A Quantitative Assessment of Mucosal Eosinophils in the Gastrointestinal Tract of Children Without Detectable Organic Disease.

BACKGROUND: Accurate measurements of mucosal eosinophil concentrations in gastrointestinal tracts of healthy children are necessary to differentiate health and disease states in general, and better define eosinophilic gastrointestinal diseases. STUDY: We retrospectively reviewed gastrointestinal biopsies from children with macroscopically normal endoscopies, who, after a minimal follow-up of one year, were not diagnosed with any organic disease. Peak eosinophil concentrations and distributions were assessed from each segment of the gastrointestinal tract. RESULTS: Three centers (Italy, United Kingdom, and Israel) contributed 202 patients (median age 13 years IQR 9.5-15.5, range 1-18 years). Median (IQR, range) eosinophil concentrations (eos/mm2) were: esophagus 0 (0-0, 0-84), stomach 0 (0-4, 0-84), duodenal bulb 20 (13-30, 7-67), second part of duodenum 20 (13-29, 0-105), terminal ileum 29 (14-51, 0-247), cecum 53 (37-89, 10-232), ascending colon 55 (25-84, 0-236), transverse colon 38 (21-67, 4-181), descending colon 29 (17-59, 0-114), sigmoid colon 25 (13-40, 0-215) and rectum 13 (4-28, 0-152). Significant geographical variance was present, however, no differences in eosinophil concentrations were identified between children with resolving symptoms vs. those with functional diagnoses, nor across age groups. CONCLUSIONS: Standardized eosinophil concentrations from the gastrointestinal tracts of children without organic disease will serve to better define both health and disease states. No differences were found between resolved symptoms vs. functional diagnoses nor between age groups in this pediatric cohort.

Young-onset gastric cancer and Epstein-Barr Virus (EBV) - a major player in the pathogenesis?

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (≤45 years) compared with an average-onset cohort (≥55 years) and characterize the clinicopathologic pattern of young-onset GC. METHODS: Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records. RESULTS: Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p = 0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p = 0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68 years). MSI-H was found only in the average-onset cohort [0% vs 27%, p = 0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p = 0.002). CONCLUSION: Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.

Tumor Lymphocyte Infiltration Is Correlated with a Favorable Tumor Regression Grade after Neoadjuvant Treatment for Esophageal Adenocarcinoma.

(1) Background: We aimed to explore the association between neoadjuvant treatment, tumor-infiltrating immune lymphocyte (TIL), and tumor-associated macrophage (TAM) and survival in patients with esophageal adenocarcinoma. (2) Methods: Patients who underwent esophagectomy were divided into three groups according to their treatment modality and tumor regression grade (TRG): (i) surgery-only group (SG), (ii) good responders (GR) group (TRG 0−1), and (iii) bad responders (BR) group (TRG 2−3). We then carried out statistical correlations of the immunofluorescence analysis of the immune infiltrate in the esophageal surgical specimens with several clinical and pathological parameters. In addition, we analyzed The Cancer Genomic Atlas (TCGA) dataset for differences in TILs, TAMs, and protein expression in immune pathways. (3) Results: Forty-three patients (SG­15, GR­13, and BR­13) were evaluated. The highest enrichment of CD3+ (p < 0.001), CD8+ (p = 0.001) and CD4+ (p = 0.009) was observed in the stroma of GR patients. On multivariate analysis, only CD8+ T cell and signet-ring features were independent prognostic factors for overall survival. In TCGA analysis, we identified overexpression of TAM and colony-stimulating factor 1 receptor (CSF-1R). (4) Conclusions: High enrichment of lymphocyte subpopulations in the microenvironment of esophageal adenocarcinoma is associated with a favorable response to neoadjuvant treatment and an improved patient outcome.

Tissue and peripheral eosinophilia as predictors for disease outcome in children with ulcerative colitis.

BACKGROUND: Eosinophils are implicated in the pathogenesis of ulcerative colitis. AIMS: To evaluate the magnitude of mucosal and blood eosinophils in newly diagnosed pediatric ulcerative colitis patients and its significance in predicting disease outcomes. METHODS: We retrospectively evaluated colorectal biopsies of 96 pediatric patients with ulcerative colitis and 50 age- and sex-matched controls. Samples were taken from diseased areas of the colon and examined by a gastrointestinal pathologist. The most inflamed site was used for assessment of mucosal eosinophils. RESULTS: Samples from 96 diagnostic and 70 follow-up colonoscopies were evaluated. Median age was 13.3 years (IQR 10.1-15.3). Median duration of follow-up was 12.8 years (IQR 7.2-17.1). Median number of tissue eosinophils at diagnosis was 45 (IQR 22-73) compared to 10 eosinophils (IQR 8-25) during histologic remission (p<0.0001). Peripheral absolute eosinophil counts correlated with tissue inflammation and eosinophilia (p=0.001). Mucosal eosinophilic infiltration (p=0.02) and peripheral eosinophilia (p=0.04) was associated with clinical severity at diagnosis. Multivariate analysis showed that severe eosinophilic infiltration is associated with corticosteroid therapy following diagnosis (p=0.04) but not with long-term risk for step-up therapy or colectomy. CONCLUSION: Tissue and peripheral eosinophilia correlate with ulcerative colitis severity at diagnosis and with short-term corticosteroid requirement but not with long-term outcomes.