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Background & Aims: Intestinal rehabilitation is the preferred treatment for children with short bowel syndrome (SBS) whatever the residual bowel length, and depends on the accurate management of long-term parenteral nutrition (PN). If nutritional failure develops, intestinal transplantation (ITx) should be discussed and may be life-saving. This study aimed to evaluate survival, PN dependency and nutritional status in children with neonatal very SBS on PN or after ITx, in order to define indications and timing of both treatments., Patients and Methods: This retrospective cross-sectional study enrolled 36 children with very SBS (<40 cm) who entered our intestinal rehabilitation program from 1987 to 2007., Results: All the children on long-term PN (n = 16) survived with a follow-up of 17 years (9-20). Six of them were eventually weaned off PN. Twenty children underwent ITx: eight children died (40%) 29 months (0-127) after Tx. The others 12 patients were weaned off PN 73 days (13-330) after Tx. Follow-up after transplantation was 14 years (6-28). Seven out of 8 (88%) patients with a history of gastroschisis required ITx. Patients who required ITx had longer stoma duration., Conclusion: Survival rate of children with very short bowel was excellent if no life-threatening complications requiring transplantation developed. Gastroschisis and delayed ostomy closure are confirmed as risk factor for nutritional failure. Intestinal rehabilitation may allow a total weaning of PN before adulthood. A follow-up by a multidisciplinary team is necessary to avoid PN complications in order to minimize indications for ITx., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Bowel healing is an important goal of therapy for patients with Crohn's disease (CD). Although there have been many studies of mucosal healing, transmural healing (ie, in the bowel wall) has not been investigated in children. We analyzed data from the ImageKids study to determine associations among mucosal, transmural healing and levels of calprotectin and C-reactive protein in children with CD., Methods: We collected data from a multi-center study designed to develop 2 magnetic resonance enterography (MRE)-based measures for children with CD (6-18 years old). In our analysis of 151 children (mean age, 14.2 ± 2.4 years), all patients underwent MRE and a complete ileocolonoscopic evaluation; fecal levels of calprotectin and blood levels of C-reactive protein were measured. Mucosal healing was defined as simple endoscopic severity index in CD score below 3, transmural healing as an MRE visual analogue score below 20 mm, and deep healing as a combination of transmural and mucosal healing., Results: We identified mucosal healing with transmural inflammation in 9 children (6%), transmural healing with mucosal inflammation in 38 children (25%), deep healing in 21 children (14%), and mucosal and transmural inflammation in 83 children (55%). The median level of calprotectin was lowest in children with deep healing (mean level, 10 μg/g; interquartile range, 10-190 μg/g), followed by children with either transmural or mucosal inflammation, and highest in children with mucosal and transmural inflammation (810 μg/g; interquartile range, 539-1737 μg/g) (P < .001). Fecal level of calprotectin identified children with deep healing with an area under the receiver operating characteristic curve value of 0.93 (95% CI, 0.89-0.98); level of C-reactive protein identified children with deep healing with an area under the receiver operating characteristic curve value of 0.81 (95% CI, 0.71-0.9). A calprotectin cutoff value of 100 μg/g identified children with deep healing with 71% sensitivity and 92% specificity; a cutoff value of 300 μg/g identified children with mucosal healing with 80% sensitivity and 81% specificity., Conclusions: In a prospective study of children with CD, we found that one-third have healing in only the mucosa or the bowel wall (not both). Levels of fecal calprotectin below 300 μg/identify children with mucosal healing, but a lower cutoff value (below 100 μg/g) is needed to identify children with deep healing. Clinicaltrials.gov no: NCT01881490., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Chronic intestinal failure (CIF) requires long term parenteral nutrition (PN) and, in some patients, intestinal transplantation (ITx). Indications and timing for ITx remain poorly defined. In the present study we aimed to analyze causes and outcome of children with CIF., Methods: 118 consecutive patients referred to our institution were assessed by a multidisciplinary team and four different categories were defined retrospectively based on their clinical course: Group 1: patients with reversible intestinal failure; group 2: patients unsuitable for ITx, group 3: patients listed for ITx; group 4: patients stable under PN. Analysis involved comparison between groups for nutritional status, central venous catheter (CVC) related complications, liver disease, and outcome after transplantation by using non parametric tests, Mann-Whitney tests, Kruskal-Wallis, Wilcoxon signed rank tests and chi square distribution for percentage., Results: 118 children (72 boys) with a median age of 15 months at referral (2 months-16 years) were assessed. Etiology of IF was short bowel syndrome [n = 47], intractable diarrhea of infancy [n = 37], total intestinal aganglionosis [n = 18], and chronic intestinal pseudoobstruction [n = 17]. Most patients (89.8%) were totally PN dependent, with 48 children (40.7%) on home-PN prior to admission. Nutritional status was poor with a median body weight at -1.5 z-score (ranges: -5 to +2.5) and median length at -2.0 z-score (ranges: -5.5 to +2.3). The mean number of CVC inserted per patient was 5.2 (range 1-20) and the mean number of CRS per patient was 5.5 (median: 5; range 0-12) Fifty-five patients (46.6%) had thrombosis of ≥2 main venous axis. At admission 34.7% of patients had elevated bilirubin (≥50 μmol/l), and 19.5% had platelets <100,000/ml, and 15% had both. Liver biopsy performed in 79 children was normal (n = 4), or showed F1 or F2 fibrosis (n = 29), bridging fibrosis F3 (n = 20), or cirrhosis (n = 26). Group 1 included 10 children finally weaned from PN (7-years survival: 100%). Group 2 included 12 children with severe liver disease and associated disorders unsuitable for transplantation (7-years survival: 16.6%). Group 3 included 66 patients (56%) who were listed for small bowel or liver-small bowel transplantation, 62/66 have been transplanted (7 years survival: 74.6%). Factors influencing outcome after liver-ITx were body weight (p < .004), length (p < .001), pre-Tx bilirubin plasma level (p < .001) and thrombosis (p < .01) for isolated ITx, Group 4 included 30 children (25.4%) with irreversible IF considered as potential candidates for isolated ITx. Four children were lost from follow up and 3 died within 2 years (survival 88.5%). Among potential candidates, the following parameters improved significantly during the first 12 months of follow up: Body weight (p.0001), length (p < .0001) and bilirubin (p < .0001)., Conclusions: many patients had a poor nutritional status with severe complications especially liver disease. PN related complications were the most relevant indication for ITx, but also a negative predictor for outcome. Early patient referral for Tx-assessment might help to identify and separate children with irreversible IF from children with transient IF or uncomplicated long-term PN, allowing to adapt a patient-based treatment strategy including or not ITx., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: Anastomotic ulceration (AU) is a rare complication after intestinal resection and anastomosis, described mostly in children. The main symptom is occult bleeding, leading to iron-deficiency anemia, which is life threatening., Methods: The present survey reports a series of patients with AU after intestinal resection in infancy, focusing on predictive factors, medical and surgical treatment options, and long-term outcomes. Eleven patients (7 boys) born between 1983 and 2005 with AU after an intestinal resection and anastomosis in infancy were included in this retrospective review., Results: The diagnosis of AU was often delayed for several years. No predictive factor (including the primary disease, the length of the remnant bowel, and the loss of the ileocaecal valve) could be identified. Numerous treatment options, including antibiotics and anti-inflammatory drugs, proved to be ineffective to induce prolonged remission. Even after surgical resection, relapses were observed in 5/7 children., Conclusions: The mechanism leading to AU remains unknown. Contrary to previous reports with limited follow-up, no medical or surgical treatment could prevent recurrences. Because relapses may occur several years after treatment, long-term follow-up is needed.

Background: Management of patients with total intestinal aganglionosis (TIA) is a medical challenge because of their dependency on parenteral nutrition (PN). Intestinal transplantation (ITx) represents the only alternative treatment for patients with irreversible intestinal failure for achieving intestinal autonomy., Methods: Among 66 patients who underwent ITx in our center, 12 had TIA. They received either isolated ITx (n = 4) or liver-ITx (LITx, n = 8) after 10 to 144 months of total PN. All grafts included the right colon., Results: After a median follow-up of 57 months, the survival rate was 62.5% in the LITx group and 100% in the ITx patients. The graft survival rate was 62.5% in the LITx group and 75% in the ITx group. All the surviving patients were fully weaned from total PN, after a median of 57 days. Pull through of the colon allograft was carried out in all patients. Fecal continence is normal in all but one of the surviving children., Conclusion: These results suggest that ITx with colon grafting should be the preferred therapeutic option in TIA. Early referral to a transplantation center after diagnosis of TIA is critical to prevent PN-related cirrhosis and thereby to permit ITx, which is associated with a good survival rate.

Objective: Small bowel (SB) transplantation (Tx), long considered a rescue therapy for patients with intestinal failure, is now a well recognised alternative treatment strategy to parental nutrition (PN). In this retrospective study, we analysed graft functions in 31 children after SBTx with a follow-up of 2-18 years (median 7 years)., Patients: Twelve children had isolated SBTx, 19 had combined liver-SBTx and 17 received an additional colon graft. Growth, nutritional markers, stool balance studies, endoscopy and graft histology were recorded every 2-3 years post-Tx., Results: All children were weaned from PN after Tx and 26 children remained PN-free. Enteral nutrition was required for 14/31 (45%) patients at 2 years post-Tx. All children had high dietary energy intakes. The degree of steatorrhoea was fairly constant, with fat and energy absorption rates of 84-89%. Growth parameters revealed at transplantation a mean height Z-score of -1.17. After Tx, two-thirds of children had normal growth, whereas in one-third, Z-scores remained lower than -2, concomitant to a delayed puberty. Adult height was normal in 5/6. Endoscopy and histology analyses were normal in asymptomatic patients. Chronic rejection occurred only in non-compliant patients. Five intestinal grafts were removed 2.5-8 years post-Tx for acute or chronic rejection., Conclusions: This series indicates that long-term intestinal autonomy for up to 18 years is possible in the majority of patients after SBTx. Subnormal energy absorption and moderate steatorrhoea were often compensated for by hyperphagia, allowing normal growth and attainment of adult height. Long-term compliance is an important pre-requisite for long-term graft function.

Intestinal epithelial cells and the mucosal immune cells in close proximity are thought to interact very closely. One well-established mechanism of this intercellular cross-talk is via the production of cytokines such as interferon gamma (IFNgamma). The aim of this study was to analyze the effects of IFNgamma on intestinal crypt epithelial cells. IEC-6 cells were cultured in the presence or absence of IFNgamma to measure its effects on proliferation, cell cycle, apoptosis, and major histocompatibility complex (MHC) class II antigen expression. Even at very low doses (0.01 U/ml), IFNgamma significantly inhibited IEC-6 cell proliferation, as demonstrated by reduced 3H-thymidine uptake, stable cell count, and complete arrest in the quiescent G0/G1 phase of the cell cycle. Incubation with supraphysiological doses of IFNgamma (100-1,000 U/ml) did not induce apoptosis, as assessed by morphology and the TUNEL assay. IFNgamma significantly induced de novo IEC-6 class II antigen expression. Tumor necrosis factor alpha (TNF alpha), which alone had no effect, synergistically enhanced this effect of IFNgamma. MHC class II antigen expression was observed to be independent of cell cycle phase. Our results indicate that IFNgamma alters immature crypt epithelial cell turnover and upregulates MHC class II expression. These alterations may be important in the pathogenesis of immune-mediated bowel disorders.

13C-labeled glycosyl ureides were recently proposed as a new marker of the orocecal transit time: after passing the small bowel the sugar-urea bond is split by bacterial allantoicase. Further degradation results in 13CO2 which can be measured in the exhaled breath. The aim of this study was to detect an eventual allantoicase-like activity in the human gut and to elucidate the metabolism of glycosyl ureides by human intestinal brush border enzymes. Biopsies of 15 duodenal specimen and 6 colon specimen were homogenised and incubated with several disaccharides and their corresponding disaccharide ureides under various experimental conditions. Hydrolysis of the sugar-urea bond could not be observed neither in the small bowel nor in the colon. However, the conjugation between the two sugars was split. In a modified Dahlqvist assay lactase showed the same kinetics with lactose and lactose ureide as substrates whereas maltose showed a significantly 2.6-fold higher affinity to maltase than maltose ureide (P < 0.001). No major difference between these two substrates could be detected when total maltase activity was inhibited by acarbose. In summary, the human gut tissue possesses no allantoicase-like activity. Therefore, glycosyl ureides seem to be appropriate substances to test the orocecal transit time.