Background: Intestinal barrier dysfunction is a hallmark of inflammatory bowel disease (IBD), yet the clinical significance of tight junction (TJ) remodeling remains unclear. We investigated whether alterations in the expression and localization of key TJ proteins are associated with disease activity and clinical outcomes in IBD. Methods: This retrospective, single-center study included patients with Crohn’s disease (CD; n = 100), ulcerative colitis (UC; n = 120), and healthy controls (n = 80). Immunohistochemistry was used to assess the expression and subcellular localization of occludin and claudin-1 separately in surface (SE) and crypt epithelium (CR), with staining classified as predominantly membranous (regular) or cytoplasmic (irregular). The primary endpoint was IBD-related hospitalization. Secondary endpoints included surgery, initiation of biologic therapy, and clinical relapse. Logistic and Cox regression models were applied, and longitudinal changes were assessed in paired biopsies. Results: Both occludin and claudin-1 were dysregulated in active disease, showing increased expression and cytoplasmic redistribution compared with remission and controls. TJ alterations were more pronounced in the CR and correlated with clinical, endoscopic, and histological activity. In CD, occludin CR overexpression was independently associated with hospitalization (aOR 1.010; p = 0.05) and surgery (aHR 1.013; p = 0.005), while irregular occludin CR staining was associated with initiation of biologic therapy (aOR 3.48; p = 0.03). In UC, increased occludin CR levels and irregular CR staining were associated with IBD-related hospitalization in multivariable analyses (aOR 1.014; p = 0.035 and aOR 2.78; p = 0.032, respectively). Higher occludin CR levels identified UC patients at increased risk of clinical relapse (aHR 1.012; p = 0.002). In paired biopsies (n = 127), TJ architecture—particularly in the CR—improved over time, with reduced expression and a shift toward membranous localization, most prominently in bio-experienced patients. Conclusions: TJ remodeling, particularly crypt-level occludin dysregulation, is associated with disease activity and clinical outcomes, capturing a clinically relevant dimension of epithelial barrier dysfunction in IBD.

Background/Objectives: Adenocarcinomas of the esophagogastric and gastric areas are often managed with a multimodal treatment including neoadjuvant chemotherapy and surgery. The impact of neoadjuvant chemotherapy on the host’s antitumoral immune response remains largely unknown. Methods: A retrospective review of a single-institution cohort of patients with adenocarcinoma of the stomach or esophagogastric area undergoing curative intent surgery after neoadjuvant chemotherapy FLOT (Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel) was reviewed. After institutional ethics approval, pathologic slides were re-reviewed and tumor-infiltrating lymphocyte scores were calculated. Tumor-infiltrating lymphocytes (TILs) were studied in conjunction with tumor regression scores (TRG) and the degree of regression in the involved lymph nodes as well as in correlation with the lymph node ratio (the ratio of involved lymph nodes over the total number of lymph nodes resected). Results: A total of 106 patients were reviewed. No statistical correlation could be established between the tumor-infiltrating lymphocyte scores and the degree of regression in the primary tumor as well as with the partial response to chemotherapy of pathologically involved lymph nodes. The TIL score also did not correlate with the lymph node ratio in our patient cohort. A strong correlation was noted between TILs and lymph nodes that completely regressed after neoadjuvant chemotherapy. Conclusions: Tumor-infiltrating lymphocytes do not correlate with the response of the primary tumor or the partial response of the involved lymph nodes, but only with the complete response to neoadjuvant chemotherapy of tumor-involved lymph nodes. Our study focuses on the effects of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes compared to the effects on the primary tumor and the involved lymph nodes.