High-resolution esophageal manometry in pediatrics: Effect of esophageal length on diagnostic measures.

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.

Oesophageal atresia.

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.

Clinical Management of Pediatric Achalasia: A Survey of Current Practice.

OBJECTIVES: Pediatric achalasia is a rare neurodegenerative disorder of the esophagus that requires treatment. Different diagnostic and treatment modalities are available, but there are no data that show how children can best be diagnosed and treated. We aimed to identify current practices regarding the diagnostic and therapeutic approach toward children with achalasia. METHODS: Information on the current practice regarding the management of pediatric achalasia was collected by an online-based survey sent to members of the European and North American Societies for Pediatric Gastroenterology Hepatology and Nutrition involved in pediatric achalasia care. RESULTS: The survey was completed by 38 centers from 24 countries. Within these centers, 108 children were diagnosed with achalasia in the last year (median 2, range 0-15). Achalasia was primarily managed by a pediatric gastroenterologist (76%) and involved a multidisciplinary team in 84% of centers, also including a surgeon (87%), radiologist (61%), dietician (37%), speech pathologist (8%), and psychologist (5%). Medical history taking and physical examination were considered most important to establish the diagnosis (50%), followed by (a combination of) manometry (45%) or contrast swallow (21%). Treatment of first choice was Heller myotomy (58%), followed by pneumatic dilation (46%) and peroral endoscopic myotomy (29%). CONCLUSION: This study shows a great heterogeneity in the management of pediatric achalasia amongst different centers worldwide. These findings stress the need for well-designed intervention trials in children with achalasia. Given the rarity of this disease, we recommend that achalasia care should be managed in centers with access to appropriate diagnostic and treatment modalities.

Clinical management of pediatric achalasia.

INTRODUCTION: Achalasia is a rare esophageal motility disorder. Much of the literature is based on the adult population. In adults, guidance of therapeutic approach by manometric findings has led to improvement in patient outcome. Promising results have been achieved with novel therapies such as PerOral Endoscopic Myotomy (POEM). Areas covered: In this review, we provide an overview of the novel diagnostic and therapeutic tools for achalasia management and in what way they will relate to the future management of pediatric achalasia. We performed a PubMed and EMBASE search of English literature on achalasia using the keywords 'children', 'achalasia', 'pneumatic dilation', 'myotomy' and 'POEM'. Cohort studies < 10 cases and studies describing patients ≥ 20 years were excluded. Data regarding patient characteristics, treatment outcome and adverse events were extracted and presented descriptively, or pooled when possible. Expert commentary: Available data report that pneumatic dilation and laparoscopic Heller's myotomy are effective in children, with certain studies suggesting lower success rates in pneumatic dilation. POEM is increasingly used in the pediatric setting with promising short-term results. Gastro-esophageal reflux disease (GERD) may occur post-achalasia intervention due to disruption of the LES and therefore requires diligent follow-up, especially in children treated with POEM.

Pediatric Gastroesophageal Reflux Disease: Systematic Review on Prognosis and Prognostic Factors.

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.

Variations in Definitions and Outcome Measures in Gastroesophageal Reflux Disease: A Systematic Review.

CONTEXT: Gastroesophageal reflux (GER) is defined as GER disease (GERD) when it leads to troublesome symptoms and/or complications. We hypothesized that definitions and outcome measures in randomized controlled trials (RCTs) on pediatric GERD would be heterogeneous. OBJECTIVES: Systematically assess definitions and outcome measures in RCTs in this population. DATA SOURCES: Data were obtained through Cochrane, Embase, Medline, and Pubmed databases. STUDY SELECTION: We selected English-written therapeutic RCTs concerning GERD in children 0 to 18 years old. DATA EXTRACTION: Data were tabulated and presented descriptively. Each individual parameter or set of parameters with unique criteria for interpretation was considered a single definition for GER(D). Quality was assessed by using the Delphi score. RESULTS: A total of 2410 unique articles were found; 46 articles were included. Twenty-six (57%) studies defined GER by using 25 different definitions and investigated 25 different interventions. GERD was defined in 21 (46%) studies, all using a unique definition and investigating a total of 23 interventions. Respectively 87 and 61 different primary outcome measures were reported by the studies in GER and GERD. Eight (17%) studies did not report on side effects. Of the remaining 38 (83%) studies that did report on side effects, 18 (47%) included this as predefined outcome measure of which 4 (22%) as a primary outcome measure. Sixteen studies (35%) were of good methodological quality. LIMITATIONS: Only English-written studies were included. CONCLUSIONS: Inconsistency and heterogeneity exist in definitions and outcome measures used in RCTs on pediatric GER and GERD; therefore, we recommend the development of a core outcome set.

Reliability of the reflux finding score for infants in flexible versus rigid laryngoscopy.

OBJECTIVES: The Reflux Finding Score for Infants (RFS-I) was developed to assess signs of laryngopharyngeal reflux (LPR) in infants. With flexible laryngoscopy, moderate inter- and highly variable intraobserver reliability was found. We hypothesized that the use of rigid laryngoscopy would increase reliability and therefore evaluated the reliability of the RFS-I for flexible versus rigid laryngoscopy in infants. METHODS: We established a set of videos of consecutively performed flexible and rigid laryngoscopies in infants. The RFS-I was scored twice by 4 otorhinolaryngologists, 2 otorhinolaryngology fellows, and 2 inexperienced observers. Cohen's and Fleiss' kappas (k) were calculated for categorical data and the intraclass correlation coefficient (ICC) was calculated for ordinal data. RESULTS: The study set consisted of laryngoscopic videos of 30 infants (median age 7.5 (0-19.8) months). Overall interobserver reliability of the RFS-I was moderate for both flexible (ICC = 0.60, 95% CI 0.44-0.76) and rigid (ICC = 0.42, 95% CI 0.26-0.62) laryngoscopy. There were no significant differences in reliability of overall RFS-I scores and individual RFS-I items for flexible versus rigid laryngoscopy. Intraobserver reliability of the total RFS-I score ranged from fair to excellent for both flexible (ICC = 0.33-0.93) and rigid (ICC = 0.39-0.86) laryngoscopies. Comparing RFS-I results for flexible versus rigid laryngoscopy per observer, reliability ranged from no to substantial (k = -0.16-0.63, mean k = 0.22), with an observed agreement of 0.08-0.35. CONCLUSION: Reliability of the RFS-I was moderate and did not differ between flexible and rigid laryngoscopies. The RFS-I is not suitable to detect signs or to guide treatment of LPR in infants, neither with flexible nor with rigid laryngoscopy.

Development of the reflux finding score for infants and its observer agreement.

OBJECTIVE: It is hypothesized that laryngeal edema is caused by laryngopharyngeal reflux (LPR) (ie, gastroesophageal reflux extending into the larynx and pharynx). The validated reflux finding score (RFS) assesses LPR disease in adults. We, therefore, aimed to develop an adapted RFS for infants (RFS-I) and assess its observer agreement. STUDY DESIGN: Visibility of laryngeal anatomic landmarks was assessed by determining observer agreement. The RFS-I was developed based on the RFS, the found observer agreement, and expert opinion. An educational tutorial was developed which was presented to 3 pediatric otorhinolaryngologists, 2 otorhinolaryngologists, and 2 gastroenterology fellows. They then scored videos of flexible laryngoscopy procedures of infants who were either diagnosed with or specifically without laryngeal edema. RESULTS: In total, 52 infants were included with a median age of 19.5 (0-70) weeks, with 12 and 40 infants, respectively, for the assessment of the laryngeal anatomic landmarks and the assessment of the RFS-I. Overall interobserver agreement of the RFS-I was moderate (intraclass correlation coefficient = 0.45). Intraobserver agreement ranged from moderate to excellent agreement (intraclass correlation coefficient = 0.50-0.87). CONCLUSION: A standardized scoring instrument was developed for the diagnosis of LPR disease using flexible laryngoscopy. Using this tool, only moderate interobserver agreement was reached with a highly variable intraobserver agreement. Because a valid scoring system for flexible laryngoscopy is lacking up until now, the RFS-I and flexible laryngoscopy should not be used solely to clinically assess LPR related findings of the larynx, nor to guide treatment.

Upper gastrointestinal motility: prenatal development and problems in infancy.

Deglutition, or swallowing, refers to the process of propulsion of a food bolus from the mouth into the stomach and involves the highly coordinated interplay of swallowing and breathing. At 34 weeks gestational age most neonates are capable of successful oral feeding if born at this time; however, the maturation of respiration is still in progress at this stage. Infants can experience congenital and developmental pharyngeal and/or gastrointestinal motility disorders, which might manifest clinically as gastro-oesophageal reflux (GER) symptoms, feeding difficulties and/or refusal, choking episodes and airway changes secondary to micro or overt aspiration. These problems might lead to impaired nutritional intake and failure to thrive. These gastrointestinal motility disorders are mostly classified according to the phase of swallowing in which they occur, that is, the oral preparatory, oral, pharyngeal and oesophageal phases. GER is a common phenomenon in infancy and is referred to as GERD when it causes troublesome complications. GER is predominantly caused by transient relaxation of the lower oesophageal sphincter. In oesophageal atresia, oesophageal motility disorders develop in almost all patients after surgery; however, a congenital origin of disordered motility has also been proposed. This Review highlights the prenatal development of upper gastrointestinal motility and describes the most common motility disorders that occur in early infancy.

Low rates of adherence for tumor necrosis factor-α inhibitors in Crohn's disease and rheumatoid arthritis: results of a systematic review.

AIM: To investigate adherence rates in tumor necrosis factor-α (TNF-α)-inhibitors in Crohn's disease (CD) and rheumatoid arthritis (RA) by systematic review of medical literature. METHODS: A structured search of PubMed between 2001 and 2011 was conducted to identify publications that assessed treatment with TNF-α inhibitors providing data about adherence in CD and RA. Therapeutic agents of interest where adalimumab, infliximab and etanercept, since these are most commonly used for both diseases. Studies assessing only drug survival or continuation rates were excluded. Data describing adherence with TNF-α inhibitors were extracted for each selected study. Given the large variation between definitions of measurement of adherence, the definitions as used by the authors where used in our calculations. Data were tabulated and also presented descriptively. Sample size-weighted pooled proportions of patients adherent to therapy and their 95%CI were calculated. To compare adherence between infliximab, adalimumab and etanercept, the adherence rates where graphed alongside two axes. Possible determinants of adherence were extracted from the selected studies and tabulated using the presented OR. RESULTS: Three studies on CD and three on RA were identified, involving a total of 8147 patients (953 CD and 7194 RA). We identified considerable variation in the definitions and methodologies of measuring adherence between studies. The calculated overall sample size-weighted pooled proportion for adherence to TNF-α inhibitors in CD was 70% (95%CI: 67%-73%) and 59% in RA (95%CI: 58%-60%). In CD the adherence rate for infliximab (72%) was highercompared to adalimumab (55%), with a relative risk of 1.61 (95%CI: 1.27-2.03), whereas in RA adherence for adalimumab (67%) was higher compared to both infliximab (48%) and etanercept (59%), with a relative risk of 1.41 (95%CI: 1.3-1.52) and 1.13 (95%CI: 1.10-1.18) respectively. In comparative studies in RA adherence to infliximab was better than etanercept and etanercept did better than adalimumab. In three studies, the most consistent factor associated with lower adherence was female gender. Results for age, immunomodulator use and prior TNF-α inhibitors use were conflicting. CONCLUSION: One-third of both CD and RA patients treated with TNF-α inhibitors are non-adherent. Female gender was consistently identified as a negative determinant of adherence.