New insights in gastroesophageal reflux, esophageal function and gastric emptying in relation to dysphagia before and after anti-reflux surgery in children.

This item is under embargo for a period of 12 months from the date of publication, in accordance with the publisher's policy.In children with gastroesophageal reflux (GER) disease refractory to pharmacological therapies, anti-reflux surgery (fundoplication) may be a treatment of last resort. The applicability of fundoplication has been hampered by the inability to predict which patient may benefit from surgery and which patient is likely to develop post-operative dysphagia. pH impedance measurement and conventional manometry are unable to predict dysphagia, while the role of gastric emptying remains poorly understood. Recent data suggest that the selection of patients who will benefit from surgery might be enhanced by automated impedance manometry pressure-flow analysis (AIM) analysis, which relates bolus movement and pressure generation within the esophageal lumen

Esophageal impedance baselines in infants before and after placebo and proton pump inhibitor therapy

Author version made available in accordance with the publisher's policy.ABSTRACT Background Esophageal impedance monitoring records changes in conductivity. During esophageal rest impedance baseline values may represent mucosal integrity. The aim of this study was to assess the influence of acid suppression on impedance baselines in a placebo controlled setting. Material and Methods Impedance recordings from 40 infants (0-6months) enrolled in randomized placebo controlled trials of proton pump inhibitor (PPI) were retrospectively analyzed. Infants underwent 24hr pH-impedance monitoring prior to and after two weeks of double blind therapy with placebo or a PPI. Typical clinical signs of gastroesophageal reflux (GER) were recorded and I-GERQ-R questionnaire was completed. Key results Median (IQR) impedance baseline increased on PPI treatment (from 1217 (826-1514) to 1903 (1560-2194) Ohm, p<0.001) but not with placebo (from 1445 (1033-1791) to 1650 (1292-1983) Ohm, p=0.13). Baselines before treatment inversely correlate with the number of GER, acid GER, weakly acid GER, acid exposure and symptoms. The change in baseline on treatment inversely correlates with acid exposure and acid GER. Patients with initial low baselines have no improved symptomatic response to treatment. Conclusions and Inferences Impedance baselines are influenced by GER and increase significantly more with PPI therapy than with placebo. Clinical impact of this observation remains undefined as targeting therapy at infants with low baselines does not improve symptomatic response to treatment

Pressure-Flow Characteristics of Normal and Disordered Esophageal Motor Patterns

Copyright © 2015 Elsevier Inc. All rights reserved This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Objective To perform pressure-flow analysis (PFA) in a cohort of pediatric patients who were referred for diagnostic manometric investigation. Study design PFA was performed using purpose designed Matlab-based software. The pressure-flow index (PFI), a composite measure of bolus pressurization relative to flow and the impedance ratio, a measure of the extent of bolus clearance failure were calculated. Results Tracings of 76 pediatric patients (32 males; 9.1 ± 0.7 years) and 25 healthy adult controls (7 males; 36.1 ± 2.2 years) were analyzed. Patients mostly had normal motility (50%) or a category 4 disorder and usually weak peristalsis (31.5%) according to the Chicago Classification. PFA of healthy controls defined reference ranges for PFI ≤142 and impedance ratio ≤0.49. Pediatric patients with pressure-flow (PF) characteristics within these limits had normal motility (62%), most patients with PF characteristics outside these limits also had an abnormal Chicago Classification (61%). Patients with high PFI and disordered motor patterns all had esophagogastric junction outflow obstruction. Conclusions Disordered PF characteristics are associated with disordered esophageal motor patterns. By defining the degree of over-pressurization and/or extent of clearance failure, PFA may be a useful adjunct to esophageal pressure topography-based classification

Novel pressure-impedance parameters for evaluating esophageal function in pediatric achalasia

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

Intra- and interrater reliability of the Chicago Classification of achalasia subtypes in pediatric High Resolution Esophageal Manometry (HRM) recordings

This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'. © 2017 John Wiley & Sons, Inc. All rights reserved. This author accepted manuscript is made available following 12 month embargo from date of publication (June 2017) in accordance with the publisher’s archiving policyBackground Subtyping achalasia by high‐resolution manometry (HRM) is clinically relevant as response to therapy and prognosis have shown to vary accordingly. The aim of this study was to assess inter‐ and intrarater reliability of diagnosing achalasia and achalasia subtyping in children using the Chicago Classification (CC) V3.0. Methods Six observers analyzed 40 pediatric HRM recordings (22 achalasia and 18 non‐achalasia) twice by using dedicated analysis software (ManoView 3.0, Given Imaging, Los Angeles, CA, USA). Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), intrabolus pressurization pattern (IBP), and distal latency (DL) were extracted and analyzed hierarchically. Cohen's κ (2 raters) and Fleiss’ κ (>2 raters) and the intraclass correlation coefficient (ICC) were used for categorical and ordinal data, respectively. Results Based on the results of dedicated analysis software only, intra‐ and interrater reliability was excellent and moderate (κ=0.89 and κ=0.52, respectively) for differentiating achalasia from non‐achalasia. For subtyping achalasia, reliability decreased to substantial and fair (κ=0.72 and κ=0.28, respectively). When observers were allowed to change the software‐driven diagnosis according to their own interpretation of the manometric patterns, intra‐ and interrater reliability increased for diagnosing achalasia (κ=0.98 and κ=0.92, respectively) and for subtyping achalasia (κ=0.79 and κ=0.58, respectively). Conclusions Intra‐ and interrater agreement for diagnosing achalasia when using HRM and the CC was very good to excellent when results of automated analysis software were interpreted by experienced observers. More variability was seen when relying solely on the software‐driven diagnosis and for subtyping achalasia. Therefore, diagnosing and subtyping achalasia should be performed in pediatric motility centers with significant expertise

Objectively diagnosing rumination syndrome in children using esophageal pH-impedance and manometry

This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'. © 2017 John Wiley & Sons, Inc. All rights reserved.Background Rumination syndrome is characterized by recurrent regurgitation of recently ingested food into the mouth. Differentiation with other diagnoses and gastroesophageal reflux disease (GERD) in particular, is difficult. Recently, objective pH‐impedance (pH‐MII) and manometry criteria were proposed for adults. The aim of this study was to determine diagnostic ambulatory pH‐MII and manometry criteria for rumination syndrome in children. Methods Clinical data and 24‐hour pH‐MII and manometry recordings of children with a clinical suspicion of rumination syndrome were reviewed. Recordings were analyzed for retrograde bolus flow extending into the proximal esophagus. Peak gastric and intraesophageal pressures closely related to these events were recorded and checked for a pattern compatible with rumination. Events were classified into primary, secondary, and supragastric belch–associated rumination. Key Results Twenty‐five consecutive patients (11 males, median age 13.3 years [IQR 5.9‐15.8]) were included; recordings of 18 patients were suitable for analysis. Rumination events were identified in 16/18 patients, with 50% of events occurring 30 mmHg, while only 50% of all events was characterized by peaks >30 mmHg and an additional 20% by peaks >25 mmHg. Four patients had evidence of acid GERD, all showing secondary rumination. Conclusions and Inferences Combined 24‐hour pH‐MII and manometry can be used to diagnose rumination syndrome in children and to distinguish it from GERD. Rumination patterns in children are similar compared with adults, albeit with lower gastric pressure increase. We propose a diagnostic cutoff for gastric pressure increase >25 mmHg associated with retrograde bolus flow into the proximal esophagus

Inter- and intra-rater reliability of the Chicago Classification in pe-diatric high-resolution esophageal manometry recordings

This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'.Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.Background The Chicago Classification (CC) facilitates interpretation of high-resolution manometry (HRM) recordings. Application of this adult based algorithm to the pediatric population is unknown. We therefore assessed intra and interrater reliability of software-based CC diagnosis in a pediatric cohort. Methods Thirty pediatric solid state HRM recordings (13M; mean age 12.1 ± 5.1 years) assessing 10 liquid swallows per patient were analyzed twice by 11 raters (six experts, five non-experts). Software-placed anatomical landmarks required manual adjustment or removal. Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), contractile front velocity (CFV), distal latency (DL) and break size (BS), and an overall CC diagnosis were software-generated. In addition, raters provided their subjective CC diagnosis. Reliability was calculated with Cohen's and Fleiss’ kappa (κ) and intraclass correlation coefficient (ICC). Key Results Intra- and interrater reliability of software-generated CC diagnosis after manual adjustment of landmarks was substantial (mean κ = 0.69 and 0.77 respectively) and moderate-substantial for subjective CC diagnosis (mean κ = 0.70 and 0.58 respectively). Reliability of both software-generated and subjective diagnosis of normal motility was high (κ = 0.81 and κ = 0.79). Intra- and interrater reliability were excellent for IRP4s, DCI, and BS. Experts had higher interrater reliability than non-experts for DL (ICC = 0.65 vs ICC = 0.36 respectively) and the software-generated diagnosis diffuse esophageal spasm (DES, κ = 0.64 vs κ = 0.30). Among experts, the reliability for the subjective diagnosis of achalasia and esophageal gastric junction outflow obstruction was moderate-substantial (κ = 0.45–0.82). Conclusions & Inferences Inter- and intrarater reliability of software-based CC diagnosis of pediatric HRM recordings was high overall. However, experience was a factor influencing the diagnosis of some motility disorders, particularly DES and achalasia

Evaluation of exclusive enteral nutrition and corticosteroid induction treatment in new-onset moderate-to-severe luminal paediatric Crohn's disease

To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the "TISKids" study assigned to the conventional treatment arm. Patients were aged 3-17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI)> 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10.Peer reviewe

Diagnosis and management in Rubinstein-Taybi syndrome: first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care