Search

Background and Aim: There have been no large-scale epidemiological study of functional constipation of pediatric gastroenterology services. This survey was undertaken to investigate the prevalence of functional constipation and magnitude of related problems in hospital settings of various countries as well as the practice of pediatric gastroenterologists in management of these conditions. Methods: The survey was conducted by sending questionnaires to members of Societies for Pediatric Gastroenterology Hepatology and Nutrition of various continents. Results: A total of 274 pediatric gastroenterologists from 41 countries participated in this study. Functional constipation accounted for overall 30% of patients attending pediatric gastroenterology outpatient clinics. In comparison with non-western countries, respondents from western countries reported significantly higher median annual numbers of new patients with intractable functional constipation (10 [4,25] vs 5 [2,10], P < 0.001), dyssynergic defecation (3 [0,15] vs 1 [0,4], P < 0.001), and colonic inertia (2 [0,5] vs 0 [0,1], P < 0.001). The use of high dose polyethylene glycol for fecal disimpaction was significantly more commonly among respondents from western countries, whereas rectal enema was significantly more favored in non-western countries. Respondents from different continents reported significant discrepancies in choices of investigations and management of patients with dyssynergic defecation and colonic inertia. Conclusions: Functional constipation is a major problem for pediatric gastroenterology outpatient services worldwide. There were significant variations in the investigations of choice and therapeutic management of functional constipation, intractable functional constipation, and related problems among pediatric gastroenterologists of different geographic regions.

COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission., Several clinical reports have described gastrointestinal symptoms for COVID-19, though whether the virus can replicate within the stomach remains unclear. Here the authors generate gastric organoids from human biopsies and show that the virus can efficiently infect gastric epithelium, suggesting that the stomach might have an active role in fecal-oral transmission.

Background The main aim of the study was to assess the association between joint hypermobility (JH) and gastrointestinal (GI) disorders in children. Methods All children aged 4-17 years attending the clinics of the participating Pediatric Gastroenterology Centres for functional GI disorders (FGIDs) and inflammatory bowel disease (IBD) were screened for joint laxity. JH diagnosis was inferred using the Beighton Score. JHS diagnosis was inferred based on the Brighton Criteria. Rome III Diagnostic Criteria were used to diagnose possible FGIDs. Ulcerative colitis and Crohn`s disease diagnoses were made according to the Porto Criteria. Age and sex- matched healthy children were enrolled as controls. Results One-hundred-seventy children with GI disorders (70 with FGIDs, 50 with Crohn`s disease, and 50 with ulcerative colitis) and 100 healthy controls were enrolled in the study. JH was reported in 7/70 (10%) children with FGIDs (p=0.26 compared to controls), 4/50 (8%) children with Crohn`s disease (p=0.21 compared to controls) and 15/50 (30%) children with ulcerative colitis (p=0.09 compared to controls; p=0.01 compared to FGIDs; p=0.01 compared to Crohn`s). Conclusions JH is more prevalent in patients suffering from ulcerative colitis compared to the healthy general population, yet the difference did not reach statistical significance. Likely, a proportion of children with ulcerative colitis and JH may show connective tissue abnormalities. However, whether JH can be considered a possible feature of pediatric GI disorders deserves further investigation.

Exclusive breastfeeding ideally up to 6 months of life is the feed of choice for infants and should be promoted by healthcare professionals. However, when human milk is not sufficient or not available, infant formula, generally cow's milk-based, meeting strictly regulated nutritional and safety requirements, are recommended. Human breastmilk feeding has a positive health impact for both mother and child, but there is limited evidence that it has a long-term protective effect on the development of allergic disease. Some studies have found an association of an increased risk to develop cow's milk allergy with early exposure to cow's milk protein in formula milk. As a result, over the last 30 years, partially hydrolyzed formulas (pHF) have gained popularity and, more recently, become embroiled in a debate about their role in the primary prevention of allergic outcomes. Similar debates exist in regards to the potential preventative effects of pre-, pro- and synbiotics as well as nutritional factors, notably vitamin D and omega-3 fatty acids. This paper aims to critically address these aspects, drawing information from published data interpreted by an international expert group in paediatrics, allergy, gastro-intestinal diseases and nutrition. This group of experts emphasize that human milk is the optimal source of infant nutrition. With regards to pHFs, whilst no harm has been shown with their use and some studies have suggested potential benefit preventing atopic dermatitis in at risk infants, there is insufficient evidence for or against their routine recommendation for primary allergy prevention. The method of hydrolysation differs for every formula. There is insufficient evidence to recommend supplementation with vitamin D, omega-3 LCPUFA, specific prebiotic oligosaccharides or specific probiotic strains during pregnancy, lactation and early life to prevent the development of allergic disease in children. There remains a need for well-designed trials with the currently commercialised pHFs and supplements to allow for better clarity and evidence-based recommendations.

Paediatric functional abdominal pain disorders, currently referred to as disorders of gut-brain interaction, comprise irritable bowel syndrome, functional dyspepsia, abdominal migraine and functional abdominal pain not otherwise specified, as defined by the Rome IV diagnostic criteria. Functional abdominal pain disorders are common disorders with a prevalence of 3-16% depending on country, age and sex. A greater understanding of aetiopathogenesis and pathophysiology is emerging and includes intestinal components (inflammation, motility and the microbiota), central factors (psychological aspects, sensitization and/or differences in connectivity or activity of certain brain regions) as well as extrinsic factors (infections). In particular, the timing of disruption of the microbiota-gut-brain axis seems to be important. Diagnosis is challenging but is primarily based on clinical symptoms and exclusion of other organic causes, with an emphasis on avoiding unnecessary invasive diagnostic procedures. The available pharmacological interventions are limited in children and, therefore, management has focused on combined approaches, including mind-targeted interventions (hypnotherapy and cognitive behavioural therapy), diet (probiotics) and percutaneous electrical nerve field stimulation. The evidence for their clinical efficacy, although limited, is favourable, with positive impacts on symptoms and overall quality of life. The coming decades hold promise for improved understanding and management of these enigmatic disorders.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global public health emergency. COVID-19 typically manifests as a respiratory illness but an increasing number of clinical reports describe gastrointestinal (GI) symptoms. This is particularly true in children in whom GI symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. By contrast, fetuses seem to be rarely affected by COVID-19, although the virus has been detected in placentas of affected women. These observations raise the question of whether the virus can infect and replicate within the stomach once ingested. Moreover, it is not yet clear whether active replication of SARS-CoV-2 is possible in the stomach of children or in fetuses at different developmental stages. Here we show the novel derivation of fetal gastric organoids from 8-21 post-conception week (PCW) fetuses, and from pediatric biopsies, to be used as an in vitro model for SARS-CoV-2 gastric infection. Gastric organoids recapitulate human stomach with linear increase of gastric mucin 5AC along developmental stages, and expression of gastric markers pepsinogen, somatostatin, gastrin and chromogranin A. In order to investigate SARS-CoV-2 infection with minimal perturbation and under steady-state conditions, we induced a reversed polarity in the gastric organoids (RP-GOs) in suspension. In this condition of exposed apical polarity, the virus can easily access viral receptor angiotensin-converting enzyme 2 (ACE2). The pediatric RP-GOs are fully susceptible to infection with SARS-CoV-2, where viral nucleoprotein is expressed in cells undergoing programmed cell death, while the efficiency of infection is significantly lower in fetal organoids. The RP-GOs derived from pediatric patients show sustained robust viral replication of SARS-CoV-2, compared with organoids derived from fetal stomachs. Transcriptomic analysis shows a moderate innate antiviral response and the lack of differentially expressed genes belonging to the interferon family. Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. However, the virus can efficiently infect gastric epithelium in pediatric patients, suggesting that the stomach might have an active role in fecal-oral transmission of SARS-CoV-2.

Background: Colonic manometry with intraluminal bisacodyl infusion can be used to assess colonic neuromuscular function in children with treatment-refractory constipation. If bisacodyl does not induce high-amplitude propagating contractions (HAPCs), this can be an indication for surgical intervention. A detailed characterization of the colonic response to intraluminal bisacodyl in children with constipation may help to inform clinical interpretation of colonic manometry studies. Methods: Studies were performed in five pediatric hospitals. Analysis included identification of HAPCs, reporting HAPCs characteristics, and an area under the curve (AUC) analysis. Comparisons were performed between hospitals, catheter type, placement techniques, and site of bisacodyl infusion. Results: One hundred and sixty-five children were included (median age 10, range 1-17 years; n = 96 girls). One thousand eight hundred and ninety-three HAPCs were identified in 154 children (12.3 ± 8.8 HAPCs per child, 0.32 ± 0.21 HAPCs per min; amplitude 113.6 ± 31.5 mm Hg; velocity 8.6 ± 3.8 mm/s, propagation length 368 ± 175 mm). The mean time to first HAPC following bisacodyl was 553 ± 669 s. Prior to the first HAPC, there was no change in AUC when comparing pre- vs post-bisacodyl (Z = −0.53, P =.60). The majority of HAPCs terminated in a synchronous pressurization in the rectosigmoid. Defecation was associated with HAPCs (χ 2(1)=7.04, P

Background Hirschsprung’s disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. Aims This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. Methods Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. Results Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. Conclusion In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.

Motility of the gastrointestinal tract plays a critical role in the maintenance of its many physiological functions. These motility patterns, which vary along the gastrointestinal tract, are achieved by highly coordinated interactions between the neuromusculature of the gut (smooth muscle layers, enteric nervous system, interstitial cells of Cajal), central nervous system, autonomic nervous system, hormones, peptides and the microbiome. Other external factors such as diet, and age related changes in the gastrointestinal tract also, ultimately, affect gastrointestinal motility. A subtle change in any of the above factors could significantly impact on gastrointestinal function leading to pediatric gastrointestinal motility disorders. Here, we review common motility disorders in children and provide an indepth understanding of the pathophysiology and management of these problem.

Background and AimsInflammatory bowel disease [IBD] is often one of the most devastating and debilitating chronic gastrointestinal disorders in children and adolescents. The main objectives here were to systematically review the incidence and prevalence of paediatric IBD across all 51 European states.MethodsWe undertook a systematic review and meta-analysis based on PubMed, CINAHL, the Cochrane Library, searches of reference lists, grey literature and websites, covering the period from 1970 to 2018.ResultsIncidence rates for both paediatric Crohn’s disease [CD] and ulcerative colitis [UC] were higher in northern Europe than in other European regions. There have been large increases in the incidence of both paediatric CD and UC over the last 50 years, which appear widespread across Europe. The largest increases for CD have been reported from Sweden, Wales, England, the Czech Republic, Denmark and Hungary, and for UC from the Czech Republic, Ireland, Sweden and Hungary. Incidence rates for paediatric CD have increased up to 9 or 10 per 100 000 population in parts of Europe, including Scandinavia, while rates for paediatric UC are often slightly lower than for CD. Prevalence reported for CD ranged from 8.2 per 100 000 to approximately 60 and, for UC, from 8.3 to approximately 30.ConclusionsThe incidence of paediatric IBD continues to increase throughout Europe. There is stronger evidence of a north–south than an east–west gradient in incidence across Europe. Further prospective studies are needed, preferably multinational and based on IBD registries, using standardized definitions, methodology and timescales.

Objectives The main aim of this study was to determine the impact on clinical practice of the first European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper on the diagnosis and management of nutritional and gastrointestinal problems in children with neurological impairment (NI). Methods In this pilot-study, a web-based questionnaire was distributed between November, 2019 and June, 2020, amongst ESPGHAN members using the ESPGHAN newsletter. Fifteen questions covered the most relevant aspects on nutritional management and gastrointestinal issues of children with NI. A descriptive analysis of responses was performed. Results A total of 150 health professionals from 23 countries responded to the survey. A considerable variation in clinical practice concerning many aspects of nutritional and gastrointestinal management of children with NI was observed. The most frequently used method for diagnosing oropharyngeal dysfunction was the direct observation of meals with or without the use of standardised scores (n = 103). Anthropometric measurements were the most commonly used tools for assessing nutritional status (n = 111). The best treatment for gastroesophageal reflux disease (GERD) was considered to be proton pump inhibitor therapy by most (n = 116) participants. Regarding tube feeding, nearly all respondents (n = 114) agreed that gastrostomy is the best enteral access to be used for long-term enteral feeding. Fundoplication was indicated at the time of gastrostomy placement especially in case of uncontrolled GERD. Conclusions More studies are required to address open questions on adequate management of children with NI. Identifying knowledge gaps paves the way for developing updated recommendations and improving patient care.

The gut-brain axis has recently emerged as a key modulator of human health and the intestinal microbiome has a well-recognised pivotal role in this strong connection. The aim of this narrative review is to update and summarise the effect and clinical applicability of probiotics in paediatric neurogastroenterology. The Cochrane Database and PubMed were searched using keywords relating to different subtypes of functional gastrointestinal disorders (FGIDs) and their symptoms, those relating to the CNS and related neurological or behavioural dysfunction as well as 'probiotic' OR 'probiotics'. Included papers were limited to those including children (aged 0-18 years) and using English language. Although significant effects of specific strains have been reported in infants with FGIDs, heterogeneity amongst the studies (different products and concentrations used and FGID subtypes), has limited the ability to draw an overall conclusion on the clinical value of probiotics. According to different meta-analyses of randomised controlled trials, the use of Lactobacillus reuteri (DSM 17938) was associated with a significant decrease in average crying time in infantile colic. There is moderate evidence for this strain and LGG and limited evidence (based on one study each) for the beneficial effect of VSL#3 and a three-strain bifidobacteria mix in abdominal pain FGIDs, particularly in the irritable bowel disease subgroup of children, but not in functional dyspepsia. There is currently no clear evidence of positive effects of oral probiotics in autistic spectrum disorder. Efficacy and safety of other strains or beneficial effects in other conditions still need to be proven, as probiotic properties are strain-specific, and data cannot be extrapolated to other brain-gut or mood diseases or to other probiotics of the same or different species. To transform the use of probiotics from a tempting suggestion to a promising treatment modality in neurogastroenterological disorders more accurate differentiation of the efficacy-proven strains, clarification of dose, duration, and outcome and a careful selection of the target patients are still necessary. KEYWORDS: autism; behaviour; brain; functional gastrointestinal disorders; mood

The bewildering complexity of the enteric nervous system makes it susceptible to develop a wide array of motility disorders, collectively called enteric neuropathies. These gastrointestinal conditions are among the most challenging to manage, mainly given poor characterization of their etiopathophysiology and outcomes. Not surprisingly, therefore, targeted or curative therapies for enteric neuropathies are lacking and management is largely symptomatic. Nonetheless, recent advances in neurogastroenterology have witnessed improvements in established strategies, such as intestinal transplantation and the emergence of new treatments including novel drugs, electrical pacing, and manipulation of fecal microbiota, as well as stem cell and gene therapy.

Resumen: Los trastornos funcionales de dolor abdominal tienen una alta prevalencia en los niños. Estos trastornos pueden estar presentes por sí solos o en combinación con enfermedades orgánicas, tales como la enfermedad celíaca y las enfermedades inflamatorias intestinales. La inflamación intestinal (infecciosa y no infecciosa) predispone a los niños al desarrollo de hipersensibilidad visceral que puede manifestarse como trastornos funcionales de dolor abdominal, entre ellos el síndrome de intestino irritable. La aparición de síntomas de síndrome de intestino irritable en un paciente con una enfermedad orgánica subyacente, como la enfermedad inflamatoria intestinal, es un reto clínico, dado que la misma sintomatología puede representar un periodo de exacerbación de la enfermedad inflamatoria intestinal o un trastorno de dolor abdominal funcional sobrepuesto. Así mismo, puede ser que los síntomas del síndrome de intestino irritable en un niño con diagnóstico de enfermedad celíaca ocurran por un inadecuado control de la enfermedad celíaca o por la sobreposición con un trastorno de dolor abdominal funcional. Existe poca investigación acerca de la sobreposición de los trastornos funcionales abdominales y las enfermedades orgánicas en niños. Los estudios sugieren que la sobreposición entre los trastornos funcionales de dolor abdominal y la enfermedad inflamatoria intestinal es más común en adultos que en niños. Las causas de estas diferencias de prevalencia son aún desconocidas. Solo se han publicado unos cuantos estudios que tratan el tema de la sobreposición entre la enfermedad celíaca y los trastornos funcionales abdominales en niños. El presente artículo proporciona una revisión de la literatura acerca de la sobreposición entre la enfermedad celíaca, la enfermedad inflamatoria intestinal, y los trastornos funcionales de dolor abdominal en niños, además de establecer comparaciones con estudios realizados en adultos. Abstract: Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults. Palabras clave: Dolor abdominal, Enfermedad celíaca, Enfermedad inflamatoria intestinal, Niños, Inflamación gastrointestinal, Keywords: Abdominal pain, Celiac disease, Inflammatory bowel disease, Children, Gastrointestinal inflammation

Background The N-Myc Downstream-Regulated Gene (NDRG) family comprises four members that function in cellular processes like proliferation and differentiation. While NDRG1 and NDRG2 are extensively studied, knowledge regarding NDRG3 and NDRG4, despite its recognition as a well-established early-detection marker for colorectal cancer (Cologuard®), is sparse. Scope of review To summarize expression, biomarker potential and functional mechanisms of the NDRGs in the developing, mature and cancerous gut, we combine current literature and in silico analyses from the TCGA-database, GTEX Project, E14.5 mouse intestine and enteric neural crest cells, and an RNA-sequencing time-series of human embryonic colonic samples. Major conclusions This study reveals that all members display a differential expression pattern in the gut and that NDRG1, NDRG2 and NDRG4 (1) can serve as biomarker for colorectal cancer and (2) have tumor suppressive properties mainly affecting cell proliferation and epithelial-mesenchymal transition. General significance Similar effects of the NDRGs on the key-hallmarks of cancer, could implicate analogous functions in other tissue/cancer types.

Spinal cord injury (SCI) causes paralysis, multisystem impairment and reduced life expectancy, as yet with no cure. Stem cell therapy can potentially replace lost neurons, promote axonal regeneration and limit scar formation, but an optimal stem cell source has yet to be found. Enteric neural stem cells (ENSC) isolated from the enteric nervous system (ENS) of the gastrointestinal (GI) tract are an attractive source. Here, we used the chick embryo to assess the potential of ENSC to integrate within the developing spinal cord. In vitro, isolated ENSC formed extensive cell connections when co‐cultured with spinal cord (SC)‐derived cells. Further, qRT‐PCR analysis revealed the presence of TuJ1(+) neurons, S100(+) glia and Sox10(+) stem cells within ENSC neurospheres, as well as expression of key neuronal subtype genes, at levels comparable to SC tissue. Following ENSC transplantation to an ablated region of chick embryo SC, donor neurons were found up to 12 days later. These neurons formed bridging connections within the SC injury zone, aligned along the anterior/posterior axis, and were immunopositive for TuJ1. These data provide early proof of principle support for the use of ENSCs for SCI, and encourage further research into their potential for repair.

Background Combined pH-impedance monitoring has been suggested as the investigation of choice for diagnosing gastro-oesophageal reflux in children. Although it is superior to oesophageal pH monitoring in detecting all types of reflux episodes (acid, weakly acidic and alkaline) with the ability to evaluate symptom association with reflux events, it is still limited by the lack of true paediatric normal value and the high cost involved (equipment and personnel). Objective To produce a position statement on behalf of the Motility Working Group of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition on the indications and practical application of combined oesophageal pH-impedance monitoring in children. Methods Up-to-date review of available evidence. Results This document provides a practical guide to clinician on indications, methods and results interpretation of paediatric multichannel intraluminal impedance pH (MII-pH). Conclusions MII-pH is increasingly used by paediatricians as the diagnostic tool for assessing gastro-oesophageal reflux disease and symptom association. There is wide variation in paediatric practice and a need for standardised practice.

Intestinal failure (IF), following extensive anatomical or functional loss of small intestine (SI), has debilitating long-term effects on infants and children with this condition. Priority of care is to increase the child’s length of functional intestine, jejunum in particular, to improve nutritional independence. Here we report a robust protocol for reconstruction of autologous intestinal mucosal grafts using primary IF patient materials. Human jejunal intestinal organoids derived from paediatric IF patients can be expanded efficiently in vitro with region-specific markers preserved after long-term culture. Decellularized human intestinal matrix with intact ultrastructure is used as biological scaffolds. Proteomic and Raman spectroscopic analyses reveal highly analogous biochemical composition of decellularized human SI and colon matrix, implying that they can both be utilised as scaffolds for jejunal graft reconstruction. Indeed, seeding of primary human jejunal organoids to either SI or colonic scaffolds in vitro can efficiently reconstruct functional jejunal grafts with persistent disaccharidase activity as early as 4 days after seeding, which can further survive and mature after transplantation in vivo. Our findings pave the way towards regenerative medicine for IF patients.

SummaryThe enteric nervous system (ENS) is derived primarily from the vagal neural crest, a migratory multipotent cell population emerging from the dorsal neural tube between somites 1-7. Defects in the development and function of the ENS give rise to a range of disorders, termed enteric neuropathies and include conditions such as Hirschsprung’s disease. Little is known about the signalling that specifies early ENS progenitors. This has, thus far, limited progress in the generation of enteric neurons from human Pluripotent Stem Cells (hPSCs) that could provide a useful tool for disease modelling and regenerative medicine. We describe the efficient and accelerated generation of ENS progenitors from hPSCs, revealing that retinoic acid is critical for the acquisition of both vagal axial identity and early ENS progenitor specification. These ENS progenitors generate enteric neuronsin vitroand followingin vivotransplantation, achieving long-term colonisation of the ENS in adult mice. Thus, hPSC-derived ENS progenitors may provide the basis for cell therapy for defects in the ENS.

Background ‘Intractable constipation’ (IC) is constipation unresponsive to 3 months of optimal conventional treatment. Colonic manometry (CM) is recommended as a diagnostic modality for evaluation of these children. This study aimed to review outcomes of children with IC who were managed surgically at a single tertiary care center. Methods Records of children with IC who were treated with ACE (antegrade colonic enema), colostomy, or ileostomy (2006–2018) were reviewed. “Success” was defined as adequate evacuation without need for further unplanned surgery. Data are median (range). Results Sixty-seven children underwent surgery, of whom 56 with preoperative CM were included. Age at surgery was 8.6 (3.3–15.1) years. Eight had normal manometry and underwent ACE with 75% success. Thirty-six had left-sided dysfunction and underwent ACE (18), colostomy (14) or ileostomy (4) as initial intervention with 61, 70, and 100% success. Twelve with pancolonic dysfunction underwent ACE (6) or ileostomy (6) with 60 and 100% success. Twenty underwent repeat manometry 2.2 years (10 months–7.6 years) after surgery. Of 18 with stoma, 8 had resolution or improvement and of these, 7 underwent stoma reversal with a simultaneous ACE. Two patients with ACE had improvement, 1 is still on ACE washouts, and 1 is off all treatment. Ten with persistent dysfunction remain diverted. At 3.2 years (4 months–9.9 years) follow-up, 18 remain on ACE washouts, 9 have colostomy, 19 ileostomy, and 10 are off treatment and doing well. Conclusion We present a large series of patients who were surgically managed for IC. CM may guide therapy in these children. Type of study Retrospective comparative study Level of evidence Level III.

Intestinal failure, following extensive anatomical or functional loss of small intestine, has debilitating long-term consequences for children1. The priority of patient care is to increase the length of functional intestine, particularly the jejunum, to promote nutritional independence2. Here we construct autologous jejunal mucosal grafts using biomaterials from pediatric patients and show that patient-derived organoids can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, which forms biological scaffolds. Proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human small intestine and colon scaffolds, indicating that they can be used interchangeably as platforms for intestinal engineering. Indeed, seeding of jejunal organoids onto either type of scaffold reliably reconstructs grafts that exhibit several aspects of physiological jejunal function and that survive to form luminal structures after transplantation into the kidney capsule or subcutaneous pockets of mice for up to 2 weeks. Our findings provide proof-of-concept data for engineering patient-specific jejunal grafts for children with intestinal failure, ultimately aiding in the restoration of nutritional autonomy.

Defecatory disorders in children, including chronic constipation (CC) and fecal incontinence (FI), are common conditions worldwide and have a significant impact on children, their families, and the healthcare system. Anorectal manometry (ARM) and high-resolution anorectal manometry (HRAM) are relatively novel tools for the assessment of anal sphincter function and rectal sensation and have contributed significantly to improving the understanding of the anorectum as a functional unit. ARM has been recognized as the investigation of choice for adults with symptoms of defecation disorders, including fecal incontinence (FI), evacuation difficulties, and constipation. Although it is the gold standard tool in adults, it has yet to be formally accepted as a standardized diagnostic tool in the pediatric age, with limited knowledge regarding indications, protocol, and normal values. ARM/HRAM is slowly becoming recognized among pediatricians, but given that there are currently no agreed guidelines there is a risk that will lead to diversity in practice. The British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN)-Motility Working Group (MWG) therefore has taken the opportunity to provide guidance on the use of ARM/HRAM in children with CC and/or FI.

OBJECTIVE: In therapeutic trials for infant gastroesophageal reflux disease (GERD), ways to define GERD and measure and report study outcomes vary widely. The aim of this study was to develop a core outcome set (COS) for infant GERD. METHODS: The COS was developed using the Delphi technique, adhering to the Outcome Measures in Rheumatology Initiative 2.0 recommendations. Healthcare professionals (HCPs) (predominantly pediatric gastroenterologists and general pediatricians) and parents of infants (age 0-12 months) with GERD, listed up to 5 primary goals of therapy from their perspective and up to 5 persistent signs or symptoms that would signify inadequate treatment. Outcomes mentioned by >10% of participants were included in 2 shortlists. Next, HCPs and parents rated and prioritized outcomes on these shortlists. Outcomes with the highest rank formed the draft COS. The final COS was created after 2 consensus meetings between an expert panel and patient representatives. RESULTS: In total, 125 of 165 HCPs (76%) and 139 of 143 parents (97%) of infants with GERD completed the first phase. The second phase was completed by 83 of 139 HCPs (60%) and 127 of 142 different parents (89%). Outcomes of these phases were discussed during the consensus meetings and a 9-item COS was formed: "Adequate Growth," "Adequate Relief," "Adverse events,", "Crying," "Evidence of Esophagitis," "Feeding Difficulties," "Hematemesis," "No Escalation of Therapy," and "Sleep Problems." CONCLUSIONS: We developed a COS for infant GERD consisting of 9 items that should minimally be measured in future therapeutic trials to decrease study heterogeneity and ease comparability of results.

Enteric neuropathies, such as Hirschsprung disease (HSCR), comprise a number of severe diseases of the enteric nervous system (ENS) of the gastrointestinal (GI) tract with, as yet, no cures. The replacement of absent or diseased enteric neurons via stem cell transplantation directly into diseased gut represents a novel, curative therapy. This idea is supported by over two decades of preclinical research, carried out mainly in mice, demonstrating that neural crest-derived stem cells can be isolated from the gut, expanded in culture, and transplanted into gut in vivo where they migrate, proliferate, differentiate, and become functionally active. Here, we review some of the learnings from these studies, outlining the diseases potentially amenable to stem cell replacement therapy, the animals used to model disease, the different types of stem cells that could be used for therapy, the methodologies developed to prepare and deliver stem cells to the gut, and cell safety considerations. With the significant progress that has already been made by the field, the aim of developing a curative stem cell therapy for devastating diseases of the enteric nervous system is rapidly approaching reality.

Objectives: Jejunal tube feeding (JTF) is increasingly becoming the standard of care for children in whom gastric tube feeding is insufficient to achieve caloric needs. Given a lack of a systematic approach to the care of JTF in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimize its utility and safety. Methods: A group of members of the Gastroenterology and Nutrition Committees of the European Society of Paediatric Gastroenterology Hepatology and Nutrition and of invited experts in the field was formed in September 2016 to produce this clinical guide. Seventeen clinical questions treating indications and contraindications, investigations before placement, techniques of placement, suitable feeds and feeding regimen, weaning from JTF, complications, long-term care, and ethical considerations were addressed. A systematic literature search was performed from 1982 to November 2018 using PubMed, the MEDLINE, and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalized. In the absence of evidence from randomized controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 33 recommendations were voted on using the nominal voting technique. Conclusions: JTF is a safe and effective means of enteral feeding when gastric feeding is insufficient to meet caloric needs or is not possible. The decision to place a jejunal tube has to be made by close cooperation of a multidisciplinary team providing active follow-up and care.

AIMS AND OBJECTIVES: Children suffering from intestinal failure (IF) endure considerable morbidity and overall have poor survival rates, complicated by the shortage of organs available for transplantation. Therefore, new therapeutic approaches are pivotal if outcomes are to be improved. Over the past years, tissue engineering (TE) has emerged as a possible alternative treatment for many congenital and acquired conditions. TE aims at creating bioengineered organs by means of combining scaffolds with appropriate cell types, which in the intestine are organised within a multilayer structure. In order to generate functional intestine, this cellular diversity and organisation will need to be recreated. While the cells for the epithelial, neural and vascular compartments have been well defined, so far, less attention has been put on the muscular compartment. More recently, mesoangioblasts (MABs) have been identified as a novel source for tissue regeneration since they are able to give rise to vascular and other mesodermal derivatives. To date MABs have not been successfully isolated from intestinal tissue. Therefore, our aim was to demonstrate the possibility of isolating MABs from adult mouse small intestine. MATERIALS AND METHODS: All experiments were carried out using small intestinal tissues from C57BL/6J mice. We applied an established protocol for MAB isolation from the isolated neuromuscular layer of the small intestine. Cultured cells were stained for Ki67 to assess proliferation rates as well as for a panel of pericyte markers to determine their phenotype. RESULTS: Cells were successfully isolated from gut biopsies. Cultured cells showed good proliferative capacity and positivity for at least three pericytes markers found in vessels of the gut neuromuscular wall: neuron-glial antigen 2, alkaline phosphatase and platelet-derived growth factor β. CONCLUSION: This proof-of-principle study lays the foundation for further characterization of MABs as a possible cell source for intestinal smooth muscle regeneration and TE. ispartof: PEDIATRIC SURGERY INTERNATIONAL vol:35 issue:1 pages:29-34 ispartof: location:ITALY, Taormina status: published

The current increasing survival of children with severe central nervous system damage has created a major challenge for medical care. Gastrointestinal and nutritional problems in neurologically impaired children have been recently recognized as an integral part of their disease, often leading to growth failure and worsened quality of life for both children and caregivers. Nutritional support is essential for the optimal care of these children. Undernourished handicapped children might not respond properly to intercurrent diseases and suffer unnecessarily. On the other hand, restoring a normal nutritional status results in a better quality of life in many. The easiest and least invasive method to increase energy intake is to improve oral intake. However, oral intake can be maintained as long as there is no risk of aspiration, the child is growing well and the time required to feed the child remains within acceptable limits. When oral intake is unsafe, insufficient or too time consuming, enteral nutrition should be initiated. Damage to the developing central nervous system may result in significant dysfunction in the gastrointestinal tract and is reflected in impairment in oral-motor function, rumination, gastro-oesophageal reflux (GER), with or without aspiration, delayed gastric emptying and constipation. These problems can all potentially contribute to feeding difficulty in disabled children, carrying further challenging long-term management issues.

Recurrent abdominal pain (RAP) is a common complaint in children. Previously considered a single entity, RAP is now used as a descriptive term and sub-classified in the recently published Rome IV criteria, into four functional abdominal pain disorders (FAPD), including functional dyspepsia and irritable bowel syndrome. All share common pathogenic mechanisms of visceral hypersensitivity and central hypervigilance, resulting from disruption of the microbiota–gut–brain axis and abnormal enteric neuro–immune interactions. Although FAPDs are benign in nature, the persistence of symptoms and effects on everyday life can have significant secondary effects including psychosocial morbidity. The diagnosis of FAPDs is based on careful history and examination looking for ‘alarm signs', although a limited battery of laboratory investigations to screen for organic disease may be of value. The management of FAPDs should be multidisciplinary and based on the bio-psychosocial model of care with careful education and engagement of patients/parents. There is currently little evidence to support the routine use of pharmacotherapy, probiotics or diet and a significant placebo effect should be considered when assessing treatment effect. Hypnotherapy has been shown to be an effective therapy. Approximately 50% of FAPDs cases will achieve resolution, especially those that have engaged with the appropriate model of management.

The enteric nervous system (ENS) is involved in the regulation of virtually all gut functions. Conditions referred to as enteric neuropathies are the result of various mechanisms including abnormal development, degeneration or loss of enteric neurons that affect the structure and functional integrity of the ENS. In the past decade, clinical and molecular research has led to important conceptual advances in our knowledge of the pathogenetic mechanisms of these disorders. In this review we consider ENS disorders from a clinical perspective and highlight the advancing knowledge regarding their pathophysiology. We also review current therapies for these diseases and present potential novel reparative approaches for their treatment.

The enteric nervous system (ENS) is required for peristalsis of the gut and is derived from Enteric Neural Crest Cells (ENCCs). During ENS development, the RET receptor tyrosine kinase plays a critical role in the proliferation and survival of ENCCs, their migration along the developing gut, and differentiation into enteric neurons. Mutations in RET and its ligand GDNF cause Hirschsprung disease (HSCR), a complex genetic disorder in which ENCCs fail to colonize variable lengths of the distal bowel. To identify key regulators of ENCCs and the pathways underlying RET signaling, gene expression profiles of untreated and GDNF-treated ENCCs from E14.5 mouse embryos were generated. ENCCs express genes that are involved in both early and late neuronal development, whereas GDNF treatment induced neuronal maturation. Predicted regulators of gene expression in ENCCs include the known HSCR genes Ret and Sox10, as well as Bdnf, App and Mapk10. The regulatory overlap and functional interactions between these genes were used to construct a regulatory network that is underlying ENS development and connects to known HSCR genes. In addition, the adenosine receptor Ala (Adora2a) and neuropeptide Y receptor Y2 (Npy2r) were identified as possible regulators of terminal neuronal differentiation in GDNF-treated ENCCs. The human orthologue of Npy2r maps to the HSCR susceptibility locus 4q31.3-q32.3, suggesting a role for NPY2R both in ENS development and in HSCR. (C) 2016 Elsevier Inc. All rights reserved.

Background Colonic manometry is the standard diagnostic modality for evaluating colonic motility in children. Intraluminal bisacodyl is routinely used to trigger high-amplitude propagating contractions (HAPCs), a feature of normal colonic motility. Usually, only a single dose (0.2 mg/kg) is suggested. We retrospectively explored whether the use of an additional higher (0.4 mg/kg) dose of bisacodyl increases the yield of colonic manometry. Methods In 103 children (median age: 8.8 years, range 3.2–15.7 years) with a diagnosis of slow transit constipation, colonic motility was recorded for 1 h before and 1 h after each of two incremental doses of bisacodyl (low, L, dose: 0.2 mg/kg, max 10 mg; high, H, dose: 0.4 mg/kg, max 20 mg) and the characteristics of HAPCs analyzed. Key Results High-amplitude propagating contractions were seen in 85 children. H dose significantly increased the proportion of patients with fully propagated HAPCs (H dose: 57/103 [55%], L dose: 27/103 [26%], p

Abnormal development or disturbed functioning of the enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, is associated with the development of neuropathic gastrointestinal motility disorders. Here, we review the underlying molecular basis of these disorders and hypothesize that many of them have a common defective biological mechanism. Genetic burden and environmental components affecting this common mechanism are ultimately responsible for disease severity and symptom heterogeneity. We believe that they act together as the fulcrum in a seesaw balanced with harmful and protective factors, and are responsible for a continuum of symptoms ranging from neuronal hyperplasia to absence of neurons.

According to international guidelines, polyethylene glycol (PEG) is the laxative of first choice in the treatment of functional constipation in children, both for disimpaction and for maintenance treatment. PEG acts as an osmotic laxative and its efficacy is dose dependent. PEG is highly effective, has a good safety profile, and is well tolerated by children. Only minor adverse events have been reported. Overall the use of PEG in children has been reported to be safe, although in patients predisposed to water and electrolyte imbalances monitoring of serum electrolytes should be considered.

The bewildering complexity of the enteric nervous system makes it susceptible to develop a wide array of motility disorders, collectively called enteric neuropathies. These gastrointestinal conditions are among the most challenging to manage, mainly given poor characterization of their etiopathophysiology and outcomes. Not surprisingly, therefore, targeted or curative therapies for enteric neuropathies are lacking and management is largely symptomatic. Nonetheless, recent advances in neurogastroenterology have witnessed improvements in established strategies, such as intestinal transplantation and the emergence of new treatments including novel drugs, electrical pacing, and manipulation of fecal microbiota, as well as stem cell and gene therapy.

Pediatric gastrointestinal motility disorders represent a range of severe developmental or acquired conditions that disrupt enteric neuromuscular function. Current medical and surgical therapeutic options are very limited but recent advances have highlighted the possibility of improved or curative stem cell-based treatments. Not only has the ability to harvest, propagate and transplant human-derived enteric neural stem cells (ENSCs) been demonstrated but recent in vivo transplantation studies have confirmed that ENSCs are capable of engraftment within recipient intestine of animal models of enteric neuropathy and effecting functional rescue. Pluripotent stem cell-derived cells and pharmacological modulation of both endogenous and transplanted neural stem cells have further enhanced the exciting prospect of clinical application of such stem cell-based therapies in the near future.

Objectives: Chronic intestinal pseudo-obstructive (CIPO) conditions are considered the most severe disorders of gut motility. They continue to present significant challenges in clinical care despite considerable recent progress in our understanding of pathophysiology, resulting in unacceptable levels of morbidity and mortality. Major contributors to the disappointing lack of progress in paediatric CIPO include a dearth of clarity and uniformity across all aspects of clinical care from definition and diagnosis to management. In order to assist medical care providers in identifying, evaluating, and managing children with CIPO, experts in this condition within the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition as well as selected external experts, were charged with the task of developing a uniform document of evidence- and consensus-based recommendations. Methods: Ten clinically relevant questions addressing terminology, diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was performed from inception to June 2017 using a number of established electronic databases as well as repositories. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate outcome measures for the research questions. Levels of evidence and quality of evidence were assessed using the classification system of the Oxford Centre for Evidence-Based Medicine (diagnosis) and the GRADE system (treatment). Each of the recommendations were discussed, finalized, and voted upon using the nominal voting technique to obtain consensus. Results: This evidence- and consensus-based position paper provides recommendations specifically for chronic intestinal pseudo-obstruction in infants and children. It proposes these be termed paediatric intestinal pseudo-obstructive (PIPO) disorders to distinguish them from adult onset CIPO. The manuscript provides guidance on the diagnosis, evaluation, and treatment of children with PIPO in an effort to standardise the quality of clinical care and improve short- and long-term outcomes. Key recommendations include the development of specific diagnostic criteria for PIPO, red flags to alert clinicians to the diagnosis and guidance on the use of available investigative modalities. The group advocates early collaboration with expert centres where structured diagnosis and management is guided by a multi-disciplinary team, and include targeted nutritional, medical, and surgical interventions as well as transition to adult services. Conclusions: This document is intended to be used in daily practice from the time of first presentation and definitive diagnosis PIPO through to the complex management and treatment interventions such as intestinal transplantation. Significant challenges remain to be addressed through collaborative clinical and research interactions.

BACKGROUND Enteric neuropathies exist as a wide range of human disorders which impact on gastrointestinal motility. Current standard therapies for enteric neuropathies are limited to surgical resection or manipulation (eg, myotomy) of affected gut segments or medical management including both therapy (eg, prokinetic pharmacotherapy) and support such as parenteral nutrition. However, such treatments often result in poor prognosis and significant morbidity. The current limitations in treatment options for enteric neuropathies underline the need for alternative approaches to treat these devastating diseases. Recent advances have highlighted the potential of enteric neural stem cells as a possible treatment option for regenerative medicine, in such cases. PURPOSE The purpose of this review is to provide an up-to-date synopsis of the enteric neural stem cell research field. Here, we review in detail the initial characterization of enteric neural stem cells, early preclinical studies validating their use in murine models through to the most recent findings of therapeutic rescue of diseased gut tissue. We additionally pose a number of questions regarding these recent findings which will need to be addressed prior to clinical translation of this exciting cellular therapeutic.

Gastrointestinal symptoms including constipation, diarrhoea, pain and bloating represent some of the most common clinical problems for patients. These symptoms can often be managed with cheap, widely available medication or will spontaneously resolve. However, for many patients, chronic GI symptoms persist and frequently come to dominate their lives. At one end of the spectrum there is Inflammatory Bowel Disease (IBD) with a clearly defined but expensive treatment pathway. Contrasting with this is Irritable Bowel Syndrome (IBS), likely a collection of pathologies, has a poorly standardised pathway with unsatisfactory clinical outcomes. Managing GI symptoms in adult populations is a challenge. The clinical burden of gastrointestinal disease is also prevalent in paediatric populations and perhaps even harder to treat. In this review we explore some of the recent advances in magnetic resonance imaging (MRI) to study the gastrointestinal tract. Complex in both its anatomical structure and its physiology we are likely missing key physiological markers of disease through relying on symptomatic descriptors of gut function. Using MRI we might be able to characterise previously opaque processes, such as non-propulsive contractility, that could lead to changes in how we understand even common symptoms like constipation. This review explores recent advances in the field in adult populations and examines how this safe, objective and increasingly available modality might be applied to paediatric populations.

Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults.

Objective: T o de v elop a North American Society for Pediatric Ga str oen te rol og y , He pat olo gy , and Nut ri tio n (N ASP GH AN) and Eu rop ea n Soc ie ty fo r Pe di atr ic Gas tr oen te ro log y , Hep at ol og y , and Nut rit io n (ES PGH AN ) int er nat io nal con se ns us on th e di agn os is an d ma nag em ent of gas tr oes op hag eal refl ux and gas tr oes op hag eal re flu x di sea se in th e ped ia tr ic po pu la tio n. Methods: An international panel of 9 pediatric gastroenterologists and 2 epidemiologists were selected by both societies, which de v eloped these guidelines based on the Delphi principle. Statements were based on systematic literature searches using the best-av ailable e vidence from PubMed, Cumulati ve Index to Nursing and Allied Health Literature, and bibliographies. The committee con v ened in face-to-face meetings 3 times. Consensus was achie v ed for all recommendations through nominal group technique, a structured, quantitati v e method. Articles were e v aluated using the Oxford Centre for Evidence-based Medicine Le vels of Evidence. Using the Oxford Grades of Recommendation, the quality of e vidence of each of the recommendations made by the committee was determined and is summarized in appendices. Results: More than 600 articles were re vie wed for this work. The document provides e vidence-based guidelines for the diagnosis and management of gastroesophageal reflux and gastroesophageal reflux disease in the pediatric population. Conclusions: Th is do cum ent is int end ed to be us ed in dai ly pra cti ce fo r th e de v el op me nt of fut ure cli ni cal pra ct ic e gu ide lin es and as a bas is for cli ni cal tr ia ls . JP GN 49 :49 8 – 54 7, 20 09 . Ke y Wo rd s: Cli nic al pra ct ic e gu id el ine s — Di agn os tic te sts — Ga str oes op hag ea l refl ux (GE R) — Ga str oes op hag ea l refl ux di sea se (GE RD ) — The rap eut ic mod al iti es. # 20 09 by Eu rop ea n Soc ie ty fo r Pe di atr ic Gas tr oen te ro log y , Hep at ol og y , and Nut rit io n and No rt h Am er ica n So ci ety for Pe dia tri c Ga str oen te rol og y , Hep at ol og y , an d Nu tr iti on

OBJECTIVE: The clinical relevance of esophageal baseline impedance (BI) remains to be determined. In the present study, we explored the impact of gastroesophageal reflux disease (GERD) and esophageal dysmotility on BI. METHODS: A total of 18 children with esophageal atresia, 26 children with GERD, and 17 controls prospectively underwent esophagogastroduodenoscopy and pH-impedance monitoring. BI was measured in both proximal and distal esophagus. Gastroesophageal reflux (GER) and bolus transit indicators were defined according to published criteria. RESULTS: Patients with esophageal atresia showed significantly lower proximal and distal BI values (952 [716-1811] Ω; 895 [284-1189] Ω; respectively) compared with those with GERD (3015 [2368-3975] Ω; 2231 [1770-3032] Ω, P < 0.001 and

Multichannel intraluminal impedance combined with pH (MII-pH) is the gold standard test for diagnosing gastro-esophageal reflux disease (GERD). It provides an opportunity to study acid and non-acid GOR and temporal association between symptoms and reflux. Accurate catheter placement is essential to prevent erroneous recording of reflux events. The aims of our study were to assess the accuracy of our devised method in predicting the catheter length for MII-pH in children (Great Ormond Street Hospital (GOSH) Table) and to compare the results with Strobel and Monreau methods.Retrospective review of all records of infants and children who underwent MII-pH studies between January to October 2014. Desired catheter position was calculated using Strobel, Monreau and GOSH formulas and compared to X ray position.One hundred and forty-four children were included; mean age was 5.1 (±4.5) years, 73 males and 71 females. In the whole group, the correlation between desired catheter position and GOSH Table was 0.95, for Strobel was 0.84, and Monreau was 0.85. In the first group (age3 years), the correlation was: GOSH Table 0.91, Strobel 0.56, and Monreau 0.6; in the second group (3-10 years): GOSH Table 0.78, Strobel 0.82, and Monreau 0.82; the third group (10 years): GOSH 0.81, Strobel 0.43, and Monreau 0.43.GOSH Table is an accurate method to estimate the insertion length of MII-pH catheters from nares to a point of approximately two vertebral bodies above the diaphragm in children. Although radiography is required to confirm final catheter position, using GOSH Table will reduce the need for repeated catheter manipulation after initial insertion and will reduce the use of a mathematically complicated formulae.

Background The colo-anal reflex is a distinct reflex whereby the internal anal sphincter (IAS) relaxes in association with colonic high amplitude propagating contractions (HAPCs) in contrast to the recto-anal inhibitory reflex (RAIR), which is characterized by IAS relaxation upon rectal distension. The RAIR is mediated by the myenteric plexus and therefore absent in Hirschsprung disease. We retrospectively assessed the presence and the characteristics of the colo-anal reflex in children in whom large bowel continuity had been surgically disrupted to assess the role of the extrinsic nervous system in the reflex. Methods High-resolution (HR) colonic manometry and HR-anorectal manometry were used to evaluate both colonic and anal motor activity in ten children with treatment-unresponsive slow transit constipation (STC), who had previously undergone left-sided colostomy formation with consequent disruption of the bowel continuity, and in two children with Hirschsprung's disease (HSCR), who had previously undergone distal colon resection followed by Duhamel pull-through. Eight children with STC, normal colonic motor activity, and preserved large bowel continuity served as a control group. The presence and characteristics of colo-anal reflex were analyzed. Key results In the study group, all patients showed the presence of both normal HAPCs and the presence of the colo-anal reflex. In two cases of HSCR, RAIR was absent; however, both patients demonstrated a colo-anal reflex. Conclusions In children with disrupted continuity of the colon and/or abnormal anal reflex, the colo-anal reflex is still preserved suggesting that it is mediated by a different pathway from the RAIR, possibly an extrinsic neural pathway.

ObjectivesTo estimate the cost of functional gastrointestinal disorders (FGIDs) and related signs and symptoms in infants to the third party payer and to parents.Study designTo estimate the cost of illness (COI) of infant FGIDs, a two-stage process was applied: a systematic literature review and a COI calculation. As no pertinent papers were found in the systematic literature review, a ‘de novo’ analysis was performed. For the latter, the potential costs for the third party payer (the National Health Service (NHS) in England) and for parents/carers for the treatment of FGIDs in infants were calculated, by using publicly available data. In constructing the calculation, estimates and assumptions (where necessary) were chosen to provide a lower bound (minimum) of the potential overall cost. In doing so, the interpretation of the calculation is that the true COI can be no lower than that estimated.ResultsOur calculation estimated that the total costs of treating FGIDs in infants in England were at least £72.3 million per year in 2014/2015 of which £49.1 million was NHS expenditure on prescriptions, community care and hospital treatment. Parents incurred £23.2 million in costs through purchase of over the counter remedies.ConclusionsThe total cost presented here is likely to be a significant underestimate as only lower bound estimates were used where applicable, and for example, costs of alternative therapies, inpatient treatments or diagnostic tests, and time off work by parents could not be adequately estimated and were omitted from the calculation. The number and kind of prescribed products and products sold over the counter to treat FGIDs suggest that there are gaps between treatment guidelines, which emphasise parental reassurance and nutritional advice, and their implementation.

Feeding difficulties are frequent in children with neurological impairments and can be associated with undernutrition, growth failure, micronutrients deficiencies, osteopenia, and nutritional comorbidities. Gastrointestinal problems including gastroesophageal reflux disease, constipation, and dysphagia are also frequent in this population and affect quality of life and nutritional status. There is currently a lack of a systematic approach to the care of these patients. With this report, European Society of Gastroenterology, Hepatology and Nutrition aims to develop uniform guidelines for the management of the gastroenterological and nutritional problems in children with neurological impairment.Thirty-one clinical questions addressing the diagnosis, treatment, and prognosis of common gastrointestinal and nutritional problems in neurological impaired children were formulated. Questions aimed to assess the nutritional management including nutritional status, identifying undernutrition, monitoring nutritional status, and defining nutritional requirements; to classify gastrointestinal issues including oropharyngeal dysfunctions, motor and sensory function, gastroesophageal reflux disease, and constipation; to evaluate the indications for nutritional rehabilitation including enteral feeding and percutaneous gastrostomy/jejunostomy; to define indications for surgical interventions (eg, Nissen Fundoplication, esophagogastric disconnection); and finally to consider ethical issues related to digestive and nutritional problems in the severely neurologically impaired children. A systematic literature search was performed from 1980 to October 2015 using MEDLINE. The approach of the Grading of Recommendations Assessment, Development, and Evaluation was applied to evaluate the outcomes. During 2 consensus meetings, all recommendations were discussed and finalized. The group members voted on each recommendation using the nominal voting technique. Expert opinion was applied to support the recommendations where no randomized controlled trials were available.

To report outcomes of children with constipation refractory to medical management and manometrically proven distal colonic dysmotility, managed with rectosigmoidectomy followed by Duhamel operation (Duhamel). Children who underwent a Duhamel from 2009 onwards for intractable constipation and left colonic dysmotility were retrospectively reviewed. The primary end point was resolution of constipation, and secondary end point was postoperative complications. Continuous data were median (range). 11 patients (4 males) had Duhamel at 11 years (5–16) with constipation started from 2 years (1–8). Hirschsprung’s disease was excluded. All Duhamels were performed with a covering ileostomy: 9 following a Hartmann procedure, one following a previously failed reversal of Hartmann, and one Duhamel performed with a pre-existing ileostomy. All ileostomies were subsequently closed. Median resection length was 22 cm (11–31). Length of stay was 8 days (5–23). Follow-up was 5 years (0.5–7). Age at final review was 15 years (10–18). Resolution of constipation occurred in nine patients (4 required antegrade continence enemas (ACE), 5 with laxative); two had persistent constipation and faecal incontinence despite ACE, ultimately requiring an ileostomy. Two postoperative small bowel obstructions required laparotomy. Duhamel performed in children with manometrically proven distal colonic dysmotility yielded 82% resolution of refractory constipation; half of them subsequently needed ACE.