Esophageal remodeling in eosinophilic esophagitis.

PURPOSE OF REVIEW: Eosinophilic esophagitis (EoE) is a Th2 immune/antigen-mediated disorder characterized by esophageal dysfunction and eosinophilic inflammation. Worsening dysphagia and food impactions are significant complications associated with esophageal remodeling and fibrostenotic disease. This review highlights the most recent research findings pertaining to mechanisms of sub-epithelial fibrosis in EoE, current diagnostic tools, and therapeutic approaches. RECENT FINDINGS: Recent studies leveraging publicly available single cell sequencing databases and comparative proteomics have furthered our understanding of the mechanisms mediating fibrosis. Fibroblast crosstalk with the extracellular matrix and with epithelial, endothelial, and T cells have been implicated, with the likely existence of multiple fibroblast sub-types. Accurate diagnosis of remodeling with biopsies remains a challenge due to inadequate depth of sampling. Web-based tools incorporating epithelial findings show promise in predicting subepithelial fibrosis. Impedance planimetry with esophageal distensibility measurements are increasingly utilized tools to assess fibrostenotic severity. Immunostaining and luminal captured proteins associated with remodeling show promise as potential molecular markers of fibrosis. Anti-inflammatory therapy may improve esophageal fibrosis and distensibility, although specific fibrosis-targeted therapy is lacking. SUMMARY: Recent studies highlight novel mechanisms of fibrosis in EoE. Improved understanding of these mechanisms may lead to novel diagnostic strategies and therapies, and thereby inform treatment decisions.

Differential Contributions of Fibroblast Subpopulations to Intercellular Communication in Eosinophilic Esophagitis.

Fibroblast heterogeneity remains undefined in eosinophilic esophagitis (EoE), an allergic inflammatory disorder complicated by fibrosis. We utilized publicly available single-cell RNA sequencing data (GSE201153) of EoE esophageal biopsies to identify fibroblast sub-populations, related transcriptomes, disease status-specific pathways and cell-cell interactions. IL13-treated fibroblast cultures were used to model active disease. At least 2 fibroblast populations were identified, F_A and F_B. Several genes including ACTA2 were more enriched in F_A. F_B percentage was greater than F_A and epithelial-mesenchymal transition upregulated in F_B vs. F_A in active and remission EoE. Epithelial-mesenchymal transition was also upregulated in F_B in active vs. remission EoE and TNF-α signaling via NFKB was downregulated in F_A. IL-13 treatment upregulated ECM-related genes more profoundly in ACTA2- fibroblasts than ACTA2+ myofibroblasts. After proliferating epithelial cells, F_B and F_A contributed most to cell-cell communication networks. ECM-Receptor interaction strength was stronger than secreted or cell-cell contact signaling in active vs. remission EoE and significant ligand-receptor pairs were driven mostly by F_B. This unbiased analysis identifies at least 2 fibroblast sub-populations in EoE in vivo, distinguished in part by ACTA2. Fibroblasts play a critical role in cell-cell interactions in EoE, most profoundly via ECM-receptor signaling via the F_B sub-group.

The Travels of Signet-Ring Cell Carcinoma: From Colon to Stomach and Duodenum.

Colorectal cancer (CRC) metastasizing to the stomach and duodenum is rare. Even rarer is when the CRC subtype is signet-ring cell carcinoma (SRCC). Endoscopic findings of CRC metastasis to the stomach have been described as solitary and submucosal while duodenal metastasis has been observed to be exophytic. In this report, we describe a case of a middle-aged man with colon SRCC presenting with oral intolerance. He was found to have concurrent metastases to the stomach and duodenum and died 8 months after his SRCC diagnosis.