Updating the Surgical Preference List.

Surgical procedure 'preference lists' are used worldwide, but their practice varies widely. Despite being positioned at a critical point in a surgical care pathway, they are often underemphasized, poorly maintained, and substandard. The following editorial material is gleaned from our experience in the set-up of a tertiary hospital on a green field site in Qatar. We comment on the use of preference lists, and contend that focus on standardizing and maintaining preference lists within an electronic record affords substantial opportunities for cost containment, whilst adding efficiency, safety, and value. We believe this approach represents an 'easy win' which would be applicable elsewhere.

The glucagon like peptide-2 'axis': Capacity for production and response following intestinal resection or repair of gastroschisis in infants.

PURPOSE: This study investigates the relationship between the enteric hormone glucagon-like peptide 2 (GLP-2) production, sensitivity, and intestinal adaptation in infants following resection or repair of gastroschisis. METHODS: With IRB approval (UCalgary #10656), consent was obtained from families of infants undergoing surgery for prospective monitoring of nutritional status, GLP-2 levels, and where possible, tissue sampling. RESULTS: Infants who adapted and weaned from parenteral nutrition (PN) had increased GLP-2 (86±32) n=24 vs. controls: 45±20 n=10 and vs. patients on prolonged PN: 42±6 pM, n=10). This was maintained to one year: weaned patients: 72±49 vs. non-weaned: 35±15 pM (p<0.05). Infants with gastroschisis (n=33) had decreased GLP-2 levels until enteral function was achieved and then became elevated: (21±15 with first feeding vs. 102±60 at full feeds and 60±19 pM at one year). There were no changes in the density or distribution of GLP-2 producing L-cells related to gestational age, nor in the expression of the GLP-2 receptor. CONCLUSION: GLP-2 levels correlate with intestinal adaptation in infants, and with recovery of intestinal function in gastroschisis. GLP-2 productive capacity (L-cell expression) and GLP-2 receptor expression do not vary with maturity. The findings support a role for GLP-2 in regulating intestinal function. Further study is suggested.

Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats.

OBJECTIVE: To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats. BACKGROUND: GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear. METHODS: Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition. RESULTS: Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss. CONCLUSIONS: Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study.

A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure.

BACKGROUND & AIMS: Glucagon-like peptide 2 (GLP-2) analogues are approved for adults with intestinal failure (IF), but no studies have included infants. This study examined the pharmacokinetics (PK), safety, and nutritional effects of GLP-2 in infants with IF. METHODS: With parental consent (Health Canada Protocol:150,979), parenteral nutrition (PN)-dependent infants were treated with 5-20-µg/kg/day GLP-2 for 3days (phase 1), and if tolerated continued for 42days (phase 2). Nutritional therapy was by primary caregivers, and follow-up was to one year. RESULTS: Six patients were enrolled, age 5.4±3.2months, bowel length: 27±12% of predicted, PN dependent (67±18% of calories). GLP-2 did not affect vital signs, nor were there significant adverse events during the trial. Dosing 5µg/kg/day gave GLP-2 levels of 52-57pmol/L, with no change in half-life or endogenous GLP-2 levels. Enteral feeds, weight, Z scores, stooling frequency, and citrulline levels improved numerically. The trial was discontinued early because of a drop in potency. CONCLUSIONS: GLP-2 was well tolerated in infants, and pK was similar to children with no changes in endogenous GLP-2 release. The findings suggest that GLP-2 ligands may be safely used in infants and may have beneficial effects on nutritional status. Further study is required. LEVEL OF EVIDENCE: 2b Prospective Interventional Study.

Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure.

BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure. METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year. RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in z scores and citrulline levels; the z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued. CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.

Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome [Formula: see text].

BACKGROUND: We aim to study the efficacy of exogenously administered glucagon-like peptide 2 (GLP-2) on intestinal adaptation in 2 preclinical models of neonatal short bowel syndrome (SBS) according to remnant intestinal anatomy, with and without ileum. Furthermore, we aim to determine if this adaptive effect was potentiated with enteral nutrition (EN). METHODS: Neonatal piglets were block-randomized to 75% mid-intestinal (JI group, retains ileum) or distal-intestinal (JC group, has no ileum) resection or no resection (sham control) and GLP-2 treatment (11 nmol/kg/d) or saline control for 7 days. Piglets received nutrition support, either 100% parenteral nutrition (PN; 0% EN, n = 32 in total) or 80% PN + 40% EN (n = 28 in total). Adaptation was assessed by morphological and histological changes, as well as RT quantitative polymerase chain reaction of nutrient transporters and tight junctional proteins and fat absorption. Data are analyzed by 3-way analysis of variance (ANOVA) and 2-way ANOVA per EN level. RESULTS: GLP-2 treatment lengthened villi, deepened crypts, and improved intestinal weight in the remnant intestine of JC piglets. EN was a more potent adaptive stimulus for JI piglets. Small intestinal lengthening occurred only in the JI group, when given EN. There was no difference in total fat absorption and messenger RNA expression of nutrient transporters and tight junctional proteins. CONCLUSIONS: GLP-2 administration augmented structural adaptation in JC piglets with distal intestinal resection. Given JI anatomy, further stimulation by GLP-2 treatment over innate adaptation and stimulation by EN was modest and restricted to ileum. The differential effect of GLP-2 in neonatal SBS, depending on remnant anatomy, has important implications for clinical translation and planning of clinical trials.

Pathophysiology, prevention, treatment, and outcomes of intestinal failure-associated liver disease.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) remains a serious problem in the treatment of infants with nutritional problems and short bowel syndrome. METHODS: A review of the recent literature from 2010 to 2016, concentrating on articles related to the pathophysiology of IFALD and to outcomes of novel nutritional and pharmacological therapies for neonatal cholestasis in the post-surgical neonate. RESULTS: The pathophysiology of IFALD relates to an increase sensitivity of the neonatal liver to cholestasis in the non-fed state; prolonged cholestasis almost inevitably results in liver damage which will progress from fibrosis to cirrhosis. Clinically discerned risk factors include premature birth, inflammation, sepsis, disruption of the enterohepatic circulation by creation of a proximal stoma, and the duration and type of parenteral nutritional support. Within the hepatocyte, the regulatory enzyme farsanoid receptor X (FXR) appears to play a pivotal role in the development of cholestasis. Recent studies have shown that its activity is suppressed by sepsis, and by plant phytosterols found in soy-based lipid preparations. This paradigm is reflected in the emerging consensus for the care of post-surgical neonates, which is based around a multi-disciplinary team approach. Using an algorithm-driven approach, an appropriate balance between caloric support and prevention of IFALD can be achieved. CONCLUSIONS: Further prospective studies are required to further refine the optimal sequence of use of these therapies and the long-term effects on neurological development and hepatic function. However, with optimal care, the number of IF patients progressing to end-stage liver disease because of IFALD should be very low.

Robotic-assisted minimally invasive surgery of the spine (RAMISS): a proof-of-concept study using carbon dioxide insufflation for multilevel posterior vertebral exposure via a sub-paraspinal muscle working space.

BACKGROUND: Open posterior spinal procedures involve extensive soft tissue disruption, increased hospital length of stay, and disfiguring scars. Our aim was to demonstrate the feasibility of using robotic-assistance for minimally invasive exposure of the posterolateral spine with and without carbon dioxide (CO2 ) insufflation. METHODS: Sheep specimens underwent minimally invasive subperiosteal dissection of the spine during three trials. The da Vinci S Surgical system was used for access with and without working space support via CO2 insufflation. RESULTS: Without insufflation, a sub-paraspinal muscle tunnel measuring 16 cm was developed between two 5 cm incisions. With insufflation, the one-sided tunnel length was 12.5 cm but without the soft tissue trauma and obstructed visualization experienced without CO2 . CONCLUSIONS: The use of robot-assistance for minimally invasive access to the posterior spine appears to be feasible. The use of CO2 insufflation greatly improved our ability to visualize and access the posterior vertebral elements.

Glucagon-Like Peptide 2 Improves Cholestasis in Parenteral Nutrition--Associated Liver Disease.

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) remains a significant cause of morbidity and mortality in neonates with intestinal failure. Although glucagon-like peptide-2 (GLP-2) is being advanced as therapy, the effect of GLP-2 treatment on PNALD is unknown. We aim to investigate the effect of exogenous GLP-2 administration on hepatic function in a neonatal piglet model of PNALD. METHODS: Neonatal piglets (aged 2-6 days) underwent jugular venous catheterization to receive isonitrogenous, isocaloric parenteral nutrition (PN). Piglets were allocated to 2 groups: group 1 (n = 8) received saline while group 2 (n = 7) received GLP-2 (at 11 nmol/kg/d). After 17 days, piglets underwent terminal laparotomy, and bile flow was measured. Liver specimens were analyzed histologically and with immunoperoxidase staining. Age-matched sow-reared control piglets (group 3, n = 8) were used for comparison. RESULTS: Both groups 1 and 2 receiving PN developed cholestasis relative to sow-reared controls, as evidenced by a decrease in bile flow and increase in serum total bilirubin. However, group 2 had improved bile flow (1.35 vs 0.73 µL/g; P = .02) and diminished bilirubin (38.0 vs 78.5 µmol/L; P = .008) compared with group 1. Group 2 also had lower serum alanine aminotransferase levels, a marker of liver injury. Histologically, the liver specimens in group 1 had marked hepatocyte pigmentation, which was decreased in group 2 specimens. CONCLUSIONS: The exogenous administration of GLP-2 is associated with the improvement of cholestasis and liver injury. This study introduces a novel role for GLP-2 in improving PNALD in the setting of prolonged PN duration.

Glucagon-Like Peptide-2 Alters Bile Acid Metabolism in Parenteral Nutrition--Associated Liver Disease.

BACKGROUND: We aim to study the mechanisms underlying our previous finding that exogenous glucagon-like peptide-2 (GLP-2) treatment in a preclinical model of neonatal parenteral nutrition-associated liver disease (PNALD) improves cholestasis. METHODS: Neonatal piglets received 17 days of parenteral nutrition (PN) therapy and either saline control (PN/Saline n = 8) or GLP-2 treatment at 11 nmol/kg/d (PN/GLP-2, n = 7). At terminal laparotomy, bile and liver samples were collected. The relative gene expression of enzymes involved in bile acid synthesis, regulation, and transport was measured in liver by reverse-transcriptase quantitative polymerase chain reaction. Bile acid composition in bile was determined using tandem mass spectrometry. Data were analyzed using 1-way analysis of variance (ANOVA) or Kruskal-Wallis ANOVA. RESULTS: GLP-2 increased the expression of bile acid export genes: multidrug resistance-associated proteins 2 (MRP2) (P = .002) and 3 (MRP3) (P = .037) over saline control. GLP-2 increased expression of Farnesoid X receptor (FXR) (P < .001) and CYP7A1 (cytochrome P450, family 7, subfamily A, polypeptide 1) (P = .03). GLP-2 treatment was associated with decreased concentrations of taurohyocholic acid and conjugates of toxic lithocholic acid (P < .01). GLP-2 treatment increased the liver bile acid content. CONCLUSIONS: GLP-2 treatment was associated with alterations in the hepatic expression of genes involved in bile acid metabolism. The transcriptomic results indicate the mechanisms at the transcriptional level acting to regulate bile acid synthesis and increase bile acid export. Differences in bile acid profiles further support a beneficial role for GLP-2 therapy in PNALD.

Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome: translational relevance and challenges.

Intestinal failure (IF), due to short bowel syndrome (SBS), results from surgical resection of a major portion of the intestine, leading to reduced nutrient absorption and need for parenteral nutrition (PN). The incidence is highest in infants and relates to preterm birth, necrotizing enterocolitis, atresia, gastroschisis, volvulus, and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, and nutritional and pharmacological interventions. Animal studies are needed to carefully evaluate the cellular mechanisms, safety, and translational relevance of new procedures. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult). Clinically relevant therapies have recently been suggested from studies in preterm and term PN-dependent SBS piglets, with or without a functional colon. Studies in rats and mice have specifically addressed the fundamental physiological processes underlying adaptation at the cellular level, such as regulation of mucosal proliferation, apoptosis, transport, and digestive enzyme expression, and easily allow exogenous or genetic manipulation of growth factors and their receptors (e.g., glucagon-like peptide 2, growth hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g., PN, milk diets, long-/short-chain lipids, pre- and probiotics). Conversely, newborn pigs (preterm or term) and weanling rats provide better insights into the developmental aspects of treatment for SBS in infants owing to their immature intestines. The review shows that a balance among practical, economical, experimental, and ethical constraints will determine the choice of SBS model for each clinical or basic research question.

Exogenous glucagon-like peptide-2 improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model of short bowel syndrome.

BACKGROUND: Endogenous glucagon-like peptide-2 (GLP-2) levels and intestinal adaptation are reduced in distal-intestinal resection animal models of short bowel syndrome (SBS) that lack remnant ileum. We hypothesized that exogenous GLP-2 would improve intestinal adaptation in a distal-intestinal resection neonatal piglet model of SBS. METHODS: In all, 35 piglets were randomized to 2 treatment and 3 surgical groups: control (sham), 75% mid-intestinal resection (JI), and 75% distal-intestinal resection (JC). Parenteral nutrition (PN) commenced on day 1 and was weaned as enteral nutrition (EN) advanced. IV GLP-2 (11 nmol/kg/d) or saline was initiated on day 2. Piglets were maintained for 14 d. Clinical, functional, morphological, and histological outcomes were obtained. RESULTS: JC-GLP-2 piglets had fewer days on PN (10.0 ± 0.6 vs. 13.8 ± 0.2), more days on EN (4.0 ± 0.6 vs. 0.2 ± 0.2), a higher percentage of EN at termination (92 ± 5 vs. 52 ± 10%), fewer days of diarrhea (8.0 ± 0.7 vs. 12.3 ± 0.4), increased intestinal length (19 ± 4 vs. -5 ± 3%), and deeper jejunal crypts (248 ± 21 vs. 172 ± 12 µm), compared with saline piglets. CONCLUSION: GLP-2 therapy improves clinical, morphological, and histological outcomes of intestinal adaptation in a distal-intestinal resection model of SBS. Since this anatomical subtype represents the majority of clinical cases of neonatal SBS, these results support a potential role for GLP-2 therapy in pediatric SBS.

Rising post-colectomy complications in children with ulcerative colitis despite stable colectomy rates in United States.

BACKGROUND AND AIMS: In children with ulcerative colitis, data on temporal colectomy trends and in-hospital post-colectomy complications are limited. Thus, we evaluated time trends in colectomy rates and post-colectomy complications in children with ulcerative colitis. METHODS: We identified all children (≤18years) with a diagnosis code of ulcerative colitis (ICD-9: 556.X) and a procedure code of colectomy (ICD-9: 45.8 and 45.7) in the Kids' Inpatient Database for 1997, 2000, 2003, 2006 and 2009. The incidence of colectomies for pediatric ulcerative colitis was calculated and Poisson regression analysis was performed to evaluate the change in colectomy rates. In-hospital postoperative complication rates were assessed and predictors for postoperative complications were evaluated using multivariate logistic regression. RESULTS: The annual colectomy rate in pediatric ulcerative colitis was 0.43 per 100,000person-years, which was stable throughout the study period (P>.05). Postoperative complications were experienced in 25%, with gastrointestinal (13%) and infectious (9.3%) being the most common. Postoperative complication rates increased significantly by an annual rate of 1.1% from 1997 to 2009 (P=.01). However, other independent predictors of postoperative complications were not identified. Patients with postoperative complications had significantly longer median length of stay (14.3days vs 8.2days; P<.001) and higher median hospital charges per patient (US $81,567 vs US $55,461; P<.001) compared to those without complications. CONCLUSION: Colectomy rates across the United States in children with ulcerative colitis have remained stable between 1997 and 2009; however, in-hospital postoperative complication rates have increased.

Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs.

BACKGROUND: The enteroendocrine hormone glucagon like peptide-2 (GLP-2) and its ligands are under development as therapeutic agents for a variety of intestinal pathologies. A number of these conditions occur in neonates and infants, and thus a detailed understanding of the effects of GLP-2 during the phase of rapid growth during infancy is required to guide the development of therapeutic applications. We studied the effects of GLP-2 in the neonatal pig to determine the potential effects of exogenous administration. METHODS: Two day old newborn domestic piglets were treated with GLP-2 (1-33) at 40 µg/kg/day or control drug vehicle (saline), by subcutaneous injection, given in two doses per day, (n=6/group) for 42 days. Animals were weaned normally, over days 21-25. In the fifth week of life, they underwent neuro-developmental testing, and a pharmacokinetic study. On day 42, they were euthanized, and a complete necropsy performed, with histological assessment of tissues from all major organs. RESULTS: GLP-2 treatment was well tolerated, one control animal died from unrelated causes. There were no effects of GLP-2 on weight gain, feed intake, or behavior. In the treated animals, GLP-2 levels were significantly elevated at 2400±600 pM while at necropsy, organ weights and histology were not affected except in the intestine, where the villus height in the small intestine and the crypt depth, throughout the small intestine and colon, were increased. Similarly, the rate of crypt cell proliferation (Ki-67 staining) was increased in the GLP-2 treated animals and the rate of apoptosis (Caspase-3) was decreased, the depth of the microvilli was increased and the expression of the mRNA for the GLP-2 receptor was decreased throughout the small and large intestine. CONCLUSIONS: In these growing animals, exogenous GLP-2 at pharmacologic doses was well tolerated, with effects confined to the gastrointestinal tract.

Effects of polymeric formula vs elemental formula in neonatal piglets with short bowel syndrome.

BACKGROUND: Intestinal adaptation is important for recovery in short bowel syndrome (SBS). This process is dependent on the presence of enteral nutrition (EN) and trophic factors, such as glucagon-like peptide-2 (GLP-2). In clinical practice, elemental formula is often used to feed neonates with SBS, whereas animal studies suggest polymeric formula promotes better intestinal adaptation. In neonatal piglet models of SBS, with or without ileum, we compared the elemental with the polymeric formula, including the effect on endogenous GLP-2. MATERIALS AND METHODS: Forty-eight piglets underwent 75% mid-intestinal resection with jejunoileal anastomosis, 75% distal-intestinal resection with jejunocolic anastomosis (JC), or sham without resection. Parenteral nutrition (PN) started postoperatively, tapering as EN was increased, according to clinical criteria, based on diarrhea and weight. Within groups, piglets were randomized to an isocaloric/isonitrogenous elemental (amino acid) or polymeric (intact protein) diet. Plasma GLP-2 and histology for adaptation were measured at 14 days. RESULTS: Within both SBS and control groups, no difference in adaptation was observed according to diet. A difference was observed only within the JC piglet group with regard to clinical outcomes. In these piglets, compared with elemental formula, the polymeric formula was associated with more diarrhea ( P = .023) and longer duration of PN support (P = .047). CONCLUSION: An overall benefit of the polymeric formula over the elemental formula on gut adaptation was not observed. Furthermore, SBS piglets without ileum had less ability to tolerate polymeric formula, contributing to more days of PN support.

From diarrhea to obesity in prohormone convertase 1/3 deficiency: age-dependent clinical, pathologic, and enteroendocrine characteristics.

GOALS: The aim of this report is to delineate the clinical, pathologic, and enteroendocrine (EE) features of prohormone convertase 1/3 (PC1/3) deficiency in children. BACKGROUND: Prohormone convertases play a pivotal role in the activation of biologically inactive hormones. Congenital defects in the EE axis, such as PC1/3 deficiency, have been rarely reported and their pathophysiological mechanisms are largely unknown. STUDY: EE function and pathology was evaluated in 4 males (1, 2, 7, and 10 y old) from 2 families with PC1/3 deficiency at a university children's hospital. Clinical course, pathology analysis including immunohistochemistry for PC1/3, PC2, and glucagon-like peptide 1 (GLP-1) and electron microscopy, as well as EE function tests (GLP-1, GLP-2, oral glucose tolerance test) were performed. RESULTS: All (n=4) suffered from congenital severe diarrhea associated with malabsorption. The diarrhea improved during the first year of life and hyperphagia with excessive weight gain (BMI>97th percentile) became the predominant phenotype at an older age. Analysis of the enteroendocrine axis revealed high proinsulin levels (57 to 1116 pmol/L) in all patients, low serum GLP-2 levels, and impaired insulin and GLP-1 secretion after an oral glucose tolerance test at a young age, with improvement in 1 older child tested. Electron microscopy showed normal ultrastructure of enterocytes and EE cells. Immunohistochemistry revealed normal expression of chromogranin A, a marker of EE cells but markedly reduced immunostaining for PC1/3 and PC2 in all patients. CONCLUSIONS: PC1/3 deficiency is associated with an age dependent, variable clinical phenotype caused by severe abnormalities in intestinal and EE functions. Serum level of proinsulin can be used as an effective screening tool.

A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients.

UNLABELLED: BACKGROUND/ OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release is triggered by nutrient contact. The authors hypothesized that ileal Crohn disease (CD) affects GLP-2 release. METHODS: With ethics board approval, pediatric patients hospitalized with CD were studied; controls were recruited from local schools. Inclusion criteria were endoscopy-confirmed CD (primarily of the small intestine) with a disease activity index >150. Fasting and postprandial GLP-2 levels and quantitative urinary recovery of orally administered 3-O-methyl-glucose (active transport) and lactulose/mannitol (passive) were quantified during the acute and remission phases. RESULTS: Seven patients (mean [± SD] age 15.3 ± 1.3 years) and 10 controls (10.3 ± 1.6 years) were studied. In patients with active disease, fasting levels of GLP-2 remained stable but postprandial levels were reduced. Patients with active disease exhibited reduced glucose absorption and increased lactulose/mannitol recovery; all normalized with disease remission. The change in the lactulose/mannitol ratio was due to both reduced lactulose and increased mannitol absorption. CONCLUSIONS: These findings suggest that pediatric patients with acute ileal CD have decreased postprandial GLP-2 release, reduced glucose absorption and increased intestinal permeability. Healing of CD resulted in normalization of postprandial GLP-2 release and mucosal functioning (nutrient absorption and permeability), the latter due to an increase in mucosal surface area. These findings have implications for the use of GLP-2 and feeding strategies as a therapy in CD patients; further studies of the effects of inflammation and the GLP-2 axis are recommended.

Early feeding in pediatric patients following stoma closure in a resource limited environment.

BACKGROUND: Establishment of enteral nutrition is necessary after intestinal surgery. In resource-strained environments, it can be critical. This study examined the effect of early feeding in pediatric patients undergoing stoma closure in a country with mid-level socioeconomic indices. METHODS: With parenteral consent and ethics board approval, patients were prospectively enrolled in early feeding (Group 1), starting feeds 24h post-operation with a protocol driven increase. They were compared with similar patients managed without a specific protocol over the 12 months prior (Group 2). RESULTS: There were 31 patients in each group with similar mean age and weight. The mean first sustained feed was achieved at 28.5 ± 4.4 h* in Group 1 vs. 153.8 ± 28.6 h in Group 2. Full feeds were achieved within 62.3 ± 19.2 h* vs. 196.0 ± 40.5 h in Group 1 and 2, respectively. Mean hospital stay was 7.2 days* in Group 1 vs. 9.4 days in Group 2. A reduction in postoperative fever and wound infections was observed in Group 1 (*p<0.05). CONCLUSION: Early enteral feeding after elective bowel anastomosis is well tolerated in children and results in shorter hospital stay and fewer complications.

Longer term effects of closed repair of pectus excavatum on cardiopulmonary status.

BACKGROUND: The "Nuss" repair is done for correction of moderate to severe pectus excavatum (PE). The long term cardiopulmonary and psychosocial effects of repair are uncertain. The objective of this study was to compare cardiopulmonary function and subjective evaluation of appearance and exercise tolerance pre-bar insertion with post-bar removal. METHODS: All patients underwent preoperative and post-bar (3 month) removal evaluation with complete pulmonary function tests, exercise stress testing, echocardiogram, and self-rated appearance and exercise tolerance scoring. The protocol was approved by the regional ethics board, and all families gave informed consent. RESULTS: Sixty-seven patients underwent pre and post testing. Preoperative CT index was 4.4 ± 1.3. Cardiopulmonary outcomes, standardized for height and weight, showed significant improvements in FEV-1 as (pre) 81.1 ± 17.0 vs post 89.8 ± 20.5*, FVC: 91.2 ± 18.6 vs 98.9 ± 22.9*, O2 pulse: 75.8 ± 14.4 vs 80.5 ± 18.3* (each as % predicted). Both the self-ratings of appearance (2.5 ± 0.8 vs 4.4 ± 0.5) and ability to exercise (3.3 ± 0.7 vs 4.3 ± 0.6, scale 1-5) increased significantly. (All data: mean ± St Dev, *p<0.05) CONCLUSIONS: Closed repair of PE results in improvements in pulmonary and aerobic exercise function and perceived appearance and exercise tolerance. Our data suggest that the impact on appearance and self-perceived well being is greater than the physical effect.