Medication adherence is a modifiable determinant of successful therapy. Adhering to pharmacologic regimens to treat eosinophilic esophagitis (EoE) can be complicated and burdensome, yet the impact of medication adherence, particularly the self-reported adherence, on EoE activity indices remains understudied. We assessed the association between self-reported adherence to pharmacologic EoE therapy and endoscopic (EoE Endoscopic Reference Score, EREFS; range = 0-9), histologic (peak eosinophil count), and multidimensional Index of Severity for EoE in a prospectively followed pediatric cohort between 2017 and 2024, cross-sectionally and longitudinally, with up to three EGD time points. Self-reported adherence was collected during routine pre-EGD assessment as a percentage of the inter-EGD interval (12-16 weeks). Hierarchical variable clustering was applied to reduce multicollinearity. Our cohort comprised 103 children with an index EGD (EGD 1); 36 and 19 had EGDs at time points 2 and 3, respectively. At EGD 1, children with abnormal esophageal mucosa (EREFS ≥1) had 8% lower self-reported adherence (95% CI: 1-15%; P = 0.02) than those with normal esophageal mucosa (EREFS = 0). Additionally, for each 5-year increase in age, the self-reported adherence decreased by 5% (95% CI: 1-10%; P = 0.05). These trends persisted over time between EGD 1 and EGD 2. Self-reported adherence was not associated with peak eosinophil count, Index of Severity for EoE score, or complexity of pharmacologic regimen. Despite a median adherence of >95%, more than half had active EoE, highlighting the limited reliability of self-report alone. These findings suggest that self-reported adherence aligns with endoscopic, but not with histologic, disease activity and decreases with age, underscoring the need for age-appropriate adherence counseling and objective adherence monitoring in pediatric EoE management.

Background Solid pseudopapillary neoplasms (SPNs) arising in the body or tail of the pancreas can be amenable to laparoscopic distal pancreatectomy with or without concomitant splenectomy. The purpose of this study was to evaluate laparoscopic distal pancreatectomy for SPN using the Warshaw technique as a means to preserve spleens in children. Methods We reviewed our database of SPN patients 19 years and younger (January 2006-December 2023). Five had a laparoscopic Warshaw procedure. Using the volumetric analysis tool in Sectra, a pediatric radiologist calculated preoperative tumor, pancreas, and spleen volumes (including postoperative organ volumes) on computed tomography. Descriptive statistics were performed. Results All five spleens were salvaged, although small infarcts occurred centrally in four patients. Splenic volumes on first imaging after Warshaw averaged 93.9% of preoperative size. Splenic volumes were preserved over time, as the most recent scans averaged 110.6% of the preoperative spleen volume. Collateral flow through the short gastric arteries, inferred from dilation on scans, increased in all patients. Median tumor volume was 85.2 mL, and all SPN were resected with negative margins. No relapse occurred (median follow up: 407 days). Median estimated blood loss was 100 mL, median length of procedure was 4.9 hours, and median inpatient length of stay was 3 days. A multimodal pain regimen, including preoperative TAP blocks, non-opiate, and opiate medications, resulted in a median 81 Morphine Milligram Equivalents (MMEs) administered during the hospital stay. Conclusion Laparoscopic Warshaw for SPN in children appears highly effective at preserving splenic volume without compromising oncologic fidelity or consuming excess inpatient resources.

Eosinophilic esophagitis (EoE) is an immunoinflammatory condition of the esophagus characterized by an intense eosinophilic inflammation. Given its chronic and progressive course, EoE can lead to esophageal remodeling and dysphagia. Current diagnostic methods require repeated endoscopy to rate the severity of esophageal involvement and several biopsies of the esophageal mucosa for histopathologic confirmation of EoE, which can result in misdiagnosis and diagnostic delays. Raman spectroscopy (RS) is an inelastic scattering technique capable of real-time in vivo disease detection. The high wavenumber Raman spectrum contains quantitative information about the biochemical and water content in tissue. Using a pediatric endoscope-compatible fiber-optic RS probe, we acquired in vivo high wavenumber Raman spectra from 44 children with (cases) and without EoE (controls). Spectral unmixing revealed that children with active EoE had significantly altered carbohydrate, nucleic acid, collagen, non-collagen protein, lipid, and water signals allowing for differentiation from non-EoE controls and children with inactive EoE (treatment responders). These findings were verified by ex vivo analysis of esophageal biopsies with stimulated Raman scattering (SRS) microscopy, Raman microspectroscopy, and histochemical staining, which revealed significant decreases in epithelial carbohydrate content and increases in nucleic acid content in active EoE. Ex vivo SRS and RS measurements of full-thickness esophageal tissue revealed that subepithelial layers were the source of lipid and protein alterations observed in vivo. This study underscores the potential of high wavenumber RS for real-time in vivo detection of EoE and its activity status while offering comprehensive insights into the disease-specific esophageal biochemical changes validated through complementary techniques.

BACKGROUND:Choledochal cysts pose risk for biliary carcinoma, although age-related progression of biliary epithelial transformation remains uncharacterized. This study aimed to elucidate the carcinoma sequence within choledochal cysts across all patient ages to inform cancer risk and screening. METHODS:Patients treated either for choledochal cysts or biliary carcinoma at 1 institution (1988-2023) were analyzed. Choledochal cyst pathology was reviewed for biliary epithelial changes, whereas patients with biliary carcinoma were assessed for history of choledochal cysts. Descriptive statistics and logistic regression of age at epithelial change were performed. RESULTS:Among 130 patients with choledochal cysts, median age at resection was 12 years, female patients predominated (73%), and Asian race was 2.5-fold increased. Patients commonly presented with biliary obstruction, pancreatitis, and type I choledochal cysts. Cyst pathology revealed chronic inflammation (56.1%) and progressive epithelial transformation (6.9%): 3 metaplasia, 1 hyperplasia, 3 dysplasia, and 3 synchronous biliary carcinoma. Logistic regression showed positive association between increasing age at excision and progressive epithelial transformation (P = .038). One 6-year-old patient with choledochal cysts developed metachronous biliary carcinoma at age 37 years. Among 886 nonampullary patients with biliary carcinoma, 8 (0.9%) had choledochal cysts: 7 synchronous and the same metachronous. Resection of choledochal cysts after age 17 years showed increased odds for epithelial transformation (odds ratio, 15.0; P = .0093). Cumulatively, median age (years) increased from premalignant biliary epithelial transformation (34 [16-35]), to biliary carcinoma with choledochal cysts (51 [37-78]), to biliary carcinoma without choledochal cysts (65 [56-72]; P < .001). CONCLUSION:These data infer sequential epithelial transformation to biliary carcinoma correlating with increasing age at resection of choledochal cysts. Coupled with 1 case of metachronous biliary carcinoma, this study underscores the need to screen patients with previous excision of choledochal cysts for cancer beginning at age 30 years.

CONTEXT.—:Frozen section (FS) evaluation of pediatric bone and soft tissue (BST) lesions is infrequently encountered and may pose considerable diagnostic challenges. Limited data exist about the accuracy and related diagnostic difficulties. OBJECTIVE.—:To identify and analyze discrepancies between the FS diagnosis and final diagnosis in order to increase the awareness of common diagnostic pitfalls in FS evaluation of pediatric BST lesions. DESIGN.—:We retrospectively reviewed 595 consecutive FSs of pediatric BST lesions from 373 patients and analyzed the accuracy and causes for interpretation errors. RESULTS.—:Discrepant diagnoses were found in 23 of 595 FSs (3.9%). Discrepancy rates were slightly higher in benign soft tissue lesions and FSs requested for diagnosis/adequacy, although no statistically significant difference was observed. Pathologist misinterpretation contributed to discrepancy in 17 of 23 FSs (73.9%), which were classified into 6 patterns of error. For margin, 3 patterns were found: normal hematopoietic elements versus malignant cells in Ewing sarcoma bone marrow margin (n = 3), prominent sinonasal vasculature and stroma versus sinonasal tract angiofibroma (n = 3), and atrophic skeletal muscles versus malignant cells in rhabdomyosarcoma and Ewing sarcoma (n = 2). For diagnosis, another 3 patterns were identified: misclassification of benign bone tumors (n = 5), misclassification of benign spindle neoplasms (n = 2), and vascular malformation versus normal tissue (n = 2). CONCLUSIONS.—:FS is a valuable tool for guiding surgical management of pediatric BST lesions, which can be challenging entities and represent significant diagnostic pitfalls. Awareness of these FS pitfalls may help in further increasing diagnostic accuracy.

Context.-Frozen section (FS) evaluation of pediatric bone and soft tissue (BST) lesions is infrequently encountered and may pose considerable diagnostic challenges. Limited data exist about the accuracy and related diagnostic difficulties. Objective.-To identify and analyze discrepancies between the FS diagnosis and final diagnosis in order to increase the awareness of common diagnostic pitfalls in FS evaluation of pediatric BST lesions. Design.-We retrospectively reviewed 595 consecutive FSs of pediatric BST lesions from 373 patients and analyzed the accuracy and causes for interpretation errors. Results.-Discrepant diagnoses were found in 23 of 595 FSs (3.9%). Discrepancy rates were slightly higher in benign soft tissue lesions and FSs requested for diagnosis/ adequacy, although no statistically significant difference was observed. Pathologist misinterpretation contributed to discrepancy in 17 of 23 FSs (73.9%), which were classified into 6 patterns of error. For margin, 3 patterns were found: normal hematopoietic elements versus malignant cells in Ewing sarcoma bone marrow margin (n = 3), prominent sinonasal vasculature and stroma versus sinonasal tract angiofibroma (n = 3), and atrophic skeletal muscles versus malignant cells in rhabdomyosarcoma and Ewing sarcoma (n = 2). For diagnosis, another 3 patterns were identified: misclassification of benign bone tumors (n = 5), misclassification of benign spindle neoplasms (n = 2), and vascular malformation versus normal tissue (n = 2). Conclusions.-FS is a valuable tool for guiding surgical management of pediatric BST lesions, which can be challenging entities and represent significant diagnostic pitfalls. Awareness of these FS pitfalls may help in further increasing diagnostic accuracy.

BACKGROUND:A combination of proton-pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non-responders (EoE-PPI-TSnr; n = 7) and responders (EoE-PPI-TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics. METHODS:Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression. RESULTS:In all, 3164 upregulated and 3154 downregulated genes distinguished EoE-PPI-TSnr from EoE-PPI-TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE-PPI-TSnr. There was a 56% overlap in dysregulated genes between EoE-PPI-TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic-erythroid progenitors, and T helper type 1 cells were significantly higher in EoE-PPI-TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE-PPI-TSnr and correlated with the key pathways. CONCLUSION:Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies.

Objective: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. Background: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. Methods: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. Results: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P =0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P =0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P =0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. Conclusions: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

Eosinophilic Esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease, characterized by symptoms related to esophageal dysfunction and histological evidence of eosinophil-dominant inflammation. Owing to the intricate microscopic representation of EoE in imaging, current methodologies which depend on manual identification are not only labor-intensive but also prone to inaccuracies. In this study, we develop an open-source toolkit, named Open-EoE, to perform end-to-end whole slide image (WSI) level eosinophil (Eos) detection using one line of command via Docker. Specifically, the toolkit supports three state-of-the-art deep learning-based object detection models. Furthermore, Open-EoE further optimizes the performance by implementing an ensemble learning strategy, and enhancing the precision and reliability of our results. The experimental results demonstrated that the Open-EoE toolkit can efficiently detect Eos on a testing set with 289 WSIs. At the widely accepted threshold of >= 15 Eos per high power field (HPF) for diagnosing EoE, the Open-EoE achieved an accuracy of 91%, showing decent consistency with pathologist evaluations. This suggests a promising avenue for integrating machine learning methodologies into the diagnostic process for EoE. The docker and source code has been made publicly available at https://github.com/hrlblab/Open-EoE.

INTRODUCTION: Biochemical alterations in the esophagus of patients with eosinophilic esophagitis (EoE) are poorly understood. We used Raman spectroscopy through a pediatric endoscope to identify key Raman features reflective of the esophageal biochemical composition to differentiate between children with EoE from non-EoE controls and between children with active (aEoE) and inactive EoE (iEoE). METHODS: Spectral measurements were obtained using a customized pediatric endoscope-compatible fiber-optic Raman probe in real time during an esophagogastroduodenoscopy. Chemometric analysis was performed to identify key Raman features associated with EoE. Pearson correlation analysis was used to assess relationship between the key Raman features and EoE activity indices. Their diagnostic utility was ascertained using the receiver operator characteristic curve analysis. RESULTS: Forty-three children were included in the study (EoE = 32 [74%] and non-EoE control = 11 [26%]; aEoE = 20 [63%] and iEoE = 12 [37%]). Raman intensities assigned to lipids, proteins, and glycogen:protein ratio accurately distinguished children with EoE from those without EoE and aEoE from iEoE. They significantly correlated with EoE activity indices. The Raman peak ratio for lipids had 90.6% sensitivity, 100% specificity, and an area under the curve of 0.95 to differentiate children with EoE from non-EoE controls. The glycogen:protein ratio had 70% sensitivity, 91.7% specificity, and an area under the curve of 0.75 to distinguish children with aEoE from iEoE. DISCUSSION: Real-time intraendoscopy Raman spectroscopy is an effective method for identifying spectral markers reflective of the esophageal biochemical composition in children with EoE. This technique may aid in the diagnosis and monitoring of EoE and help to elucidate EoE pathogenesis.

Eosinophilic esophagitis (EoE) is a chronic and relapsing disease characterized by esophageal inflammation. Symptoms of EoE include difficulty swallowing, food impaction, and chest pain which significantly impact the quality of life, resulting in nutritional impairments, social limitations, and psychological distress. The diagnosis of EoE is typically performed with a threshold (15 to 20) of eosinophils (Eos) per high-power field (HPF). Since the current counting process of Eos is a resource-intensive process for human pathologists, automatic methods are desired. Circle representation has been shown as a more precise, yet less complicated, representation for automatic instance cell segmentation such as CircleSnake approach. However, the CircleSnake was designed as a single-label model, which is not able to deal with multi-label scenarios. In this paper, we propose the multi-label CircleSnake model for instance segmentation on Eos. It extends the original CircleSnake model from a single-label design to a multi-label model, allowing segmentation of multiple object types. Experimental results illustrate the CircleSnake model's superiority over the traditional Mask R-CNN model and DeepSnake model in terms of average precision (AP) in identifying and segmenting eosinophils, thereby enabling enhanced characterization of EoE. This automated approach holds promise for streamlining the assessment process and improving diagnostic accuracy in EoE analysis. The source code has been made publicly available at https://github.com/yilinliu610730/EoE.

Introduction Traction-induced growth (Foker procedure) is a method for esophageal lengthening when primary anastomosis is not feasible in long-gap type A esophageal atresia (EA). We sought to identify the source of esophageal vascularization after thoracoscopic internal traction by analyzing markers of angiogenesis in resected esophageal pouch tips. Case Report A child with Type A EA underwent esophageal lengthening with internal traction. In addition to EA, the patient also had trisomy 21, duodenal atresia, intestinal malrotation, and congenital heart disease. Operations for EA included thoracoscopic esophageal traction system placement at 7 months of age, and 5 subsequent tightening procedures over the following month. Baseline esophageal gap length was 5.5 cm without tension and 4 cm at maximal tension. Gap length was 3.6 cm, 1.4 cm, 1.3 cm, 7 mm, and 5 mm after each tightening procedure, respectively. Final esophageal anastomosis was done at 8 months of age. At the time of the anastomosis, angiogenic vessels were grossly visible at the ends of each esophageal pouch and indocyanine green fluorescence angiography demonstrated vascularization. Resected samples of the esophageal pouches were analyzed with immunohistochemistry for expression of ERG, a marker of angiogenesis. The patient who underwent traction demonstrated increased submucosal ERG expression (average 6.30% cells) compared to 5 control patients who did not require traction-based lengthening to achieve anastomosis (average 1.34% cells). Conclusion Thoracoscopic traction with serial tightening achieves adequate growth to restore esophageal continuity in patients with long-gap EA. Our findings suggest that anastomotic blood supply relies upon submucosal angiogenesis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by an intense infiltration of eosinophils into the esophageal epithelium. When not adequately controlled, eosinophilic inflammation can lead to changes in components of the extracellular matrix (ECM) of the lamina propria. Particularly, alterations to the collagen fiber matrix can lead to lamina propria fibrosis (LPF), which plays an important role in the fibrostenotic complications of EoE. Current approaches to assess LPF in EoE are prone to inter-observer inconsistencies and provide limited insight into the structural remodeling of the ECM. An objective approach to quantify LPF can eliminate inter-observer inconsistencies and provide novel insights into the fibrotic transformation of the lamina propria in EoE. Second harmonic generation (SHG) microscopy is a powerful modality for objectively quantifying disease associated alterations in ECM collagen structure that is finding increasing use for clinical research. We used SHG with morphometric analysis (SHG-MA) to characterize lamina propria collagen fibers and ECM porosity in esophageal biopsies collected from children with active EoE (n = 11), inactive EoE (n = 11), and non-EoE (n = 11). The collagen fiber width quantified by SHG-MA correlated positively with peak eosinophil count (r = 0.65, p < 0.005) and histopathologist scoring of LPF (r = 0.52, p < 0.005) in the esophageal biopsies. Patients with active EoE had a significant enlargement of ECM pores compared to inactive EoE and non-EoE (p < 0.005), with the mean pore area correlating positively with EoE activity (r = 0.76, p < 0.005) and LPF severity (r = 0.65, p < 0.005). These results indicate that SHG-MA can be utilized to objectively characterize and provide novel insights into lamina propria ECM structural remodeling in children with EoE, which could aid in monitoring disease progression.