IntroductionAchalasia is a rare neurodegenerative esophageal motility disorder characterized by incomplete lower esophageal sphincter (LES) relaxation, increased LES tone and absence of esophageal peristalsis. Achalasia requires invasive treatment in all patients. Conventional treatment options include endoscopic balloon dilation (EBD) and laparoscopic Heller's myotomy (LHM). Recently, a less invasive endoscopic therapy has been developed; Peroral Endoscopic Myotomy (POEM). POEM integrates the theoretical advantages of both EBD and LHM (no skin incisions, less pain, short hospital stay, less blood loss and a durable myotomy). Our aim is to compare efficacy and safety of POEM vs. EBD as primary treatment for achalasia in children.Methods and analysisThis multi-center, and center-stratified block-randomized controlled trial will assess safety and efficacy of POEM vs EBD. Primary outcome measure is the need for retreatment due to treatment failure (i.e. persisting symptoms (Eckardt score > 3) with evidence of recurrence on barium swallow and/or HRM within 12 months follow-up) as assed by a blinded end-point committee (PROBE design).DiscussionThis RCT will be the first one to evaluate which endoscopic therapy is most effective and safe for treatment of naïve pediatric patients with achalasia.

OBJECTIVE:To develop a core outcome set for clinical studies assessing gastroesophageal reflux disease (GERD) in children. STUDY DESIGN:This core outcome set was developed using a 2-round Delphi technique and adhering to the Outcome Measures in Rheumatology Initiative (OMERACT 2.0) recommendations. Healthcare professionals (HCPs) and (parents of) children (age 1-18 years) with a GERD diagnosis (ie, the presence of bothersome symptoms), listed up to 5 harmful and/or beneficial outcomes that they considered important in the treatment of GERD. Outcomes mentioned by more than 10% of participants were put forward and rated and prioritized by HCPs, parents, and children in a second round. Outcomes with the highest rank formed the draft core outcome set. The final core outcome set was created during an online consensus meeting between an expert panel. RESULTS:The first round was completed by 118 of 125 HCPs (94%), 146 of 146 parents (100%), and 69 of 70 children (99%). A total of 80 of 118 HCPs (68%), 130 of 140 parents (93%), and 77 children (100%) completed round 2. "Adequate relief," "evidence of esophagitis," "feeding difficulties," "heartburn (≥4 years)," "hematemesis," "regurgitation," "sleeping difficulties," "vomiting," and "adverse events" were included in the final core outcome set for GERD in children aged 1-18 years. CONCLUSIONS:We identified a total set of 9 core outcomes and suggest these outcomes to be minimally measured in clinical studies assessing GERD in children. Implementation of this core outcome set is likely to increase comparison between studies and may thus provide future recommendations to improve treatment of GERD in children.

Objectives: Pediatric high-resolution manometry (HRM) and 24-hour pH-impedance with/without ambulatory manometry (pH-MII+/-mano) tests are generally performed using adult-derived protocols. We aimed to assess the feasibility of these protocols in children, the occurrence of patient-related imperfections and their influence on test interpretability. Methods: Esophageal function tests performed between 2015 and 2018 were retrospectively analyzed. All tests were subcategorized into uninterpretable or interpretable tests (regardless of occurrence of patient-related imperfections). For HRM, the following patient-related imperfections were scored: patient-related artefacts, multiple swallowing and/or inability to establish baseline characteristics. For pH-MII(+/-mano), incorrect symptom registration and/or premature catheter removal were scored. Results were compared between age-groups (0-3, 4-12, and >12 years). Results: In total 106 HRM, 60 pH-MII, and 23 pH-MII-mano could be fully analyzed. Of these, 94.8% HRM, 91.9% pH-MII, and 95.7% pH-MII-mano were interpretable. Overall, HRM contained imperfections in 78.3% overall and in 8/8 (100%) in the youngest age group, 36/42 (85.7%) in 4 to 12 years and in 37/56 (66.1%) in children above 12 years; P = 0.011. These imperfections led to uninterpretable results in 4 HRM (3.8%), of which 3 were in the youngest age group (3/8, 37.5%). Imperfections were found in 10% of pH-MII and 17.4% of pH-MII-mano. These led to uninterpretable results in 5.0% and 4.3%, respectively. No age-effect was found. Conclusions: Esophageal function tests in children are interpretable in more than 90% overall. In children under the age of 4 years, all patients had imperfect HRM and 3/8 tests were uninterpretable. HRM in older children and pH-MII+/-mano were interpretable in the vast majority.

The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant's microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed "settler types", based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children's cohorts based on settler types may reveal group effects that might otherwise be masked.

The diagnosis and management of gastroesophageal reflux disease (GERD) in children remains a challenge. Recently, the North American and European Societies for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN and ESPGHAN respectively) came out with a new guideline on pediatric GERD. This article provides an overview of evidence-based and expert opinion recommendations for the diagnosis and management of GERD in children.

Functional gastrointestinal disorders (FGIDs) are common in infants and toddlers and are characterized by chronic or recurrent gastrointestinal symptoms that cannot be explained by structural or biochemical abnormalities. This article sheds light on the most common FGIDs in infants and toddlers, including regurgitation and gastroesophageal reflux (GER), infant dyschezia, functional constipation, functional diarrhea, and infant colic. This article describes the background, pathophysiology, diagnostic evaluation, and management strategies of these FGIDs.

Oesophageal atresia (EA) is a congenital abnormality of the oesophagus that is caused by incomplete embryonic compartmentalization of the foregut. EA commonly occurs with a tracheo-oesophageal fistula (TEF). Associated birth defects or anomalies, such as VACTERL association, trisomy 18 or 21 and CHARGE syndrome, occur in the majority of patients born with EA. Although several studies have revealed signalling pathways and genes potentially involved in the development of EA, our understanding of the pathophysiology of EA lags behind the improvements in surgical and clinical care of patients born with this anomaly. EA is treated surgically to restore the oesophageal interruption and, if present, ligate and divide the TEF. Survival is now ~90% in those born with EA with severe associated anomalies and even higher in those born with EA alone. Despite these achievements, long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common and lead to decreased quality of life. Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair and often underlie these complications and comorbidities. The implementation of several new diagnostic and screening tools in clinical care, including high-resolution impedance manometry, pH-multichannel intraluminal impedance testing and disease-specific quality of life questionnaires now provide better insight into these problems and may contribute to better long-term outcomes in the future.

BACKGROUND:High-resolution esophageal manometry (HREM), derived esophageal pressure topography metrics (EPT), integrated relaxation pressure (IRP), and distal latency (DL) are influenced by age and size. Combined pressure and intraluminal impedance also allow derivation of metrics that define distension pressure and bolus flow timing. We prospectively investigated the effects of esophageal length on these metrics to determine whether adjustment strategies are required for children. METHODS:Fifty-five children (12.3 ± 4.5 years) referred for HREM, and 30 healthy adult volunteers (46.9 ± 3.8 years) were included. Studies were performed using the MMS system and a standardized protocol including 10 × 5 mL thin liquid bolus swallows (SBM kit, Trisco Foods) and analyzed via Swallow Gateway (www.swallowgateway.com). Esophageal distension pressures and swallow latencies were determined in addition to EGJ resting pressure and standard EPT metrics. Effects of esophageal length were examined using partial correlation, correcting for age. Adult-derived upper limits were adjusted for length using the slopes of the identified linear equations. KEY RESULTS:Mean esophageal length in children was 16.8 ± 2.8 cm and correlated significantly with age (r = 0.787, P = .000). Shorter length correlated with higher EGJ resting pressure and 4-s integrated relaxation pressures (IRP), distension pressures, and shorter contraction latencies. Ten patients had an IRP above the adult upper limit. Adjustment for esophageal length reduced the number of patients with elevated IRP to three. CONCLUSIONS & INFERENCES:We prospectively confirmed that certain EPT metrics, as well as potential useful adjunct pressure-impedance measures such as distension pressure, are substantially influenced by esophageal length and require adjusted diagnostic thresholds specifically for children.

Objective To systematically review definitions of functional abdominal pain orders (FAPDs) and outcome measures used in therapeutic randomized controlled trials in pediatric FAPDs adhering to the Outcome Measures in Rheumatology recommendations. Study design Cochrane, MEDLINE, Embase, and Cinahl databases were systematically searched from inception to April 2018. English-written therapeutic randomized controlled trials concerning FAPDs in children aged 4-18 years were included. Definitions of FAPDs, interventions, outcome measures, measurement instruments, and outcome assessors of each study were tabulated descriptively. Quality was assessed using the Delphi List. Results A total of 4771 articles were found, of which 64 articles were included (n = 25, 39% of high methodologic quality). The Rome III (50%), Rome II (17%), Apley (16%), and author-defined (17%) criteria were used to define FAPDs. Fourteen studies (22%) assessed a pharmacologic, 25 (39%) a dietary, and 25 (39%) a psychosocial intervention. Forty-four studies (69%) predefined their primary outcomes. In total, 211 reported predefined outcome measures were grouped into 23 different outcome domains; the majority being patient-reported (n = 27, 61 %). Of the 14 studies that evaluated a pharmacologic intervention, 12 (86%) reported on adverse events. Conclusions Studies on pediatric FAPDs are of limited methodologic quality and show large heterogeneity and inconsistency in defining FAPDs and outcome measures used. Development of a core outcome set is needed to make comparison between intervention studies possible.

ABSTRACTObjectives:Gastroesophageal reflux disease (GERD) is defined as gastroesophageal reflux causing troublesome symptoms or complications. In this study we reviewed the literature regarding the prevalence of GERD symptoms in infants and children.Methods:Databases of PubMed, EMBASE, and Cochrane were systematically searched from inception to June 26, 2018. English‐written studies based on birth cohort, school‐based, or general population samples of ≥50 children aged 0 to 21 years were included. Convenience samples were excluded.Results:In total, 3581 unique studies were found, of which 25 studies (11 in infants and 14 in children) were included with data on the prevalence of GERD symptoms comprising a total population of 487,969 children. In infants (0–18 months), GERD symptoms are present in more than a quarter of infants on a daily basis and show a steady decline in frequency with almost complete disappearance of symptoms at the age of 12 months. In children older than 18 months, GERD symptoms show large variation in prevalence between studies (range 0%‐38% of study population) and overall, are present in >10% and in 25% on respectively a weekly and monthly basis. Of the risk factors assessed, higher body mass index and the use of alcohol and tobacco were associated with higher GERD symptom prevalence.Conclusions:This systematic review demonstrates that the reported prevalence of GERD symptoms varies considerably, depending on method of data collection and criteria used to define symptoms. Nevertheless, the high reported prevalence rates support better investment of resources and educational campaigns focused on prevention.

ABSTRACT In this systematic review, we summarize the evidence on prognosis and prognostic factors of pediatric gastroesophageal reflux disease (GERD). A structured search of Embase and MEDLINE/PubMed (inception to April 2016) yielded 5365 references; 4 publications met our inclusion criteria (risk of bias moderate‐high). Definitions and outcome measures varied widely between studies. The percentage of children with a diagnosis of GERD with esophagitis that had persisting symptoms and/or were on antireflux medication at follow‐up (12 months to >5 years) ranged from 23% (weekly symptoms) to 68% (antireflux medication), depending on definition used. In children with a diagnosis of GERD without esophagitis, 1.4% developed esophagitis at follow‐up (>5 years); none developed Barrett esophagus. In conclusion, prognostic studies on pediatric GERD are of limited quality and show large methodological heterogeneity. Based on these studies, we are unable to identify those children at risk for unfavorable outcome with regards to GERD symptoms or endoscopic complications.

Background High-resolution impedance manometry (HRIM) allows evaluation of esophageal bolus retention, flow, and pressurization. We explored novel HRIM measures and assessed their temporal relationship to dysphagia symptoms for boluses of different volume and consistency in non-obstructive dysphagia (NOD) patients. Methods Thirty-three NOD patients (n = 19 minor or no disorder of peristalsis ("Normal") and n = 14 esophagogastric junction outflow obstruction ("EGJOO")) were evaluated with HRIM. Patients were administered 5 and 10 mL liquid, semisolid, and 2 and 4 cm solid boluses and indicated bolus perception during individual swallows using a 5-point Likert scale. HRIM was analyzed to assess Chicago Classification and pressure flow metrics, esophageal impedance integral (EII) ratio, and bolus flow time (BFT). Key Results Overall, bolus perception increased with increasing bolus consistency (P < 0.001), but did not differ significantly between EGJOO and Normal patients. EGJOO patients had higher IRP4, higher levels of bolus residual (ie, EII ratio and IR), and restricted esophageal emptying. The results for linking semisolid bolus perception to semisolid-derived measures revealed more biomechanically plausible and consistent patterns when compared to those derived for liquid boluses. In Normal patients, perception of boluses of heavier viscosity was related to higher bolus flow resistance during transport, whilst in EGJOO, perception was related to restriction of esophageal emptying. Conclusion & Inferences These novel pressure-impedance measures may aid in the evaluation of NOD patients by revealing abnormal motor patterns, which may explain symptom generation. Future studies are needed to evaluate which of these measures are worthy of calculation and to establish protocol settings that allow for their meaningful interpretation.

In this systematic review, we summarize the evidence on prognosis and prognostic factors of pediatric gastroesophageal reflux disease (GERD). A structured search of Embase and MEDLINE/PubMed (inception to April 2016) yielded 5365 references; 4 publications met our inclusion criteria (risk of bias moderate-high). Definitions and outcome measures varied widely between studies. The percentage of children with a diagnosis of GERD with esophagitis that had persisting symptoms and/or were on antireflux medication at follow-up (12 months to >5 years) ranged from 23% (weekly symptoms) to 68% (antireflux medication), depending on definition used. In children with a diagnosis of GERD without esophagitis, 1.4% developed esophagitis at follow-up (>5 years); none developed Barrett esophagus. In conclusion, prognostic studies on pediatric GERD are of limited quality and show large methodological heterogeneity. Based on these studies, we are unable to identify those children at risk for unfavorable outcome with regards to GERD symptoms or endoscopic complications.

This document serves as an update of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2009 clinical guidelines for the diagnosis and management of gastroesophageal reflux disease (GERD) in infants and children and is intended to be applied in daily practice and as a basis for clinical trials. Eight clinical questions addressing diagnostic, therapeutic and prognostic topics were formulated. A systematic literature search was performed from October 1, 2008 (if the question was addressed by 2009 guidelines) or from inception to June 1, 2015 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Clinical Trials. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to define and prioritize outcomes. For therapeutic questions, the quality of evidence was also assessed using GRADE. Grading the quality of evidence for other questions was performed according to the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) and Quality in Prognostic Studies (QUIPS) tools. During a 3-day consensus meeting, all recommendations were discussed and finalized. In cases where no randomized controlled trials (RCT; therapeutic questions) or diagnostic accuracy studies were available to support the recommendations, expert opinion was used. The group members voted on each recommendation, using the nominal voting technique. With this approach, recommendations regarding evaluation and management of infants and children with GERD to standardize and improve quality of care were formulated. Additionally, 2 algorithms were developed, 1 for infants <12 months of age and the other for older infants and children.

Neurogastroenterology & MotilityVolume 30, Issue 10 e13452 LETTER TO THE EDITOR Letter in response to Rosen et al.: An interesting pediatric case of rumination syndrome Maartje M. J. Singendonk, Maartje M. J. Singendonk m.m.j.singendonk@amc.uva.nl orcid.org/0000-0001-9297-4790 Department of Pediatric Gastroenterology and Nutrition, Emma Children’s Hospital/Amsterdam UMC - location AMC, Amsterdam, The NetherlandsSearch for more papers by this authorMarc A. Benninga, Marc A. Benninga Department of Pediatric Gastroenterology and Nutrition, Emma Children’s Hospital/Amsterdam UMC - location AMC, Amsterdam, The NetherlandsSearch for more papers by this authorMichiel P. van Wijk, Michiel P. van Wijk orcid.org/0000-0002-8112-8414 Department of Pediatric Gastroenterology, Amsterdam UMC, location VUmc, Amsterdam, Amsterdam, The NetherlandsSearch for more papers by this authorRammy Abu-Assi, Rammy Abu-Assi Gastroenterology Unit, Women’s & Children’s Hospital, Adelaide, North Adelaide, AustraliaSearch for more papers by this authorTaher I. Omari, Taher I. Omari orcid.org/0000-0001-5108-7378 College of Medicine and Public Health, Flinders University, Adelaide, South Australia, AustraliaSearch for more papers by this author Maartje M. J. Singendonk, Maartje M. J. Singendonk m.m.j.singendonk@amc.uva.nl orcid.org/0000-0001-9297-4790 Department of Pediatric Gastroenterology and Nutrition, Emma Children’s Hospital/Amsterdam UMC - location AMC, Amsterdam, The NetherlandsSearch for more papers by this authorMarc A. Benninga, Marc A. Benninga Department of Pediatric Gastroenterology and Nutrition, Emma Children’s Hospital/Amsterdam UMC - location AMC, Amsterdam, The NetherlandsSearch for more papers by this authorMichiel P. van Wijk, Michiel P. van Wijk orcid.org/0000-0002-8112-8414 Department of Pediatric Gastroenterology, Amsterdam UMC, location VUmc, Amsterdam, Amsterdam, The NetherlandsSearch for more papers by this authorRammy Abu-Assi, Rammy Abu-Assi Gastroenterology Unit, Women’s & Children’s Hospital, Adelaide, North Adelaide, AustraliaSearch for more papers by this authorTaher I. Omari, Taher I. Omari orcid.org/0000-0001-5108-7378 College of Medicine and Public Health, Flinders University, Adelaide, South Australia, AustraliaSearch for more papers by this author First published: 26 September 2018 https://doi.org/10.1111/nmo.13452Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume30, Issue10October 2018e13452 RelatedInformation

OBJECTIVE:In achalasia, absent peristalsis and reduced esophagogastric junction (EGJ) relaxation and compliance underlie dysphagia symptoms. Novel high-resolution impedance manometry variables, that is, bolus presence time (BPT) and trans-EGJ-bolus flow time (BFT) have been developed to estimate the duration of EGJ opening and trans-EGJ bolus flow. The aim of this study was to evaluate esophageal motor function and bolus flow in children diagnosed with achalasia using these variables.METHODS:High-resolution impedance manometry recordings from 20 children who fulfilled the Chicago Classification (V3) criteria for achalasia were compared with recordings of 15 children with normal esophageal high-resolution manometry findings and no other evidence suggestive of achalasia. Matlab-based analysis software was used to calculate BPT and BFT.RESULTS:Both BPT and BFT were significantly reduced in achalasia patients compared with children with normal esophageal motility (BPT 3.3 s vs 5.1 s P < 0.01; BFT 1.4 s vs 4.3 s P < 0.001). BFT was significantly lower than BPT (achalasia difference 1.9 s ± 1.3 s, P = 0.001 and normal difference 0.9 ± 0.3 s, P = 0.001). Overall, there was a significant correlation between BPT and BFT (r = 0.825, P < 0.001). We observed a 2-way differentiation of achalasia patients; those in whom the BPT and BFT were proportional, but significantly lower than in patients with normal peristalsis, and those in whom BFT was disproportionately lower than BPT.CONCLUSIONS:Calculation of BPT and BFT may help determine whether esophageal bolus transport to the EGJ and/or esophageal emptying through the EGJ are aberrant. For achalasia, this may detect flow resistance at the EGJ, potentially improving both diagnosis and objective assessment of therapeutic effects.

A noninvasive test for gastroesophageal reflux disease (GERD) is desirable for adults and children. Salivary pepsin measurement has been proposed as such a test.1-3 A previous study from our group demonstrated that a maximal salivary pepsin cutoff of >210 ng/mL using the PepTest device (RD Biomed, Hull, United Kingdom) had excellent specificity of 96% but modest sensitivity of 44% to diagnose GERD,4 leading to optimism about its potential use. In this study, we aimed to confirm the previously reported sensitivity and specificity in healthy volunteers and patients with heartburn, evaluate the association between a positive PepTest and response to proton pump inhibitor (PPI) therapy, assess if test-sensitivity can be improved for GERD when samples are taken over a 72-hour sampling period, and establish normal values of salivary pepsin in infants.