Ineffective esophageal motility: Characterization and outcomes across pediatric neurogastroenterology and motility centers in the United States.

OBJECTIVES: Ineffective esophageal motility (IEM) on high-resolution manometry (HRM) is not consistently associated with specific clinical syndromes or outcomes. We evaluated the prevalence, clinical features, management, and outcomes of pediatric IEM patients across the United States. METHODS: Clinical and manometric characteristics of children undergoing esophageal HRM during 2021-2022 were collected from 12 pediatric motility centers. Clinical presentation, test results, management strategies, and outcomes were compared between children with IEM and normal HRM. RESULTS: Of 236 children (median age 15 years, 63.6% female, 79.2% Caucasian), 62 (23.6%) patients had IEM, and 174 (73.7%) patients had normal HRM, with similar demographics, medical history, clinical presentation, and median symptom duration. Reflux monitoring was performed more often for IEM patients (25.8% vs. 8.6%, p = 0.002), but other adjunctive testing was similar. Among 101 patients with follow-up, symptomatic cohorts declined in both groups in relation to the initial presentation (p > 0.107 for each comparison) with management targeting symptoms, particularly acid suppression. Though prokinetics were used more often and behavioral therapy less often in IEM (p ≤ 0.015 for each comparison), symptom outcomes were similar between IEM and normal HRM. Despite a higher proportion with residual dysphagia on follow-up in IEM (64.0% vs. 39.1%, p = 0.043), an alternate mechanism for dysphagia was identified more often in IEM (68.8%) compared to normal HRM (27.8%, p = 0.017). CONCLUSIONS: IEM is a descriptive manometric pattern rather than a clinical diagnosis requiring specific intervention in children. Management based on clinical presentation provides consistent symptom outcomes.

Consensus on intake questionnaire data elements in the development of an aerodigestive registry.

OBJECTIVE: To define the essential elements of the intake questionnaire that will be a part of a larger multicenter registry for aerodigestive patients. METHODS: A modified Delphi method was utilized to obtain consensus on the data elements that should warrant inclusion in the final research database. Patient questionnaires from the eight participating institutions were reviewed and individual elements were aggregated into 14 categories. RESULTS: A total of 198 initial elements were voted on for inclusion. The categories included demographics, respiratory symptoms, gastrointestinal symptoms, ear nose and throat symptoms, feeding, birth history, medical history, surgical history, family history, social history, medications prior to evaluation, devices used prior to evaluation, prior diagnostic evaluations, and prior evaluation by aerodigestive team members. 83 of the 198 elements met consensus for inclusion in the final registry for an inclusion rate of 41.9 %. Three separate rounds of ranking were required to obtain consensus. CONCLUSION: The aerodigestive registry is an important initiative that will help foster research and help guide future management. The intake questionnaire of the registry is a critical component of this project, and the consensus obtained during this study should help create a streamlined and efficient registry that will help all aerodigestive patients on a national level.

Laryngeal clefts in Prader-Willi syndrome: Feeding difficulties and aspiration not always caused by hypotonia.

Feeding difficulties, aspiration, and failure to thrive in infancy are commonly seen in patients with Prader-Willi Syndrome (PWS) and attributed to hypotonia. Patients with PWS and laryngeal clefts were identified by review of medical records at three tertiary care children's hospitals between 2017 and 2022. We present three patients with PWS with feeding difficulties who were also found to have laryngeal clefts which likely contributed to their feeding difficulties. Additional factors such as airway anomalies should be considered in patients with PWS, especially when swallowing dysfunction, dysphagia, or abnormal swallow evaluations are present.

A multicenter registry study on percutaneous electrical nerve field stimulation for pediatric disorders of gut-brain interaction.

OBJECTIVES: Percutaneous electrical nerve field stimulation (PENFS) has demonstrated promise in single-center trials for pediatric abdominal pain-related disorders of gut-brain interaction (DGBI). Our aim was to explore efficacy of PENFS as standard therapy for DGBI in a registry involving multiple pediatric gastroenterology referral centers. METHODS: This was a multicenter, prospective open-label registry of children (8-18 years) undergoing PENFS for DGBI at seven tertiary care gastroenterology clinics. DGBI subtypes were classified by Rome IV criteria. Parents and patients completed Abdominal Pain Index (API), Nausea Severity Scale (NSS), and Functional Disability Inventory (FDI) questionnaires before, during therapy and at follow-up visits up to 1 year later. RESULTS: A total of 292 subjects were included. Majority (74%) were female with median (interquartile range [IQR]) age 16.3 (14.0, 17.7) years. Most (68%) met criteria for functional dyspepsia and 61% had failed ≥4 pharmacologic therapies. API, NSS, and FDI scores showed significant declines within 3 weeks of therapy, persisting long-term in a subset. Baseline (n = 288) median (IQR) child-reported API scores decreased from 2.68 (1.84, 3.58) to 1.99 (1.13, 3.27) at 3 weeks (p < 0.001) and 1.81 (0.85, 3.20) at 3 months (n = 75; p < 0.001). NSS scores similarly improved from baseline, persisting at three (n = 74; p < 0.001) and 6 months later (n = 55; p < 0.001). FDI scores displayed similar reductions at 3 months (n = 76; p = 0.01) but not beyond. Parent-reported scores were consistent with child reports. CONCLUSIONS: This large, comprehensive, multicenter registry highlights efficacy of PENFS for gastrointestinal symptoms and functionality for pediatric DGBI.

Triple endoscopy and recurrent croup in children: A single aerodigestive center experience.

OBJECTIVE: To determine the utility of triple endoscopy (combined direct laryngoscopy, bronchoscopy (DLB), flexible bronchoscopy with bronchoalveolar lavage (FB + BAL), and esophagogastroduodenoscopy (EGD)) in the diagnosis and management of patients with recurrent croup (RC), and to identify predictors of endoscopic findings METHODS: A retrospective chart review was performed of pediatric patients (age <18 years) with RC evaluated by triple endoscopy at a tertiary care pediatric hospital from 2010 to 2021. Data including presenting symptoms, airway findings, BAL and EGD with biopsy findings were collected. RESULTS: 42 patients with RC underwent triple endoscopy were included. The mean age was 4.55±2.84 years old. The most common symptom was chronic cough among 19 (45%) patients, while 23 (55%) patients had gastrointestinal (GI) symptoms. Airway findings included tracheomalacia in 19, laryngeal cleft in 17, and subglottic stenosis in 11 patients. On EGD with biopsy, abnormal gross findings were present in 6 and abnormal microscopic findings in 18 patients, including 6 with histologic findings suggestive of gastroesophageal reflux and 5 with eosinophilic esophagitis. Seventeen (40%) patients had positive culture on BAL. No findings in patient histories significantly predicted presence of lower airway malacia, subglottic stenosis, or abnormal EGD findings. CONCLUSIONS: Children with recurrent croup presenting to aerodigestive centers may not have any pertinent presenting symptoms that correlate with significant findings on triple endoscopy. Further work is needed to determine which children with recurrent croup may benefit from aerodigestive evaluation. LEVEL OF EVIDENCE: Level 3.

Diagnostic Utility of Mucosal Biopsies Taken During Colonoscopy-Guided Colonic Manometry Catheter Placement.

OBJECTIVES: The diagnostic utility of mucosal biopsies taken during colonoscopy-guided colonic manometry catheter placement is unknown. The aims of our study were to determine the frequency and histopathology results of mucosal biopsies during these procedures and to assess whether there were any associations between the histology or gross findings with manometry results. METHODS: We performed a retrospective chart review of children who had a colonic manometry study completed between 2008 and 2020 at a quaternary children's hospital. We captured patient demographics, biopsy locations, histopathology results, gross endoscopy findings, and manometry results. The chi-squared test and when appropriate Fisher exact test was used to evaluate categorical associations. RESULTS: One hundred forty-eight patients were included. One hundred eighteen (80%) had colonic biopsy and 63 (43%) had ileal biopsy. Colonic histology findings, which patients could have multiple, included lymphonodular hyperplasia (34%), normal (27%), chronic inflammation (24%), melanosis coli (21%), colonic eosinophilia (10%), and acute inflammation (8%). Ileal histology findings included increased Peyer patches (44%), normal (44%), acute inflammation (11%), chronic inflammation (3%), eosinophilia (5%), and eosinophilic ileitis (3%). The majority of acute and chronic inflammation was graded as mild. There were no statistically significant associations of histology to gross endoscopy or manometry findings. CONCLUSIONS: Colonic biopsies are obtained in the majority of patients presenting for colonic manometry evaluation with ileal biopsies obtained less frequently. Histopathology findings are noted frequently, but the majority are the result of or did not impact clinical care. There were no associations between abnormal histopathology or abnormal gross endoscopy findings with colonic manometry results.

Pediatric Aerodigestive Medicine: Advancing Collaborative Care for Children With Oropharyngeal Dysphagia.

OBJECTIVES: Aerodigestive disorders encompass various pathological conditions affecting the lungs, upper airway, and gastrointestinal tract in children. While advanced care has primarily occurred in specialty centers, many children first present to general pediatric gastroenterologists with aerodigestive symptoms necessitating awareness of these conditions. At the 2021 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the aerodigestive Special Interest Group held a full-day symposium entitled, Pediatric Aerodigestive Medicine: Advancing Collaborative Care of Children with Aerodigestive Disorders. The symposium aimed to underline the significance of a multidisciplinary approach to achieve better outcomes for these complex patients. METHODS: The symposium brought together leading experts to highlight the growing aerodigestive field, promote new scientific and therapeutic strategies, share the structure and benefits of a multidisciplinary approach in diagnosing common and rare aerodigestive disorders, and foster multidisciplinary discussion of complex cases while highlighting the range of therapeutic and diagnostic options. In this article, we showcase the diagnostic and therapeutic approach to oropharyngeal dysphagia (OPD), one of the most common aerodigestive conditions, emphasizing the role of a collaborative model. CONCLUSIONS: The aerodigestive field has made significant progress and continues to grow due to a unique multidisciplinary, collaborative model of care for these conditions. Despite diagnostic and therapeutic challenges, the multidisciplinary approach has enabled and greatly improved efficient, high-quality, and evidence-based care for patients, including those with OPD.

The Role of Pediatric Gastroenterologists in the Evaluation of Complex Aerodigestive Disorders.

PURPOSE OF REVIEW: Children with aerodigestive disorders frequently have concerns regarding difficulty breathing, swallowing, and growing. In this review, we explored the role of pediatric gastroenterologists in the evaluation of complex aerodigestive disorders and the overall approach to these often-challenging patients. RECENT FINDINGS: Pediatric gastroenterologists evaluate children with aerodigestive concerns ranging from dysphagia and gastroesophageal reflux to complex congenital abnormalities such as esophageal atresia. Diagnostic tools, such as multichannel intraluminal impedance-pH monitoring, are used for diagnosing gastroesophageal reflux and assessing the correlation with symptoms. Endoscopic evaluation, and in some complex cases, with therapeutic dilations may also be performed. Gastrointestinal dysmotility evaluation with manometry studies are also being increasingly utilized. Multidisciplinary aerodigestive programs can provide a coordinated approach to children with complex airway, pulmonary and gastrointestinal tract disorders. A pediatric gastroenterologist's expertise and specialized skills not only offer many diagnostic tools for these complicated medical cases but are also important in long term medical management.

A multi-disciplinary approach to chronic cough in children.

Objectives: (1) To highlight the important causes of chronic and recurrent cough in children. (2) To discuss multidisciplinary approach to management of chronic/recurrent pediatric cough. Methods: Review of scholarly articles, guidelines, expert panels via PubMed and Google Scholar. Conclusion: Chronic cough (CC) in children is mainly attributed to persistent bacterial bronchitis, asthma, nonspecific cough, and gastroesophageal reflux disease (GERD) symptoms. A multi-disciplinary approach is cost-effective and aids with earlier diagnosis and appropriate treatment. Congenital or acquired narrowing of the subglottis is the leading ENT cause for recurrent croup (RC) in children. Laryngeal cleft-type 1 is commonly seen in children with recurrent aspiration and CC. Children are usually referred to pulmonologists for wet cough not responding to treatment. Eosinophilic esophagitis (EoE) and GERD should be considered in the differential diagnosis of CC in children with both respiratory symptoms and failure to thrive.Level of Evidence: 2a.

Gastrointestinal Dysmotility Is a Significant Feature in 2 Siblings With a Novel Inositol 1,4,5-Triphosphate Receptor 1 (ITPR1) Missense Variant.

We present 2 siblings with a novel type 1 inositol 1,4,5-triphosphate receptor (ITPR1) missense variant who exhibit gastrointestinal dysmotility (chronic constipation and gastroparesis). ITPR1 is expressed in the cerebellum and interstitial cells of Cajal. Periodic release of calcium by ITPR1 initiates pacemaker currents, resulting in smooth muscle contraction. ITPR1 mutations are known to be associated with neurologic syndromes, and these variants have not previously been associated with significant gastrointestinal manifestations in humans. Using whole-genome sequencing, in silico prediction software, biopsy samples, and manometry, the identified novel ITPR1 variant is likely pathogenic and may have neurogastroenterology implications.

Pediatric Tracheal Lobular Capillary Hemangioma: A Case Report and Review of the Literature.

Chronic cough is a common complaint in the pediatric population and can have many different etiologies. We present a rare case of a tracheal lobular capillary hemangioma (LCH), also known as pyogenic granuloma, causing chronic cough in a child. In this case, the tracheal LCH was managed successfully with laser ablation. A review of the literature reveals only 2 other reported pediatric cases of tracheal LCH. Laryngoscope, 131:1729-1731, 2021.

Gastrointestinal Hemorrhage: A Manifestation of the Telomere Biology Disorders.

OBJECTIVE: To describe the clinical features, therapeutic interventions, and patient outcomes of gastrointestinal (GI) hemorrhage in individuals with a telomere biology disorder, including dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome, Revesz syndrome, and Coats plus. STUDY DESIGN: Clinical Care Consortium for Telomere Associated Ailments members were invited to contribute data on individuals with telomere biology disorders at their institutions who experienced GI bleeding. Patient demographic, laboratory, imaging, procedural, and treatment information and outcomes were extracted from the medical record. RESULTS: Sixteen patients who experienced GI hemorrhage were identified at 11 centers. Among 14 patients who underwent genetic testing, 8 had mutations in TINF2, 4 had mutations in CTC1 or STN1, and 1 patient each had a mutation in TERC and RTEL1. Ten patients had a history of hematopoietic cell transplantation. The patients with Coats plus and those without Coats plus had similar clinical features and courses. Angiodysplasia of the stomach and/or small bowel was described in 8 of the 12 patients who underwent endoscopy; only 4 had esophageal varices. Various medical interventions were trialed. No single intervention was uniformly associated with cessation of bleeding, although 1 patient had a sustained response to treatment with bevacizumab. Recurrence was common, and the overall long-term outcome for affected patients was poor. CONCLUSIONS: GI bleeding in patients with telomere biology disorders is associated with significant morbidity and with vascular ectasias rather than varices.

Eosinophilic esophagitis with and without airway involvement in children - A comparative analysis.

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic disease characterized by marked eosinophilic infiltration and inflammation of the esophagus eventually leading to esophageal dysfunction. This condition at times may involve the airway leading to breathing difficulties. OBJECTIVE: To compare the course of EoE in patients with or without airway involvement. METHODS: A retrospective chart review was done on patients with a diagnosis of Eosinophilic Esophagitis and that were managed in our Aerodigestive clinic from 2012 to 2018. A total of 121 EoE patients were included in the study. Each patient's disease course was examined for pertinent information including - but not limited to - age at presentation, allergies, endoscopic and pathology results, treatments prescribed, and time to resolution. The data was analyzed for any differences between the airway and non-airway groups for each of these variables. RESULTS: The variables that were analyzed showed no significant difference between patients suffering from EoE with (n = 19) and without (n = 102) airway involvement. However, patients with airway disease trended towards being younger in age at presentation as compared to those without airway symptoms (6.68 years vs. 9.69 years, p = 0.69). Analysis of endoscopic and pathology findings revealed no difference. Similarly, no differences were found between the prescribed treatments. Kaplan-Meier estimates of time to disease remission indicated that 50% of patients had resolution at one year, regardless of airway involvement (p = 0.31). CONCLUSIONS: Our findings indicate that the disease course of patients with EoE does not vary depending on the presence of airway symptoms. Thus, patients with airway symptoms should not be diagnosed or treated any different than those without airway symptoms.

Development of a multidisciplinary colorectal and pelvic health program: Program implementation and clinical impact.

INTRODUCTION: Pediatric patients with complex colorectal and genitourinary conditions often require coordinated multidisciplinary care; however, this coordinated care can be hard to structure and deliver. The purpose of this paper is to review the development and implementation of a multidisciplinary colorectal and pelvic health program, one year after the program's initiation. METHODS: This is an observational retrospective 1-year study (10/1/2017 to 9/30/2018). In fiscal year (FY) 2018, a multidisciplinary colorectal and pelvic health program was initiated. The program development incorporated bimonthly team meetings, educational conferences, and initiation of three clinics: a complex colorectal and genitourinary reconstruction clinic, a bowel management clinic, and a colonic motility clinic. Conditions treated included complex anorectal and cloacal malformations, Hirschsprung disease, and idiopathic constipation. The fiscal year was selected to provide comparative administrative data after program implementation. RESULTS: During the study period, 121 patients underwent comprehensive collaborative evaluation of which 58 (47%) were new to the institution compared to 12 (19%) new patients in the previous year (p < 0.001). In FY 2018, there were 130 procedures performed and 512 collaborative visits with an average of 47 visits per month. This was a 3.4-fold increase in visits compared to FY2017 (171 visits). Of the new patients, 60% (35/58), traveled a median of 181 miles, representing 33 statewide counties, and 4 states compared to a median of 93 miles in the previous fiscal year (p = 0.004). CONCLUSION: The development of a colorectal and pelvic health program is feasible and requires a collaborative approach, necessitating multiple service lines within an institution. Program creation and implementation can result in rapid institutional clinical growth by filling a local and regional need through coordinated multidisciplinary care. LEVEL OF EVIDENCE: IV.

Cost-Effectiveness Analysis of the Surgical Management of Infants Less than One Year of Age with Feeding Difficulties.

BACKGROUND: We compared the cost-effectiveness of the common surgical strategies for the management of infants with feeding difficulty. METHODS: Infants with feeding difficulty undergoing gastrostomy alone (GT), GT and fundoplication, or gastrojejunostomy (GJ) tube were enrolled between 2/2017 and 2/2018. A validated GERD symptom severity questionnaire (GSQ) and visual analog scale (VAS) to assess quality of life (QOL) were administered at baseline, 1 month, and every 6 months. Data collected included demographics, resource utilization, diagnostic studies, and costs. VAS scores were converted to quality adjusted life months (QALMs), and costs per QALM were compared using a decision tree model. RESULTS: Fifty patients initially had a GT alone (71% laparoscopically), and one had a primary GJ. Median age was 4 months (IQR 3-8 months). Median follow-up was 11 months (IQR 5-13 months). Forty-three did well with GT alone. Six (12%) required conversion from GT to GJ tube, and one required a fundoplication. Of those with GT alone, six (14%) improved significantly so that their GT was removed after a mean of 7 ±â€¯3 months. Overall, the median GSQ score improved from 173 at baseline to 18 after 1 year (p < 0.001). VAS scores also improved from 70/100 at baseline to 85/100 at 1 year (p < 0.001). ED visits (59%), readmissions (47%), and clinic visits (88%) cost $58,091, $1,442,139, and $216,739, respectively. GJ tube had significantly higher costs for diagnostic testing compared to GT (median $8768 vs. $1007, p < 0.001). Conversion to GJ tube resulted in costs of $68,241 per QALM gained compared to GT only. CONCLUSIONS: Most patients improved with GT alone without needing GJ tube or fundoplication. GT and GJ tube were associated with improvement in symptoms and QOL. GJ tube patients reported greater gains in QALMS but incurred higher costs. Further analysis of willingness to pay for each additional QALM will help determine the value of care. STUDY AND LEVEL OF EVIDENCE: Cost-effectiveness study, Level II.

Size and Prevalence of Pediatric Aerodigestive Programs in 2017.

OBJECTIVE: Pediatric aerodigestive programs appear to be rapidly proliferating and provide multidisciplinary, coordinated care to complex, medically fragile children. Pediatric subspecialists are considered essential to these programs. This study evaluated the state of these programs in 2017 by surveying their size, composition, prevalence, and the number of patients that they serve. METHODS: The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Aerodigestive Special Interest Group leadership distributed an 11-question survey to the Pediatric Gastroenterology International Listserv. The mean time of the programs' existence, number of half-day clinics, number of procedure days, number of patients evaluated, and the lead primary specialty were evaluated. RESULTS: Thirty-four programs responded. Twenty-five were based in academic centers. Thirty-one programs were located across the United States. The average time of program existence was 5.3 years (standard deviation [SD] = 4.3; range 1-17 years). Approximately 64.7% were started in the past 5 years. Twelve programs were based in the division of gastroenterology. The average number of gastroenterologists serving aerodigestive programs was 2 (SD = 1.1). The mean number of half-day clinic sessions and procedure days were 2.8 (SD = 2.9) and 2.6 (SD = 2), respectively. New and follow-up visits per year in each program averaged 184 (SD = 168; range 10-750). CONCLUSIONS: Pediatric aerodigestive programs are prevalent, proliferating, and serve a large number of complex patients across North America and the world. This survey demonstrated that programs are predominantly based in academic settings. The number of patients cared for by aerodigestive centers varies widely depending on size and age of program.

High-resolution manometric guidance during laparoscopic Heller myotomy: Impact on quality of life and symptom severity for children with achalasia.

BACKGROUND: High-resolution esophageal manometry (HREM) during laparoscopic Heller myotomy (LHM) with fundoplication for achalasia allows tailoring of myotomy length and wrap tightness. The purpose of this study is to quantify long-term postoperative symptom severity and quality of life using validated questionnaires. METHODS: Children ≤18 years with achalasia who previously underwent LHM with intraoperative HREM from 2010 to 2017 were prospectively surveyed. Eckardt Symptom Score (ESS), Achalasia Severity Questionnaire (ASQ), Pediatric Quality of Life Inventory (PedsQL), and Pediatric GERD Symptom and Quality of Life (PGSQ) questionnaires were administered. Scores for historical controls were obtained from prior survey instrument validation studies as comparison. RESULTS: Of 30 eligible patients, 12 (40%) completed the surveys. Mean age at time of surgery was 13 ±â€¯3 years. Assessment was performed at least 10 months after surgery with mean time elapsed of 3.6 ±â€¯2 years. Average premyotomy lower esophageal sphincter (LES) pressure, postmyotomy LES pressure, and postfundoplication LES pressure were 30 ±â€¯10 mmHg, 14 ±â€¯6 mmHg, and 18 ±â€¯9, respectively. ESS (2.3/12), ASQ (39/100 ±â€¯16), PGSQ (symptom: 0.6/4 ±â€¯0.4, school: 0.4/4 ±â€¯0.4), and overall PedsQL (82/100 ±â€¯15) were similar to those of healthy historical controls. CONCLUSION: Children with achalasia undergoing LHM with intraoperative HREM had sustained long-term symptom improvement and quality of life scores comparable to healthy patients. STUDY AND LEVEL OF EVIDENCE: Retrospective, II.