Intestinal Wall Texture Analysis: Finding Fibrosis in Pediatric Patients With Crohn Disease No abstract available

Evaluation of Gastroesophageal Reflux in Children Born With Esophageal Atresia Using pH and Impedance Monitoring Objectives: The aim of the study was to evaluate acid and nonacid gastroesophageal reflux in infants and school-aged children with esophageal atresia (EA) using pH-impedance (pH-MII) monitoring. Methods: Between 2012 and 2017, all 24-hour pH-MII studies performed in infants (≤18 months) and 8-year olds with EA were included. Antiacid therapy was discontinued before study. Exclusion criteria were: isolated tracheoesophageal fistula; esophageal replacement therapy; tube feeding; and monitoring <18 hours. Automatically detected retrograde bolus movements (RBM) were manually reviewed and modified/deleted if necessary. Results: We included 57 children (51% boys; 2% isolated EA; 44% thoracoscopic EA repair): 24 infants (median age 0.6 years) and 33 school-aged children (median age 8.2 years). Of the automatically detected 3313 RBM, 1292 were manually deleted from the tracings: 52% of nonacid RBM and 8% of acid RBM (mainly misinterpreted swallows or 1 event recognized as several events). In infants, median reflux index (RI; pH <4) was 2.6% (abnormal in n = 2), median RBM was 61 (62% nonacid, 58% mixed), and median of the mean BCT was 11 seconds. In older children, median RI was 0.3% (abnormal in n = 4), median RBM was 21 (64% nonacid; 75% mixed), and median of the mean BCT was 13 seconds. Conclusions: Most children with EA off medication have a normal RI, yet experience a significant number of nonacid RBM. After manual revision of the tracings, a high percentage of RBM was deleted. Our data show that automated impedance analysis software needs refinement for use in infants and children with EA and question the need for standard antiacid therapy in these patients.

Multicenter Evaluation of Clinical Efficacy and Safety of Per-oral Endoscopic Myotomy in Children Objectives: Per-oral endoscopic myotomy (POEM) is a recommended treatment modality for achalasia, but there is little published data for its use in children. The objective of the present study was to evaluate whether POEM is clinically effective and safe for children. Methods: International multicenter retrospective study conducted in 14 tertiary centers that included consecutive children who underwent POEM between January 2012 and August 2018. Outcomes, such as clinical response were assessed whenever available. Adverse events and factors associated with clinical failure were also investigated. Results: A total of 117 patients (mean ± SD age: 14.2 ± 3.7 years) underwent POEM for achalasia (type I, n = 36; type II n=66; type III, n=8). Among these, 30 (26%) were pretreated (botulinum injection and/or pneumatic dilatation). Mean ± SD baseline Eckardt score was 7.5 ± 2.0. Clinical success was achieved in 90.6% of cases (95%CI [83.8%;95.2%]) in the intention-to-treat analysis. The mean ± SD Eckardt score post-POEM was 0.9 ± 1.2 (P < 0.001). The mean duration of follow-up time 545 days (range: 100–1612). A total of 7 adverse events occurred (4 mucosotomies, 2 subcutaneous emphysema, 1 esopleural fistula). Gastroesophageal reflux symptoms were seen in 17 patients (15%); missing data for 10 patients (9%). There was a trend towards more frequent clinical failure in achalasia associated with genetic disorders (40% vs 8%, P = 0.069). Conclusions: POEM in pediatric patients appears to be effective and safe, although there was a trend towards more frequent clinical failure achalasia associated with genetic disorders. Further studies are needed to assess the long-term outcomes, especially the consequences of GERD.

Through Thick and Thin: The In Vitro Effects of Thickeners on Infant Feed Viscosity Background: Gastroesophageal reflux disease (GERD) is a common problem in neonates, and current modalities for thickening human milk produce inconsistent outcomes. The objective of this in vitro study is to measure the viscosity effect of different thickening strategies. Methods: We thickened donor human milk (DHM) and formula using various thickeners: starch-based thickeners (SBT; Thick It, rice cereal), and gum-based thickeners (GBT; xanthan gum: Simply Thick, Thicken Up Clear; carob gum: GelMix). We also assessed formula with added starches marketed for reflux, including Similac Spit Up (SSU) and Enfamil AR (EAR). The viscosity of each sample was measured over time using a rotary viscometer. Additional variables, including acidity, temperature, and the addition of human milk fortifier, were tested. Results: Formula can be effectively thickened with all tested thickeners, but the viscosities of thickened formula increase over time. On the other hand, DHM does not effectively thicken with SBT. Autoclaving DHM inactivates digestive enzymes, thus allowing SBT to successfully thicken autoclaved DHM. GBT effectively thickened both DHM and formula but reached higher viscosities than intended based on manufacturer recommendations. Adding acid to xanthan-gum thickened DHM resulted in phase separation and formation of solid precipitant. Conclusions: Current thickening strategies of preterm infant feeding produces highly variable results in final feed viscosity. The unpredictable properties of gum-based thickeners raise questions about their safety profile. Objective measures of liquid viscosity and careful consideration of acidity and time are recommended for adequate comparisons of thickening regimens. Human milk continues to be the most challenging feed type to thicken.

Efficacy and Safety of the Local Application of Mitomycin C to Recurrent Esophageal Strictures in Children Objectives: Research on long-term use of mitomycin C (MC) for recurrent esophageal stenoses is limited. We assessed the long-term efficacy and safety of local application of MC for recurrent esophageal stenoses in children. Methods: This was a retrospective study of 39 patients (17 girls) with a median age of 19.5 months (range: 2.4–196.0) at the time of MC application. The etiologies of stenosis were esophageal atresia (n = 25), caustic ingestion (n = 9), congenital esophageal stenosis (n = 3), and other causes (n = 2). Stenosis was single in 35 (90%) patients and multiple in 4 (10%). Before MC, patients underwent multiple repeated dilations (median: 3 dilations per child [range: 2–26]) over a median period of 7 months (range: 2.6–49.3). Treatment success was defined a priori as a reduction in the number of dilations over the same period from before to after the application of MC. Results: For 26 (67%) patients, the application of MC was considered a success: 102 versus 17 dilatations (P < 0.0001). Sixteen (41%) patients never required additional dilation during the follow-up after MC application (median: 3.1 years [range: 0.6–8.5]). No complication related to MC was observed. Biopsies at the site of MC application were performed at maximal follow-up in 16 patients and revealed no dysplasia. Three factors were associated with success of MC: single stenosis, short stenosis, and esophageal atresia type III. Conclusions: This study is the largest series reported showing that topical application of MC is an efficient and safe treatment for recurrent esophageal stenosis in children.

Texture Analysis of Magnetic Resonance Enterography Contrast Enhancement Can Detect Fibrosis in Crohn Disease Strictures Objective: The aim of the study was to investigate if texture analysis of contrast-enhanced magnetic resonance enterography (MRE) images can determine Crohn disease (CD) stricture histologic type. Materials and Methods: A radiology report database query identified 25 pediatric patients with established CD who underwent MRE followed by bowel resection within 30 days. MRE images were reviewed to identify strictures on enteric phase T1-weighted fat-suppressed images, that were matched with sites of histologic sectioning. Regions of interest were drawn over the bowel wall and texture analysis was performed using TexRAD software (Cambridge, UK), with skewness, mean, entropy and standard deviation parameters assessed. A pathologist reviewed all stricture histology specimens to assess for active mucosal inflammation and mural fibrosis. Multivariate logistic regression and analysis of variance were performed to identify texture features associated with stricture fibrosis. Results: Sixty-four bowel segments from 25 patients (mean age 16 ± 2 years) with imaging-histologic correlation were included. Of note, all strictures included had undergone surgical resection with MRE imaging available within 30 days. The histologic distribution of these bowel segments included 9 segments that showed active inflammation without fibrosis, 23 segments that showed only fibrosis, and 32 mixed segments with concomitant active inflammation and fibrosis. Bivariate regression analysis demonstrated that skewness, standard deviation, entropy, and mean texture analysis features are independently associated with stricture fibrosis. Stepwise logistic regression showed that the combination of mean, skewness, and entropy texture predicted stricture fibrosis with a goodness-of-fit value of 0.995. A combination of threshold values for these 3 texture analysis parameters was able to correctly classify 100% of the strictures in the study cohort for presence (55/55) and absence (9/9) of fibrosis. Conclusions: MRE texture analysis (MRE-TA) texture features can differentiate CD stricture types and accurately detect fibrosis.

Incidence of Paediatric Stricturing Duodenal Crohn Disease: A 19-Year Population-based Cohort Study Objectives: Stricturing duodenal Crohn disease (CD) is a rare but serious presentation of CD causing significant morbidity. We aim to provide the first robust incidence data and case studies on this severe presentation in children. Methods: A regional cohort of prospectively acquired incident cases of paediatric CD diagnosed <16 years of age in South-East Scotland was captured over a 19-year period (1999–2018). A retrospective review was conducted on the medical records of all patients together with a review of the available literature and consensus guidelines. Incidence rates for all CD and for duodenal stricturing CD were calculated. Results: A total of 247 new cases of paediatric CD were diagnosed within the study period. Median age at diagnosis was 12.5 years with 62% male predominance. Overall paediatric CD incidence rate was 5.70/100,000/year with a specific duodenal B2 phenotype disease incidence rate of 0.05/100,000/year; representing 0.8% of incident cases at diagnosis. Two incident cases of stricturing duodenal CD presented with systemic symptoms of weight loss, abdominal pain, anorexia, and lethargy, together with persistent vomiting suggestive of obstruction. Both cases partially responded to intensive medical therapy but eventually required laparoscopic gastroduodenostomy. A detailed literature search confirmed there are no paediatric incidence data, guidelines, or case reports relating to duodenal stricture as either a presentation or complication of CD. Conclusions: Duodenal structuring disease is a rare but serious presentation of CD causing significant morbidity and not currently covered in the paediatric literature or consensus guidelines. Best practice medical and surgical management remain uncertain and require further research.

A Quality Improvement Approach to External Infliximab Infusions in Pediatric Inflammatory Bowel Disease Objectives: We used a quality improvement (QI) approach to improve access and reduce barriers to care by increasing the number of external infliximab infusions at our pediatric inflammatory bowel disease center. Methods: Using an iterative QI strategy, pediatric patients ≥12 years of age with inflammatory bowel disease were offered the opportunity to receive infliximab infusions at home/an external infusion center. They were required to first have >5 infusions at the hospital without any significant infusion reactions. Data were collected and tracked monthly using P-charts. Comparisons between control chart centerlines were analyzed using the Fisher exact test. Results: Fifty-four patients received external infusions, 87% had Crohn disease, 63% boys, average age 17.6 ± 2.9 years, and 89% with private insurance. From September 2016 to January 2018, the percentage of eligible patients receiving external infusions was approximately 7%, increasing to approximately 30% by January 2018. A centerline shift, representing a statistically significant change, occurred in October 2016 and June 2017 (P < 0.001). No serious safety concerns have occurred. Conclusions: Through a multidisciplinary team of stakeholders using QI strategies, we now offer external infusion service options to all appropriate patients as routine practice. Home infusions are a viable option to reduce barriers to care, and our patients did not experience any safety events.

Management of Anti-drug Antibodies to Biologic Medications in Children With Inflammatory Bowel Disease Background: Treatment of pediatric inflammatory bowel disease (IBD) with monoclonal anti- tumor necrosis factor-alpha (TNFα) can result in immunogenicity and formation of anti-drug antibodies (ADAs). ADAs are associated with loss of clinical response and worsening disease progression. Data examining treatment interventions to overcome ADA in pediatric patients with IBD are lacking. Results: Medical records were reviewed from 234 children and adolescents with IBD treated with infliximab or adalimumab who underwent therapeutic drug monitoring (626 tests). All patients who had detectable antibodies were further analyzed. A total 58 patients (24.8%) developed ADA while being treated with infliximab or adalimumab. The incidence of antibody development was 12.9 per 100 person-years of anti-TNF treatment. Twenty-eight patients underwent dose optimization and 54% had undetectable ADA on follow-up monitoring. The mean duration of antibody suppression was 16.8 ± 10.9 months in those who were successfully suppressed with optimization. Patients who switched to a second anti-TNF medication were not more likely to develop antibodies to the second agent. Conclusions: With limited therapies for IBD and the chronicity of the disease, we advocate salvage of the current anti-TNF through dose optimization in pediatric patients with antibody level <10 U/mL.

Using a Steroid-sparing Tool in Paediatric Inflammatory Bowel Disease to Evaluate Steroid Use and Dependency Objectives: The aim of the study was to evaluate the use of steroids within the paediatric inflammatory bowel disease (PIBD) population at a tertiary paediatric centre over a year; to identify cases of steroid dependency; and assess factors associated with steroid excess. Methods: The prevalent PIBD population (May 1, 2017–April 30, 2018) were reviewed. Data were collected retrospectively from patient records and entered into an online steroid assessment tool (modified for paediatrics). Results: A total of 229 patients (181 Crohn disease, 31 ulcerative colitis [UC], and 17 inflammatory bowel disease–unclassified) were included. Of the 229 patients 38 (16.6%) received oral steroids; 12 of 38 (31.6%) receiving >3-month course. Eleven of 38 (28.9%) received >1 steroid course (maximum 2). Of the 229 patients 37 (16.2%) had exclusive enteral nutrition, with 26 of 37 (11.4% total cohort) avoiding steroid use during the study period. Quiescent disease activity had a negative correlation with steroid use (11/127 [8.7%] vs 27/102 [26.5%] P < 0.01), and steroid dependency (3/127 [2.4%] vs 12/102 [11.8%] P < 0.01). Patients with UC were more likely to be steroid dependent (5/31 [16.1%] UC vs 10/198 [5.1%]; P = 0.02); as were network-managed patients (8/11 [72.7%] vs 7/27 [25.9%]; P = 0.01). Fourteen of 15 (93.3%) of steroid-dependent patients had active steroid sparing strategies in place (eg, commencement, switching, or optimization of therapies). Conclusions: We have described rates of steroid use and dependency within our PIBD population. Exclusive enteral nutrition served as a steroid sparing tool in 11.4% of the total cohort. Replication of this study in other paediatric centres would allow comparative analysis.