The role of high-resolution impedance manometry to identify rumination syndrome in children with unexplained foregut symptoms.

OBJECTIVES: Diagnosis of rumination syndrome (RS) relies on Rome IV criteria. Oesophageal high-resolution impedance manometry (HRIM) can objectively demonstrate the episodes of rumination, but its role in the diagnostic pathway is not yet established. We aimed to demonstrate the clinical contribution of this tool for the timely diagnosis of RS and diagnostic work-up of children with unexplained foregut symptoms deemed to be due to other conditions. METHODS: HRIMs performed between 2012 and 2021 were searched to retrieve all diagnoses of RS. Medical records were reviewed for clinical data. RESULTS: Out of 461 HRIMs performed, 76 children had manometric diagnosis of RS (35 male, median age: 13 years). Of them, 47% were not clinically suspected as the symptoms did not fulfil clinical criteria for RS. The indications for HRIM in these cases were investigation of unexplained foregut symptoms (37%), suspected refractory gastroesophageal reflux disease (8%) and dysphagia (2%). Among all HRIMs performed for investigations of unexplained foregut symptoms (n = 80), 35% demonstrated rumination episodes. CONCLUSION: Identification of characteristic patterns of rumination on HRIM in children with unexplained foregut symptoms enables the immediate diagnosis of RS. Thus, in situations of diagnostic uncertainty, the use of HRIM at early stages of the diagnostic pathway would reduce unnecessary investigations and treatments.

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.

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.

Intra- and Inter-observer Agreement of High Resolution Antroduodenal Manometry in Pediatric Patients Among Single Center Experts.

OBJECTIVES: Studies in adults have suggested that high-resolution technology increases the diagnostic yield of antroduodenal manometry (ADM). However, there is no study comparing high-resolution with low-resolution ADM recordings as well as comparing the 2 types of high-resolution display [conventional line plot (CLP) and pressure topographic plots (PTP)]. We hypothesized that high-resolution ADM is a superior diagnostic modality with higher inter-observer and intra-observer agreement compared with low-resolution recordings. METHODS: Twenty-four anonymized ADM studies were blindly analyzed by 3 experienced pediatric neurogastroenterologists. All studies had been performed using a low-compliance water-perfused system with a 20-channels catheter. Data were displayed as CLP, as both high-resolution and low-resolution, and PTP in different sessions with at least 6-week interval. Accuracy was evaluated using previous established diagnosis and specific pre-prandial and post-prandial manometric patterns. Inter-observer and intra-observer agreements were calculated. RESULTS: Analysis with high-resolution CLP revealed a substantial inter-observer agreement among the 3 observers regarding the diagnosis (Krippendorff's alpha: 0.832; average pairwise percentage agreement: 88.9%). Conversely, PTP and low-resolution CLP showed poor agreement for diagnoses (Krippendorff's alpha: 0.600; average pairwise percentage agreement: 75.3%; Krippendorff's alpha: 0.390; average pairwise percentage agreement: 60.2%, respectively). For the intra-observer agreement, Krippendorff's alpha ranges were 0.891-1 for CLP and 0.19393-0.34621 for PTP. CONCLUSIONS: Our study demonstrated higher diagnostic accuracy for high-resolution ADM compared to the low-resolution recordings. However, although it is well established for other motility investigations, PTP is not yet reliable in assessing foregut motor patterns. Advanced and more sophisticated software are clearly required for analyzing PTP display.

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.

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.

Long-term outcomes of Heller's myotomy and balloon dilatation in childhood achalasia.

Achalasia is a rare esophageal motility disorder: its optimal treatment in children is still a matter of debate. Records of children treated for achalasia, over an 18-year period, were reviewed.Forty-eight children (median age at diagnosis 10 years; range 3-17 years) were identified. Twenty-eight patients were initially treated with Heller's myotomy (HM) and 20 with balloon dilatation (BD). At last follow-up (median 3 years; range 1-5.5 years), 43.8% (21/48) of children were symptom free. The number of asymptomatic children was significantly higher among those treated initially with HM compared to BD (HM 15/28, 53.6% BD 6/20, 30%, p < 0.05). All children who underwent BD required HM due to symptom recurrence. The median (range) total number of procedures was significantly higher in the BD group (BD 3 (1-7); HM 1 (1-5); p < 0.05) with a shorter time to the second intervention (BD 14 months, 95%CI 4-24; HM 58 months, 95%CI 38-79; p < 0.05). Of 108 procedures, esophageal perforation occurred in two children after HM (two out of 48 HM procedures in total, 4%) and one child after BD (1/60, 1.7%). CONCLUSION: Less than half of children with achalasia are symptom free after initial treatment with either BD or HM. HM, however, when performed as first procedure, provided longer symptom-free period and reduced need for subsequent intervention. What is Known: • Balloon dilatation (BD) and Heller's myotomy (HM) are safe and effective treatment options for achalasia. • Controversy, however, exists regarding the most effective initial therapeutic approach. What is New: • HM with or without fundoplication may represent the initial therapeutic approach of choice. • Initial BD may negatively affect the outcome of a subsequent HM.

Duhamel operation for children with distal colonic dysmotility.

PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSION: Duhamel performed in children with manometrically proven distal colonic dysmotility yielded 82% resolution of refractory constipation; half of them subsequently needed ACE.

A mutation in the thyroid hormone receptor alpha gene.

Thyroid hormones exert their effects through alpha (TRα1) and beta (TRß1 and TRß2) receptors. Here we describe a child with classic features of hypothyroidism (growth retardation, developmental retardation, skeletal dysplasia, and severe constipation) but only borderline-abnormal thyroid hormone levels. Using whole-exome sequencing, we identified a de novo heterozygous nonsense mutation in a gene encoding thyroid hormone receptor alpha (THRA) and generating a mutant protein that inhibits wild-type receptor action in a dominant negative manner. Our observations are consistent with defective human TRα-mediated thyroid hormone resistance and substantiate the concept of hormone action through distinct receptor subtypes in different target tissues.

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.

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.

Inflammatory skin and bowel disease linked to ADAM17 deletion.

We performed genetic and immunohistochemical studies in a sister and brother with autosomal recessive neonatal inflammatory skin and bowel lesions. The girl died suddenly at 12 years of age from parvovirus B19-associated myocarditis; her brother had mild cardiomyopathy. We identified a loss-of-function mutation in ADAM17, which encodes a disintegrin and metalloproteinase 17 (also called tumor necrosis factor α [TNF-α]-converting enzyme, or TACE), as the probable cause of this syndrome. Peripheral-blood mononuclear cells (PBMCs) obtained from the brother at 17 years of age showed high levels of lipopolysaccharide-induced production of interleukin-1ß and interleukin-6 but impaired release of TNF-α. Despite repeated skin infections, this young man has led a relatively normal life. (Funded by Barts and the London Charity and the European Commission Seventh Framework Programme.).

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.

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.

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.

Transpyloric propagation and liquid gastric emptying in children with foregut dysmotility.

BACKGROUND/OBJECTIVES: Gastric emptying (GE) requires precise antropyloroduodenal coordination for effective transpyloric flow, the mechanisms of which are still unclear. We aimed to correlate gastric antral function assessed by antroduodenal manometry (ADM) with GE scintigraphy (GES) for liquid feeds in children with suspected gastrointestinal dysmotility. METHODS: Children who underwent both ADM and GES over a five-year period were reviewed. ADM tracings were re-analyzed to assess antral frequency, amplitude, and motility index (MI) pre-prandially and postprandially. Transpyloric propagation (TPP) was defined as antegrade propagated antral activity preceding duodenal phase III of the migrating motor complex (MMC). TPP was defined as "poor" if occurring in <50% of all presented duodenal phases III. For GES, regions of interest over the whole stomach, fundus, and antrum were drawn to calculate GE half-time (GE-T1/2 ) and retention rate (RR) in each region at 1 and 2 h. RESULTS: Forty-seven children (median age: 7.0 years) were included. Twenty-two had PIPO, 14 functional GI disorders, and 11 gastroparesis. Children with poor TPP had longer GE-T1/2 (113.0 vs 66.5 min, p = 0.028), higher RR of the whole stomach and fundus at 1 h (79.5% vs 63.5%, p = 0.038; 60.0% vs 41.0%, p = 0.022, respectively) and 2 h (51.0% vs 10.5%, p = 0.005; 36.0% vs 6.5%, p = 0.004, respectively). The pre-prandial antral amplitude of contractions inversely correlated with GE-T1/2 , RR of the whole stomach, and fundus at 2 h. CONCLUSIONS: TPP during phase III of the MMC correlated with gastric emptying of liquid and its assessment on ADM might predict abnormalities in postprandial gastric function.

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.

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.

Pediatric esophageal high-resolution manometry: utility of a standardized protocol and size-adjusted pressure topography parameters.

OBJECTIVES: Esophageal high-resolution manometry (EHRM) has evolved rapidly from a research tool to a routine investigation in adult clinical practice. This study proposes and evaluates a standardized EHRM protocol for use in pediatric clinical practice. METHODS: Thirty pediatric patients underwent unsedated EHRM. Indications for EHRM were dysphagia, feeding difficulty, or pre-fundoplication assessment. Two 20-channel customized water-perfused silicone catheters, with an outside diameter of 3.8 mm (MuiScientific, Ontario, CA), were used. The catheters had one distal gastric channel, five channels 0.5 cm apart for the e-sleeve, and 14 proximal channels either 1 cm (for children <5 years) or 2 cm apart (for children >5 years). Single wet swallows, multiple rapid swallows (MRS), and solid swallows were systematically studied. RESULTS: The median age was 10 years (range 6 months-15 years). The esophageal motor findings were normal peristalsis (n=15), peristaltic dysfunction (n=12), achalasia (n=3), and spasm on consumption of solid food (n=2). The distal contractile integral adjusted for esophageal length (DCIa) of patients with peristaltic dysfunction was significantly lower than that of patients without peristaltic dysfunction (P<0.001). On MRS, aperistalsis with lack of esophagogastric junction (EGJ) relaxation was observed in patients with achalasia, and aperistalsis with complete EGJ relaxation was observed in patients with severe peristaltic dysfunction. On consumption of solid food, esophageal spasm associated with bolus impaction was observed in two patients. CONCLUSIONS: This study provides objective information with regard to topography pressure parameters in esophageal motility disorders of childhood while using a standardized EHRM protocol. The new DCIa variable may be useful for the assessment of patients with peristaltic dysfunction.