Scott Pentiuk

Dissociation between symptoms and histological severity in pediatric eosinophilic esophagitis

Objectives: The relation between patient symptoms and histological severity of eosinophilic esophagitis (EE) is not known. We created a pediatric EE symptom score (PEESS) and compared the results with histological findings in the esophagus. Patients and Methods: Subjects ages 3 to 18 years with a histological diagnosis of EE or their parent completed a survey rating the frequency and severity of their gastrointestinal symptoms. Scores ranged from 0 to 98. Eosinophil numbers in esophageal biopsy specimens were correlated with the PEESS. Results: A total of 49 subjects completed the PEESS. The symptom score did not correlate with the peak eosinophil count (r2 = 0.079). Newly diagnosed, untreated EE subjects (N = 15) had a mean score of 24.7 ± 16.4 with a modest correlation between the PEESS and the number of eosinophils in the distal esophagus (r2 = 0.37). The mean PEESS score in the 34 treated patients was lower than in untreated patients (15.6 ± 12.9; P = 0.046). The mean score for treated patients in histological remission was the same as for treated patients with active EE, regardless of treatment type. Abdominal pain was the most frequent and severe symptom reported. Among 20 of the 34 subjects (58.8%) in histological remission, 17 (85%) continued to report symptoms with a mean score of 17.4 ± 9.9 (range 1–38). Three children with active histological EE (10%) reported no symptoms. Conclusions: Children with untreated EE had a higher PEESS than treated subjects. Symptoms persisted in 85% of EE patients despite histological resolution and 10% with active EE reported no symptoms. Our data indicate a dissociation between symptoms and histology in pediatric EE.

Efficacy, Dose Reduction, and Resistance to High-Dose Fluticasone in Patients With Eosinophilic Esophagitis

BACKGROUND & AIMS We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms. METHODS We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants age 3-30 years with active EoE. Twenty-eight participants received FP, and 14 participants received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary end point was histologic evidence for CR. Secondary end points were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness. RESULTS After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P = .0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR, and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P = .041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects who did not respond to FP and preliminary evidence for transcripts predictive of FP responsiveness. CONCLUSIONS Daily administration of a high dose of FP induces histologic remission in 65%-77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%-93% of patients who initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance. Clinicaltrials.gov number: NCT00426283.

Eosinophilic Esophagitis in Infants and Toddlers

Feeding refusal is often described in conjunction with the diagnosis of eosinophilic esophagitis (EE) in pediatric patients; however, there are little data regarding the specific clinical manifestations and effective management of this condition in very young children. The aim of this study was to evaluate the presentation of EE in infants and toddlers referred to the Interdisciplinary Feeding Team Clinic of a tertiary referral center and to document responses to treatment. Database matching was performed (from January 2000 to June 2003) to identify infants and toddlers diagnosed with EE who had been referred to the Interdisciplinary Feeding Team Clinic. Endoscopic features required for a diagnosis of EE included esophageal mucosal furrowing, erythema, exudates, or decreased vascular markings. Histologic features of EE were more than 24 eosinophils per high-power field (HPF), thickening of basal cell layer, and papillary (rete peg) lengthening or elongation. All study patients were treated with a combination of proton pump inhibitors (PPI) and fluticasone (swallowed). In addition, elemental diet was instituted in those documented to have a food allergy. Treatment success was defined by an improved oral intake, adequate weight gain, and improved endoscopic and histologic findings at 3–6-month followup. A total of 15 subjects [mean age = 19.9 months (SD = 9.7 months)] who fulfilled the entry criteria during the study period were identified. All 15 children had documented endoscopic improvement and 14/15 children had histologic resolution of EE after therapy. In 13 of the 15 children, this translated to clinical improvement as well.

Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring

Eosinophilic esophagitis (EoE) is diagnosed by symptoms, and at least 15 intraepithelial eosinophils per high power field in an esophageal biopsy. Other pathologic features have not been emphasized. We developed a histology scoring system for esophageal biopsies that evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities were scored using a 4-point scale (0 normal; 3 maximum change). Reliability was demonstrated by strong to moderate agreement among three pathologists who scored biopsies independently (P ≤ 0.008). Several features were often abnormal in 201 biopsies (101 distal, 100 proximal) from 104 subjects (34 untreated, 167 treated). Median grade and stage scores were significantly higher in untreated compared with treated subjects (P ≤ 0.0062). Grade scores for features independent of eosinophil counts were significantly higher in biopsies from untreated compared with treated subjects (basal zone hyperplasia P ≤ 0.024 and DIS P ≤ 0.005), and were strongly correlated (R-square >0.67). Principal components analysis identified three principal components that explained 78.2% of the variation in the features. In logistic regression models, two principal components more closely associated with treatment status than log distal peak eosinophil count (PEC) (R-square 17, area under the curve (AUC) 77.8 vs. R-square 9, AUC 69.8). In summary, the EoE histology scoring system provides a method to objectively assess histologic changes in the esophagus beyond eosinophil number. Importantly, it discriminates treated from untreated patients, uses features commonly found in such biopsies, and is utilizable by pathologists after minimal training. These data provide rationales and a method to evaluate esophageal biopsies for features in addition to PEC.

Development and testing of a CD-ROM program for improving adolescent knowledge of inflammatory bowel disease.

Objective: The aim of this study was to design a theory-based educational program for adolescents with inflammatory bowel disease (IBD) using an interactive multimedia CD-ROM and to test its effectiveness in improving knowledge in IBD. Materials and Methods: Curriculum-based instruction using educational theory and principles was designed for adolescents on an interactive multimedia CD-ROM. Twenty subjects completed summative evaluation of the CD-ROM measuring gain in knowledge about IBD immediately and 9 months after instruction. Results: Subjects found the CD-ROM to be informative, appealing, and easy to use. The mean baseline score of the adolescents on the Crohns and Colitis Knowledge questionnaire was 12.2 (standard deviation 5.14, range 3–24). After an average of 30 minutes of self-directed learning, adolescent subjects increased their posttest score to a mean of 19.8, a gain of 7.6 points over baseline (95% confidence interval 5.2–10.1, P < 0.0001). Knowledge of medications, disease complications, and gastrointestinal structure and function was gained and retained upon retesting at 9 months with a mean Crohns and Colitis Knowledge questionnaire score of 17.5 (standard deviation 3.9, range 12–26), which was still an improvement over the mean pretest knowledge score of 12.2 (P < 0.001). Conclusions: Adolescents with IBD have low baseline knowledge about their disease. A rigorously developed interactive educational tool is now available for instructing adolescent patients about their IBD.

Challenges in meeting fellowship procedural guidelines in pediatric therapeutic endoscopy and liver biopsy

Objective: The aims of this study were to assess the opportunities for therapeutic endoscopy, liver biopsies, and percutaneous endoscopic gastrostomy (PEG) placements available to fellows during a 3-year pediatric gastroenterology fellowship, and to evaluate access to ancillary procedural-training opportunities. Methods: Data were collected from 12 pediatric gastroenterology fellowship programs in the United States. Procedures completed in the years 2009–2011 were queried using CPT codes and endoscopy databases. The maximal opportunity for procedures was based on the total procedures performed by the institution in 3 years divided by the total number of fellows in the program. The centers completed a questionnaire regarding ancillary opportunities for endoscopic training. Results: There is significant variability in pediatric endoscopic training opportunities in specialized gastrointestinal (GI) procedures. Under the 1999 guidelines, no centers were able to meet the thresholds for polypectomy and control of nonvariceal bleeding. The 2013 guidelines allowed the number of programs reaching polypectomy thresholds to increase by 67% but made no difference for control of bleeding despite a decrease in the threshold. Training in PEG placement was not available in 42% of the surveyed centers. Elective ancillary procedural training is offered by 92% of the surveyed centers. Conclusions: Most training programs do not have the volume of therapeutic endoscopy procedures for all of the fellows to meet the training guidelines. Training in therapeutic endoscopy, PEG placement, and liver biopsy in pediatric GI fellowships should be supplemented using all of the possible options including rotations with adult GI providers and hands-on endoscopy courses. A shift toward evaluating competency via quality measures may be more appropriate.

A retrospective review of cyproheptadine for feeding intolerance in children less than three years of age: effects and side effects

Premature infants and those with brain injury often suffer from feeding intolerance and vomiting in the first several years of life. Cyproheptadine is a medication with antihistaminergic, antiserotonergic and anticholinergic effects, thought to increase gastric accommodation. We aimed to retrospectively review our experience using cyproheptadine for feeding intolerance and/or vomiting in children under the age of three.

Calculating and Preparing a Pureed-by-Gastrostomy-Tube (PBGT) Diet for Pediatric Patients With Retching and Gagging Postfundoplication

Children with feeding disorders often require gastrostomy feedings and may experience episodes of retching and gagging. The pureed-by-gastrostomy-tube (PBGT) diet was developed to reduce episodes of retching and gagging, provide a complete source of the child’s nutrition and fluid needs as an alternative to commercialized formulas, and promote oral intake. This article is a follow-up to the authors’ original report. The authors’ intention is to now provide guidelines for other dietitians to calculate and analyze this specialized formula. It also describes feeding guidelines, family education, and ongoing patient follow-up and monitoring.

Impedance probe testing prior to pediatric airway reconstruction.

Objective: This study aimed to determine if preoperative impedance testing changed management and if testing was associated with surgical outcome in patients undergoing airway reconstruction. Methods: Retrospective review of patients who had impedance testing prior to airway reconstruction at a tertiary pediatric hospital from January 2010 to September 2011. Charts were reviewed for demographics, medical/surgical history, impedance testing, and surgical outcomes. Results: Fifty-seven patients were included. Forty-seven (82%) were premature. Forty-seven (82%) had a primary diagnosis of subglottic stenosis. Twenty-six (45%) had prior airway surgery. Thirty-six (63%) had gastroesophageal reflux and 21 (36%) had undergone fundoplication. Patients without fundoplication had a median 46 total reflux, 7 proximal, and 14.5 acidic events compared to a median 5 total reflux, 0 proximal, and 0 acidic events in patients with fundoplication. Impedance testing changed management in 22% (8/36) of nonfundoplication patients and 9.5% (2/21) of fundoplication patients. In unadjusted analysis, fewer fundoplication patients had successful surgery compared to those without (33% vs 67%, P = .01). Prematurity, age at surgery, and previous airway surgery were also important predictors of surgical success. Conclusion: Fewer patients than anticipated had a change in management. Impedance testing was unlikely to change management in fundoplication patients. Patients with fundoplication were less likely to have a successful outcome, suggesting that factors other than reflux influence airway reconstruction outcomes.

Structure and functions of pediatric aerodigestive programs: A consensus statement

We present a multi-disciplinary consensus definition of the aerodigestive care model with specific recommendations regarding associated personnel, infrastructure, research, and outcome measures. Aerodigestive programs provide coordinated interdisciplinary care to pediatric patients with complex congenital or acquired conditions affecting breathing, swallowing, and growth. Although there has been a proliferation of programs, as well as national meetings, interest groups and early research activity, there is, as of yet, no consensus definition of an aerodigestive patient, standardized structure, and functions of an aerodigestive program or a blueprint for research prioritization. The Delphi method was used by a multidisciplinary and multi-institutional panel of aerodigestive providers to obtain consensus on 4 broad content areas related to aerodigestive care: (1) definition of an aerodigestive patient, (2) essential construct and functions of an aerodigestive program, (3) identification of aerodigestive research priorities, and (4) evaluation and recognition of aerodigestive programs and future directions. After 3 iterations of survey, consensus was obtained by either a supermajority of 75% or stability in median ranking on 33 of 36 items. This included a standard definition of an aerodigestive patient, level of participation of specific pediatric disciplines in a program, essential components of the care cycle and functions of the program, feeding and swallowing assessment and therapy, procedural scope and volume, research priorities and outcome measures, certification, coding, and funding. We propose the first consensus definition of the aerodigestive care model with specific recommendations regarding associated personnel, infrastructure, research, and outcome measures. We hope that this may provide an initial framework to further standardize care, develop clinical guidelines, and improve outcomes for aerodigestive patients.