Small Bowel Transit Scintigraphy in Children With Pediatric Intestinal Pseudo-Obstruction.

INTRODUCTION: Objective evidence of small intestinal dysmotility is a key criterion for the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Small bowel scintigraphy (SBS) allows for objective measurement of small bowel transit (SBT), but limited data are available in children. We aimed to evaluate the utility of SBS in children suspected of gastrointestinal dysmotility. METHODS: Patients undergoing gastric emptying studies for suspected foregut dysmotility, including PIPO, from 2016 to 2022 at 2 tertiary children's hospitals were recruited to an extended protocol of gastric emptying studies to allow for assessment of SBT. PIPO was classified based on antroduodenal manometry (ADM). SBT was compared between PIPO and non-PIPO patients. Scintigraphic parameters were assessed and correlated against ADM scores. RESULTS: Fifty-nine patients (16 PIPO and 43 non-PIPO diagnoses) were included. SBS was performed with liquid and solid meals in 40 and 26 patients, respectively. As compared to the non-PIPO group, PIPO patients had a significantly lower median percentage of colonic filling at 6 hours, with both liquid (48% vs 83%) and solid tests (5% vs 65%). SBT in PIPO patients with myopathic involvement was significantly slower than in patients with neuropathic PIPO, both for liquid and solid meal. A significant correlation was found between solid SBT and ADM scores (r = -0.638, P = 0.036). DISCUSSION: SBS provides a practically feasible assessment of small intestinal motility. It shows a potential utility to help diagnose and characterize PIPO. SBS seems most discriminative in PIPO patients with myopathic involvement. Studies in a larger pediatric population and across different ages are required.

Optimizing nutrition IN pediatric intestinal pseudo-obstruction syndrome.

BACKGROUND: Pediatric intestinal pseudo-obstruction (PIPO) encompasses a variety of rare, heterogeneous, and disabling disorders that severely affect gastrointestinal motility and are associated with high morbidity and mortality. PIPO management is complex and focuses on maintaining an optimal nutritional status, improving gut function, relieving symptoms, and treating complications. Nutritional issues prevail, and PIPO patients often experience severe undernutrition and faltering growth. Thus, nutritional management plays a pivotal role for achieving the most favorable clinical outcomes. The calorie and nutrient intake of each patient needs to be tailored to age, extent and severity of gut involvement and nutritional needs to support an optimal nutritional status. After defining the extent and severity of gut dysmotility, an experienced team should perform a careful nutritional assessment. An oral diet should always be encouraged and might include bite and dissolve solids, liquid diet or simple oral stimulation. If oral caloric intake is inadequate, liquid gastric feeds should provide the subsequent step. In the presence of severe gastric dysmotility, continuous post-pyloric feeding represents a viable option. In the most severe cases, parenteral nutrition (PN) is required to meet appropriate nutritional requirements. PURPOSE: Pediatric data on this topic are scarce and mainly extrapolated from adult studies. In this review, we discuss current evidence and knowledge regarding nutritional options, implications of the use of different feed types, including a blended diet, and the use of PN. Moreover, based on our experience and the evidence from the literature, we propose a flow chart to guide the nutritional management of PIPO patients.

Prevalence of gastrointestinal disorders in individuals with RASopathies: May RAS/MAP/ERK pathway dysfunctions be a model of neuropathic pain and visceral hypersensitivity?

RASopathies are a group of neurodevelopmental syndromes caused by germline variants in genes of the Ras/MAP/ERK pathway. Growth failure, neurological involvement, and pain represent the main features of these conditions. ERK signaling cascade plays a crucial role in nociception and visceral pain and it is likely implicated in the genesis of neuropathic pain and maintenance of altered pain states. We studied the prevalence of abdominal pain and functional gastrointestinal (GI) disorders in a large sample of individuals with RASopathies. A brief pain inventory questionnaire and semi-structured dedicated interview were used to investigate presence and localization of pain. A Rome IV questionnaire was used to screen for functional GI disorders. Eighty patients with clinical and molecular diagnoses of RASopathy were recruited (42 with Noonan syndrome; 17 with Costello Syndrome and 21 with cardio-facio-cutaneous syndrome). Overall, the prevalence of abdominal pain was 44% and prevalence of functional GI disorders was 78% with constipation, abdominal pain, and aerophagia being the most frequently detected ones. A significant association was found between pain and irritable bowel syndrome, functional constipation and aerophagia. Children with RASopathies have a high prevalence of functional gastrointestinal disorders. These children could represent a good in vivo model to study neuropathic pain, visceral hypersensitivity and gut-brain axis disorders.

Enhancing the utility of antroduodenal manometry in pediatric intestinal pseudo-obstruction.

BACKGROUND: Antroduodenal manometry (ADM) and histopathology are currently employed to aid the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Limited data are available on the reliability of ADM analysis and its correlation with histopathology. We aimed to develop a protocol for enhanced analysis of ADM contractile patterns, including a scoring system, and explore whether this provided better correlation with histopathology. METHODS: Children referred with suspected PIPO between April 2012-December 2019 who underwent both ADM and full-thickness biopsies were included. ADM tracings were analyzed using both standard (conventional ADM) and novel (enhanced ADM) motility parameters. A novel ADM score (GLASS score) was generated based on the enhanced ADM analysis. Conventional and enhanced ADM analyses were then correlated with histopathology. RESULTS: Forty patients were included. Using conventional clinical criteria, 29 of these were diagnosed with PIPO and the other 11 with non-PIPO diagnoses. Twenty-three of the PIPO patients had abnormal histopathology: 6 myopathy, 4 neuropathy, 3 neuro-myopathy, and 10 non-specific changes. No agreement in diagnosis was found between conventional ADM analysis and histopathology (Ï° = 0.068; p = 0.197), whereas the latter significantly correlated with enhanced ADM analysis (Ï° = 0.191; p = 0.003). The enhanced ADM score was significantly higher in PIPO versus non-PIPO (16.0 vs. 8.0; p < 0.001). CONCLUSIONS: As opposed to conventional analysis protocols, the newly developed enhanced ADM analysis and associated score is not only able to discriminate between PIPO and non-PIPO patients, but also between distinct histopathological pathologies. Further studies are required to assess the utility of enhanced ADM analysis in larger populations.

Mucosal Abnormalities in Children With Congenital Chloride Diarrhea-An Underestimated Phenotypic Feature?

Objectives and Study: Congenital chloride diarrhea (CCD) is a rare, autosomal recessive disorder caused by mutations in the SLC26A3 gene encoding a transmembrane chloride/bicarbonate ion exchanger mainly expressed in the apical brush border of the ileal and colonic epithelium. Lifelong, secretory, chloride-rich diarrhea and hypochloremic, hypokalemic metabolic alkalosis are characteristic. Histological evidence of bowel inflammation is not typically described in CCD and has only been reported in a few patients. Methods: We report four cases of CCD who received adequate resuscitation with appropriate replacement of their fecal salt and water losses. Three had associated inflammatory bowel changes at endoscopy. The index case of CCD who developed frankly bloodstained diarrhea aged 7 months was found to have histologically confirmed colitis at endoscopy. An electronic search of the hospital database to identify all patients with confirmed CCD was performed. A further three children underwent de novo diagnostic evaluation and treatment. A retrospective case note review was undertaken to determine the incidence and subtype of inflammatory bowel disease (IBD) by clinical, endoscopic, and histological means. Results: Four children with genetically confirmed CCD were identified, two being female. The first girl had a granulomatous colitis with ulceration. She went into remission with a combination of steroids and azathioprine. Immunosuppression was subsequently discontinued without a further flare of colitis. A second girl was found to have patchy inflammatory changes in the small bowel and focal active colitis. A third patient, a boy, demonstrated mild inflammatory changes in the small bowel with apoptotic debris and mild inflammation in the colon. A fourth patient did not develop intestinal inflammation. Conclusion: Our case series highlights the potential association of CCD with panenteric inflammation. While our cohort was small, CCD is rare and three out of four children referred to our tertiary referral center were affected. While early diagnosis and adequate salt replacement therapy are crucial in CCD management, the clinician should also be aware of bowel inflammation as a potential cause of failure of CCD therapy to control bowel symptomatology. Further insight is needed to understand the underlying patho-mechanism giving rise to bowel inflammation in this group.

Diagnosis and management of children with Blue Rubber Bleb Nevus Syndrome: A multi-center case series.

BACKGROUND: Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare, severe, sporadically occurring disorder characterized by multiple venous malformations. AIMS: To present and analyze a case series of pediatric patients with BRBNS and to describe diagnostic approaches and management options applied. PATIENTS AND METHODS: Multicenter, retrospective study, evaluating the diagnosis and management of children with BRBNS. RESULTS: Eighteen patients diagnosed with BRBNS were included. Cutaneous venous malformations were observed in 78% and gastrointestinal venous malformations in 89%. Lesions were also found in other organs including muscles, joints, central nervous system, eyes, parotid gland, spine, kidneys and lungs. Gastrointestinal lesions were more common in the small intestine than in stomach or colon. The management varied significantly among centers. Endoscopic therapy and surgical therapy alone failed to prevent recurrence of lesions. In younger children and in patients with musculoskeletal or other organ involvement, sirolimus was used with 100% success rate in our series (5 patients treated) although poor compliance with subtherapeutic sirolimus trough levels led to recurrence in a minority. CONCLUSIONS: Considering the multi-organ involvement in BRBNS, diagnosis and management requires a multidisciplinary approach. The treatment includes conservative, medical, endoscopic and surgical options. Prospective multicenter studies are needed to identify the optimal management of this rare condition.

Is There a Role for pH Impedance Monitoring in Identifying Eosinophilic Esophagitis in Children with Esophageal Atresia?

OBJECTIVES: To evaluate clinical, endoscopic, and pH-impedance measures in a cohort of children with esophageal atresia and concomitant eosinophilic esophagitis (EoE) and compared it with disease-matched controls, to identify predictive factors for the development of EoE and esophageal stricture. STUDY DESIGN: We reviewed 63 patients with esophageal atresia assessed for refractory upper gastrointestinal symptoms between January 2015 and September 2017 at 2 tertiary referral centers. All patients underwent upper gastrointestinal endoscopy and pH-impedance monitoring. Based on esophageal histology, patients were classified as (1) esophageal atresia without evidence of esophagitis; (2) esophageal atresia with evidence of esophagitis (including esophageal eosinophilia not meeting the criteria for EoE); (3) esophageal atresia with concomitant EoE. Age and sex matched patients with gastroesophageal reflux disease were used as disease controls. RESULTS: The presence of atopy and peripheral eosinophilia at baseline were significantly associated with EoE (P < .05). Although there was a tendency toward an increased number of strictures in patients with esophageal atresia-EoE, this did not reach statistical significance (P = .06). Higher esophageal acid exposure time and lower baseline impedance values were significantly associated with eosinophilic infiltration (P < .05 and P < .01, respectively). Using logistic regression analysis, the presence of mucosal eosinophilia was the most predictive factor for stricture formation (P < .05). CONCLUSIONS: A history of atopy and the presence of peripheral eosinophilia in patients with esophageal atresia are predictive factors for the development of EoE, which in turn is a predictive factor for stricture occurrence. Higher esophageal acid exposure time and lower baseline impedance are associated with esophageal eosinophilic infiltration, suggesting their value in selecting which patients with esophageal atresia should undergo endoscopic examination.

Preservation of the colo-anal reflex in colonic transection and post-operative Hirschsprung's disease: Potential extrinsic neural pathway.

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.

Paediatric pancreaticobiliary endoscopy: a 21-year experience from a tertiary hepatobiliary centre and systematic literature review.

BACKGROUND: In adults ERCP and endoscopic ultrasound (EUS) are standard methods of evaluating and treating many hepatopancreaticobiliary (HPB) conditions. HPB disease is being diagnosed with increasing frequency in children but information about role of ERCP and EUS and their outcomes in this population remain limited. Therefore the aims of this study were to describe the paediatric ERCP and EUS experience from a large tertiary referral HPB centre, and to systematically compare outcomes with those of other published series. METHODS: All patients <18 years undergoing an ERCP or EUS between January 1992-December 2014 were included. Indications for the procedure, rates of technical success, procedural adverse events and reinterventions were recorded in all cases. RESULTS: Ninety children underwent 111 procedures (87 ERCPs and 24 EUS). 53% (48) were female with a median age of 14 years (range: 3 months - 17 years). Procedures were performed under general anaesthesia (n = 48) or conscious sedation (n = 63). Common indications for ERCP included chronic or recurrent pancreatitis and biliary obstruction. Patients frequently had multiple comorbidities, with a median ASA grade of 2 (range 1-4). Therapeutic procedures performed included biliary or pancreatic sphincterotomy, common bile duct or pancreatic duct stone removal, biliary or pancreatic stent insertion, EUS-guided fine needle aspiration and endoscopic transmural drainage of pancreatic fluid collections. No adverse events were reported following ERCP but there was one complication requiring surgery following EUS guided cystenterostomy. CONCLUSION: ERCP and EUS in children and adolescents have high technical success rates and low rates of adverse events when performed in high volume HPB centres.

Effect of Bowel Cleansing on Colonic Transit Time Measurement in Children with Chronic Constipation.

We evaluated the effect of bowel preparation on colonic transit time (CTT) measured by the radio-opaque marker test in children with constipation. All children underwent 2 radio-opaque marker-CTT tests, both in cleansed and uncleansed bowel state. Our findings confirm that the state of colonic fecal filling may significantly influence CTT.

Adalimumab as a second-line biological therapy in children with refractory ulcerative colitis.

AIM: The role of adalimumab in medically refractory ulcerative colitis (UC) in children remains to be defined. The aim of this study was to describe 11 cases of paediatric patients who received adalimumab as a second-line anti-TNF-α treatment for paediatric UC. METHODS: A retrospective review of all patients with UC who received adalimumab between April 2008 and October 2013 at our hospital was conducted. Clinical efficacy and safety were assessed. RESULTS: Eleven patients (three boys, eight girls) with a median age of 13.8 years (5.7-16.6 years) were included. All patients had been previously treated with infliximab. Six patients achieved and maintained clinical remission, with a median duration of treatment of 25 months. One patient was successfully weaned off adalimumab after 26 months of therapy. Treatment was unsuccessful in four out of 11 patients (36%) who underwent colectomy 4-13 months (median 7 months) from the first adalimumab dose. The remaining patient developed extensive rash and was switched to alternative therapy. CONCLUSION: In this case series, our experience shows that there is a role for adalimumab as a combination therapy in a subgroup of children with refractory UC.

Clinical relevance of esophageal baseline impedance measurement: just an innocent bystander.

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 <0.001, respectively) and controls (3699 [3194-4358] Ω; 3522 [2927-3994] Ω, P < 0.001 and <0.001, respectively). Using linear regression, proximal BI strongly correlated with total bolus transit time (r(2) = 0.61, P < 0.001) and bolus presence time (BPT; r(2) = 0.63, P < 0.001). Distal BI weakly correlated with acid exposure time (r(2) = 0.16, P < 0.01) and longstanding reflux episodes (r(2) = 0.17, P < 0.01), and strongly correlated with total bolus transit time (r(2) = 0.53, P < 0.001) and BPT (r(2) = 0.58, P < 0.001). By logistic regression, BPT predicted low proximal BI values (odds ratio [OR] 1.052; P < 0.05), whereas both GER indicators (acid exposure time: OR 1.56, P < 0.05; longstanding reflux episodes: OR 2.8, P < 0.05) and BPT (OR 1.66, P < 0.01) predicted low distal BI values. CONCLUSIONS: Along the length of esophagus, both bolus transit variables and GER significantly affect BI. This suggests that BI may merely mirror phenomena occurring within the esophageal lumen or wall, limiting its value as a discrete clinical entity to replace variables already used for assessing both GERD and esophageal dysmotility.

Four year follow-up of a randomised controlled trial comparing open and laparoscopic Nissen fundoplication in children.

OBJECTIVE: To evaluate the 4-year results following a randomised controlled trial (RCT) comparing open (ONF) and laparoscopic (LNF) Nissen fundoplication in children. BACKGROUND: It is assumed that long-term results of ONF and LNF are comparable. No randomised studies have been performed in children. METHODS: A follow-up study was performed in children randomised to ONF or LNF (clinicaltrials.gov identifier NCT00259961). Recurrent gastro-oesophageal reflux (GER) was documented by upper gastrointestinal contrast study and/or 24-h pH study. Nutritional status, retching and other symptoms were investigated. A questionnaire was used to assess the quality of life before and after surgery. RESULTS: Thirty-nine children were randomised to ONF (n=20) or LNF (n=19). There were 15 ONF and 16 LNF neurologically impaired children. One patient (ONF group) was lost to follow-up. Follow-up was 4.1 years (3.1-5.3) for ONF group and 4.1 years (2.6-5.1) for LNF group (p=0.9). Seven neurologically impaired children had died by the time of follow-up (3 ONF, 4 LNF). Incidence of recurrent GER was 12.5% in the ONF and 20% in the LNF (p=ns). One patient in each group underwent redo-Nissen fundoplication. Nutritional status improved in both groups, as indicated by a significant increase in weight Z-score (p<0.01). Gas bloat and dumping syndrome were present in both groups (p=ns). Incidence of retching was lower in the laparoscopic group (p=0.01). Quality of life improved in both groups (p=ns). CONCLUSIONS: Open and laparoscopic Nissen provide similar control of reflux and quality of life at follow-up. LNF is associated with reduced incidence of retching persisting at 4-year follow-up. TRIAL REGISTRATION NUMBER: NCT00259961.

A distinct mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) phenotype associates with YARS2 mutations.

Nuclear-encoded disorders of mitochondrial translation are clinically and genetically heterogeneous. Genetic causes include defects of mitochondrial aminoacyl-tRNA synthetases, and factors required for initiation, elongation and termination of protein synthesis as well as ribosome recycling. We report on a new case of myopathy, lactic acidosis and sideroblastic anemia (MLASA) syndrome caused by defective mitochondrial tyrosyl aminoacylation. The patient presented at 1 year with anemia initially attributed to iron deficiency. Bone marrow aspirate at 5 years revealed ringed sideroblasts but transfusion dependency did not occur until 11 years. Other clinical features included lactic acidosis, poor weight gain, hypertrophic cardiomyopathy and severe myopathy leading to respiratory failure necessitating ventilatory support. Long-range PCR excluded mitochondrial DNA rearrangements. Clinical diagnosis of MLASA prompted direct sequence analysis of the YARS2 gene encoding the mitochondrial tyrosyl-tRNA synthetase, which revealed homozygosity for a known pathogenic mutation, c.156C>G;p.F52L. Comparison with four previously reported cases demonstrated remarkable clinical homogeneity. First line investigation of MLASA should include direct sequence analysis of YARS2 and PUS1 (encoding a tRNA modification factor) rather than muscle biopsy. Early genetic diagnosis is essential for counseling and to facilitate appropriate supportive therapy. Reasons for segregation of specific clinical phenotypes with particular mitochondrial aminoacyl tRNA-synthetase defects remain unknown.

Oesophageal mucosal intercellular space diameter and reflux pattern in childhood erosive and non-erosive reflux disease.

BACKGROUND AND AIMS: We sought to compare intercellular space diameter in children with non-erosive and erosive reflux disease, and a control group. We also aimed to characterize the reflux pattern in erosive and non-erosive reflux disease patients, and to explore the relationship between intercellular space diameter values and reflux parameters. METHODS: Twenty-four children with non-erosive reflux disease, 20 with erosive reflux disease, and 10 controls were prospectively studied. All patients and controls underwent upper endoscopy. Biopsies were taken at 2-3 cm above the Z-line, and intercellular space diameter was measured using transmission electron microscopy. Non-erosive and erosive reflux disease patients underwent impedance-pH monitoring. RESULTS: Mean intercellular space diameter values were significantly higher in both non-erosive (0.9 ± 0.2 µm) and erosive reflux disease (1 ± 0.2 µm) compared to controls (0.5 ± 0.2 µm, p<0.01). No difference was found between the two patient groups. Acid exposure time, the number of acid, weakly acidic and weakly alkaline reflux events did not differ between the two patient groups. No difference was found in the mean intercellular space diameter between non-erosive reflux disease children with and without abnormal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 µm). No correlation was found between any reflux parameter and intercellular space diameter values. CONCLUSIONS: Dilated intercellular space diameter seems to be a useful and objective marker of oesophageal damage in paediatric gastro-oesophageal reflux disease, regardless of acid exposure. In childhood, different gastro-oesophageal reflux disease phenotypes cannot be discriminated on the basis of reflux pattern.

Cow's milk challenge increases weakly acidic reflux in children with cow's milk allergy and gastroesophageal reflux disease.

OBJECTIVE: To assess and compare the pattern of reflux in a selected population of infants with cow's milk (CM) allergy (CMA) and suspected gastroesophageal reflux disease (GERD) while on dietary exclusion and following challenge with CM. STUDY DESIGN: Seventeen children (median age: 14 months) with a proven diagnosis of CMA and suspected GERD underwent 48-hour multichannel intraluminal impedance-pH monitoring. For the first 24 hours, the infants were kept on amino acid-based formula, and for the subsequent 24 hours, they were challenged with CM. RESULTS: The total reflux episodes and the number of weakly acidic episodes were higher during CM challenge compared with the amino acid-based formula period [total reflux episodes: 105 (58-127.5) vs 65 (39-87.5), P < .001; weakly acidic episodes: 53 (38.5-60.5) vs 19 (13-26.5), P < .001; median (25th-75th)]. No differences were found for either acid or weakly alkaline episodes (not significant). The number of weakly acidic episodes reaching the proximal, mid, and distal esophagus was higher during CM challenge (P < .001). No differences were found in either acid exposure time or number of long-lasting episodes (not significant). CONCLUSIONS: In children with CMA and suspected GERD, CM exposure increases the number of weakly acidic reflux episodes. CM challenge during 48-hour multichannel intraluminal impedance-pH monitoring identifies a subgroup of patients with allergen-induced reflux, and in selected cases of children with CMA in whom GERD is suspected, its use could be considered as part of diagnostic work-up.

Gastrointestinal endoscopy and mucosal biopsy in the first year of life: indications and outcome.

OBJECTIVES: Lower threshold and widening indications for paediatric gastrointestinal endoscopy have resulted in a significant increase in the numbers of endoscopic procedures performed in infants. Despite this, knowledge of gastrointestinal mucosal findings in this age group is limited and data on the clinical usefulness of endoscopy are lacking. METHODS: All of the children younger than 1 year referred to a single tertiary paediatric gastroenterology unit during the period June 1987 to August 2007 who underwent gastrointestinal endoscopy were identified and the clinical indications and histological outcomes were reviewed. RESULTS: A total of 933 gastroesophageal duodenoscopies and 439 colonoscopies were performed in 1024 cases in a total of 823 infants. In order of frequency, clinical indications were diarrhoea (51%), failure to thrive (41.2%), symptoms of reflux (27.1%), and rectal bleeding (8.5%). Mucosal biopsies were insufficient for assessment in only 2.4% of cases. Mucosal histology was normal in 33.8%, whereas histological abnormalities were identified in 63.8%. Specific histological diagnoses included microvillous inclusion disease, autoimmune enteropathy, graft-versus-host disease post-bone marrow transplantation, tufting enteropathy, and disaccharidase deficiency. There was only 1 colonic perforation complicating endoscopy in a total of 889 cases for which relevant information was available (0.1%). CONCLUSIONS: In two-thirds of cases, histological abnormalities were detected that influenced management following endoscopic examination and mucosal biopsy in infants. Endoscopy with biopsies is a greatly informative test with low failure and complication rates in the first year of life.

Role of gastroesophageal reflux in children with unexplained chronic cough.

OBJECTIVE: The relation between respiratory symptoms and gastroesophageal reflux (GER) is a matter of contention and debate, with limited data in children to substantiate or refute cause and effect. Moreover, there are few data on the relation between nonacid reflux and chronic cough in childhood. We aimed to describe the type and physical characteristics of reflux episodes in children with unexplained chronic cough. PATIENTS AND METHODS: Forty-five children with chronic cough underwent 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH monitoring). Symptom association probability (SAP) characterized the reflux-cough association. Twenty children with erosive reflux disease (ERD) served as controls. RESULTS: Twenty-four children had cough-related reflux (CRR), with 19 having no gastrointestinal symptoms. Twenty-one had cough-unrelated reflux (CUR). CRR and ERD had increased acid (AR), weakly acidic (WAc), and weakly alkaline (WAlk) reflux. Esophageal acid exposure time and acid clearance time were higher in ERD than in CRR and CUR. In the CRR group, of 158 cough episodes related to reflux episodes, 66% involved AR, 18% WAc, and 16% WAlk. Seventeen children had positive SAP, 7 for AR, 5 for both AR and WAc, 4 for both WAc and WAlk, and 1 for WAlk. CONCLUSIONS: In children with unexplained chronic cough, asymptomatic acid and nonacid GER is a potential etiologic factor. The increased acid exposure time and delayed acid clearance characteristic of ERD are absent in cough-related GER. MII-pH monitoring increases the likelihood of demonstrating a temporal association between the cough and all types of reflux.

Electrogastrography abnormalities appear early in children with diabetes type 1.

OBJECTIVE: The objective of the study was to evaluate gastric myoelectrical activity in young patients with diabetes and to correlate it with their metabolic control [fasting blood glucose, glycosylated haemoglobin, and fructosamine] and BMI during a 3 years follow-up. METHODS: Surface electrogastrography (EGG) was performed on 49 children with diabetes aged 10.3±4.4 (mean±SD) years and 17 age-matched healthy controls after fasting glucose, glycosylated haemoglobin, and fructosamine were measured. EGG parameters [percentage of bradygastria, 3 cycles per minute, tachygastria, dominant frequency instability coefficient, and power ratio] were analysed and compared with blood analysis. RESULTS: Patients with diabetes exhibited an increase in preprandial bradygastria 7.9±8.8 cpm (mean±SD) compared with controls 2.1±1.0 (P=0.011), with an associated decrease in preprandial normogastria (72.2±14.5 vs. 82.7±14.7; P=0.013). Normogastric power ratio (postprandial/ preprandial power) was significantly increased in the children with diabetes compared with controls (mean: 6.67 vs. 3.14, P=0.034). A longer duration of diabetes was associated with an increased risk of EGG abnormalities (P=0.036). Marked hyperglycaemia at the time of study was associated with postprandial bradygastria (P=0.01) and power ratio bradygastria (P=0.042). Changes in glycosylated haemoglobin, fructosamine and BMI did not affect EGG parameters. CONCLUSIONS: EGG abnormalities, presented early in a high proportion of diabetic children, are related to the acute hyperglycaemia. These abnormalities are not consistently present in the follow-up studies and not related to the glycosylated haemoglobin and fructosamine. Diabetic autonomic neuropathy is therefore an unlikely pathogenic factor for EGG abnormalities in children with diabetes.

Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection.

BACKGROUND: Campylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Despite the significant health burden this infection presents, molecular understanding of C. jejuni-mediated disease pathogenesis remains poorly defined. Here, we report the characterisation of the early, innate immune response to C. jejuni using an ex-vivo human gut model of infection. Secondly, impact of bacterial-driven dendritic cell activation on T-cell mediated immunity was also sought. METHODOLOGY: Healthy, control paediatric terminal ileum or colonic biopsy tissue was infected with C. jejuni for 8-12 hours. Bacterial colonisation was followed by confocal microscopy and mucosal innate immune responses measured by ELISA. Marked induction of IFNγ with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1ß and IL-6 were indicative of a cytokine milieu that may modulate subsequent T-cell mediated immunity. C. jejuni-driven human monocyte-derived dendritic cell activation was followed by analyses of T cell immune responses utilising flow cytometry and ELISA. Significant increase in Th-17, Th-1 and Th-17/Th-1 double-positive cells and corresponding cytokines was observed. The ability of IFNγ, IL-22 and IL-17 cytokines to exert host defence via modulation of C. jejuni adhesion and invasion to intestinal epithelia was measured by standard gentamicin protection assay. CONCLUSIONS: Both innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFNγ, IL-22 and IL-17A; suggesting a critical role for this cytokine triad in establishing host anti-microbial immunity during the acute and effectors phase of infection. In addition, to their known anti-microbial functions; IL-17A and IL-17F reduced the number of intracellular C. jejuni in intestinal epithelia, highlighting a novel aspect of how IL-17 family members may contribute to protective immunity against C. jejuni.