Anorectal Manometry in Pediatric Colorectal Surgical Care.

BACKGROUND: Pediatric colorectal specialists care for patients with a variety of defecation disorders. Anorectal (AR) manometry testing is a valuable tool in the diagnosis and management of these children. This paper provides a summary of AR manometry techniques and applications as well as a review of AR manometry findings in pediatric patients with severe defecation disorders referred to a pediatric colorectal center. This is the first study describing multi-year experience using a portable AR manometry device in pediatric patients. METHODS: An electronic medical record review was performed (1/2018 to 12/2023) of pediatric patients with defecation disorders who had AR manometry testing. Demographics, diagnostic findings, and outcomes are described. KEY RESULTS: A total of 297 unique patients (56.9% male, n = 169) had AR manometry testing. Of these, 72% (n = 188) had dyssynergic defecation patterns, of which 67.6% (n = 127) had fecal soiling prior to treatment. Pelvic rehabilitation (PR) was administered to 35.4% (n = 105) of all patients. A total of 79.5% (n = 58) of the 73 patients that had fecal soiling at initial presentation and completed PR with physical therapy and a bowel management program were continent after therapy. AR manometry was well tolerated, with no major complications. CONCLUSIONS: AR manometry is a simple test that can help guide the management of pediatric colorectal surgical patients with defecation disorders. As a secondary finding, PR is a useful treatment for patients with dyssynergic stooling.

Healthcare Burden and Cost in Children with Anorectal Malformation During the First 5 Years of Life.

OBJECTIVE: To identify cumulative 5-year healthcare costs and healthcare days in children with anorectal malformation (ARM) and to compare the cumulative 5-year healthcare costs and healthcare days in children with ARM with 3 control cohorts: healthy, premature, and congenital heart disease (CHD). STUDY DESIGN: We performed a retrospective case-control study using the Truven MarketScan database of commercial claims encounters between 2008 and 2017. The ARM, CHD, and premature cohorts were identified using a targeted list of International Classification of Diseases 9th or 10th Revision diagnosis and Current Procedural Terminology codes. The healthy cohort included patients without ARM, preterm birth, or CHD. RESULTS: We identified 664 children with ARM, 3356 children with heart disease, 63 190 children who were born preterm, and 2947 healthy patients. At 5 years, the total healthcare costs of children with ARM ($273K, 95% CI $168K-$378K) were similar to the premature cohort ($246K, 95% CI $237K-$255K) and lower than the CHD cohort ($466K, 95% CI $401K-$530K, P < .001). Total healthcare days were similar in children with ARM (158 days, 95% CI 117-198) and prematurity (141 days, 95% CI 137-144) but lower than CHD (223 days, 95% CI 197-250, P = .02). In ARM, outpatient care (126 days, 95% CI 93-159) represented the largest contribution to total healthcare days. CONCLUSIONS: Children with ARM accumulate similar healthcare costs to children with prematurity and comparable healthcare days to children with CHD and prematurity in the first 5 years of life. Outpatient care represents the majority of healthcare days in children with ARM, identifying this as a target for quality improvement and demonstrating the long-term impact of this condition.

17ß-Estradiol protects the esophageal epithelium from IL-13-induced barrier dysfunction and remodeling.

BACKGROUND: The incidence of eosinophilic esophagitis (EoE) is greater in male than female subjects, and the underlying molecular basis for this sex bias remains unclear. OBJECTIVE: We sought to delineate the contribution of the sex hormone estrogen to the EoE phenotype and esophageal epithelial barrier function and remodeling. METHODS: We performed demographic and incidence analyses of EoE in male and female subjects from a single-center pediatric cohort. Estrogen-responsive gene expression analyses and estrogen receptor (ESR) immunofluorescence staining of esophageal biopsy specimens from patients with EoE and control subjects were performed. The effect of 17ß-estradiol (E2) on IL-13-induced signaling pathways, gene expression, and esophageal epithelial architecture and barrier function in a primary human esophageal keratinocyte cell (EPC2) culture system (EPC2-air-liquid interface) was examined. RESULTS: We observed a male predominance in patients with EoE. Analyses of RNA sequencing data sets revealed a significant dysregulation of the estrogen-responsive gene network and expression of ESR1 and ESR2 in esophageal biopsy specimens from patients with EoE compared with control subjects. IL-13 stimulation of EPC2-air-liquid interface cells led to altered cellular architecture with induced dilation of intercellular spaces and barrier dysfunction. Pretreatment of EPC2s with E2 prior to IL-13 exposure abrogated IL-13-induced architectural changes and esophageal barrier dysfunction. Mechanistically, E2-protective effects were dependent on ESR2 and associated with diminishing of IL-13-induced tyrosine kinase 2 and signal transducer and activator of transcription 6 phosphorylation and EoE-dysregulated gene expression. CONCLUSIONS: Estrogen-responsive genes are modified in patients with EoE compared with control subjects. E2 attenuated IL-13-induced architectural changes and esophageal epithelial barrier dysfunction through inhibition of the IL-13/tyrosine kinase 2/signal transducer and activator of transcription 6 pathway via ESR2-dependent process. Estrogen hormone signaling may protect against development of EoE in female subjects.

Solute carrier family 9, subfamily A, member 3 (SLC9A3)/sodium-hydrogen exchanger member 3 (NHE3) dysregulation and dilated intercellular spaces in patients with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by histopathologic modifications of esophageal tissue, including eosinophil-rich inflammation, basal zone hyperplasia, and dilated intercellular spaces (DIS). The underlying molecular processes that drive the histopathologic features of EoE remain largely unexplored. OBJECTIVE: We sought to investigate the involvement of solute carrier family 9, subfamily A, member 3 (SLC9A3) in esophageal epithelial intracellular pH (pHi) and DIS formation and the histopathologic features of EoE. METHODS: We examined expression of esophageal epithelial gene networks associated with regulation of pHi in the EoE transcriptome of primary esophageal epithelial cells and an in vitro esophageal epithelial 3-dimensional model system (EPC2-ALI). Molecular and cellular analyses and ion transport assays were used to evaluate the expression and function of SLC9A3. RESULTS: We identified altered expression of gene networks associated with regulation of pHi and acid-protective mechanisms in esophageal biopsy specimens from pediatric patients with EoE (healthy subjects, n = 6; patients with EoE, n = 10). The most dysregulated gene central to regulating pHi was SLC9A3. SLC9A3 expression was increased within the basal layer of esophageal biopsy specimens from patients with EoE, and expression positively correlated with disease severity (eosinophils/high-power field) and DIS (healthy subjects, n = 10; patients with EoE, n = 10). Analyses of esophageal epithelial cells revealed IL-13-induced, signal transducer and activator of transcription 6-dependent SLC9A3 expression and Na+-dependent proton secretion and that SLC9A3 activity correlated positively with DIS formation. Finally, we showed that IL-13-mediated, Na+-dependent proton secretion was the primary intracellular acid-protective mechanism within the esophageal epithelium and that blockade of SLC9A3 transport abrogated IL-13-induced DIS formation. CONCLUSIONS: SLC9A3 plays a functional role in DIS formation, and pharmacologic interventions targeting SLC9A3 function may suppress the histopathologic manifestations in patients with EoE.