlation between the amount of intestine resected and the percent change in villus height (r = 0.36, P < .05). Conclusion: Mucosal adaptation after SBR in human infants is similar to what is observed in animal models. These findings validate the use of animal models of SBR used to understand the molecular mechanisms of this important response. [Copyright &y& Elsevier]

Abstract: Introduction: Pouchograms are used to assess the integrity of the ileal pouch anal anastomosis (IPAA) in patients who have undergone restorative proctocolectomy. Its benefits have been questioned, and there are no data to support the routine use in children. Methods: We retrospectively reviewed the charts of 26 patients who had an IPAA and pouchogram at our institution between 2001 and 2009. Each patient also underwent an examination under anesthesia to assess the integrity of the IPAA on the day of the ileostomy closure. Results: The mean age of the patients was 13.8 (±0.7) years. The pouchogram was performed at a median of 6 weeks after the IPAA (range, 4-20 weeks). The findings were normal in 26 (89.7%) and demonstrated stricture in 2 (6.9%) and leak in 1 (3.4%). History was suggestive and physical examination was confirmatory in these 3 problematic cases. Conclusions: A contrast enema is not routinely required to evaluate the integrity of the IPAA before ileostomy reversal in pediatric patients. Complications can be detected by history and rectal examination before ileostomy closure. We recommend the use of contrast enema only in symptomatic patients where a leak is suspected, thereby limiting radiation exposure and inconvenience. [Copyright &y& Elsevier]

Background: Adaptive villus growth after a massive small bowel resection (SBR) is an important response to the loss of intestinal surface area and is regulated via epidermal growth factor receptor (EGFR) signaling. Increased levels of the proangiogenic chemokine ligand 5 (CXCL5) have been found within the adapting bowel in which angiogenesis is increased. We sought to determine whether CXCL5 was expressed specifically in the villus mesenchymal zone (area of increased blood vessel growth) and whether this expression was affected by EGF. Methods: C57BL/6J mice were subjected to sham operation (bowel transaction with reanastomosis) or 50% proximal SBR. The remnant intestine was harvested, and the villus lamina propria was isolated by laser capture microdissection. The expression of CXCL5 messenger RNA (mRNA) was analyzed using real-time polymerase chain reaction (RT-PCR). Furthermore, CXCL5 mRNA levels were determined in EGF-stimulated human umbilical vein endothelial cells (HUVECs). Results: A 2.39-fold increase (P < .05) in CXCL5 mRNA occurred in the lamina propria after SBR. In addition, villus height was found to be related directly to the degree of CXCL5 mRNA (R 2 = 0.97) expression. HUVECs treated with EGF demonstrated a 9-fold increase in CXCL5 mRNA expression. Conclusion: The villus growth observed in resection-induced adaptation is associated with increased expression of the chemokine CXCL5 within the lamina propria. Because EGF enhances CXCL5 expression directly in endothelial cells, EGFR-directed proangiogenic gene expression may be a critical mechanism for adaptive ileal villus growth. [Copyright &y& Elsevier]

Abstract: Purpose: The magnitude of intestinal adaptation is considered to correlate with the extent of small bowel resection (SBR). However, this association has never been tested in mice. We sought to test the hypothesis that a greater SBR will induce a greater adaptation response. Methods: C57/B6 mice underwent 50% SBR, 75% SBR, or sham operation and were killed on postoperative day 7. The magnitude of adaptation was compared between 50% SBR and 75% SBR as changes in villus height, crypt depth, as well as rates of apoptosis and proliferation. Results: Seventy-five percent SBR led to decreased survival and increased weight loss compared with 50% SBR. The remnant ileum of both 50% SBR and 75% SBR displayed similar crypt expansion, enhanced villi, and increased apoptotic indices. Proliferation rates increased after 50% and 75% SBR equally. Conclusion: Models of resection greater than 50% in mice result in greater morbidity and mortality and do not magnify the adaptation response to massive SBR. The use of more extreme resection models does not appear to provide added benefit for investigating mechanisms of intestinal adaptation. [Copyright &y& Elsevier]