Identification of pathologic features associated with “ulcerative colitis-like” Crohn’s disease

AIM: To identify pathologic features associated with this “ulcerative colitis (UC)-like” subgroup of Crohn’s disease (CD). METHODS: Seventeen subjects diagnosed as having UC who underwent proctocolectomy (RPC) from 2003-2007 and subsequently developed CD of the ileal pouch were identified. UC was diagnosed based on pre-operative clinical, endoscopic, and pathologic studies. Eighteen patients who underwent RPC for UC within the same time period without subsequently developing CD were randomly selected and used as controls. Pathology reports and histological slides were reviewed for a wide range of gross and microscopic pathological features, as well as extent of disease. The demographics, gross description and histopathology of the resection specimens were reviewed and compared between the two groups. RESULTS: Patients with “UC-like” CD were on average 13 years younger than those with “true” UC (P < 0.01). More severe disease in the proximal involved region and active ileitis with/without architectural distortion were observed in 6 of 17 (35%) and 7 of 17 (41%) “UC-like” CD cases, respectively, but in none of the “true” UC cases (P < 0.05). Active appendicitis occurred in 8 of 16 (50%) “UC-like” CD cases but in only two (11%) “true” UC cases (P < 0.05). Conspicuous lamina propria neutrophils were more specific for “UC-like” CD (76% vs 22%, P < 0.05). In addition, prominent lymphoid aggregates tended to be more common in “UC-like” CD (P = 0.07). The “true” UC group contained a greater number of cases with severe activity (78% vs 47%). Therefore, the features more commonly seen in “UC-like” CD were not due to a more severe disease process. Crohn’s granulomas and transmural inflammation in non-ulcerated areas were absent in both groups. CONCLUSION: More severe disease in the proximal involved region, terminal ileum involvement, active appendicitis, and prominent lamina propria neutrophils may be morphological factors associated with “UC-like” CD

Heterogeneity of glycan biomarker clusters as an indicator of recurrence in pancreatic cancer

IntroductionOutcomes following tumor resection vary dramatically among patients with pancreatic ductal adenocarcinoma (PDAC). A challenge in defining predictive biomarkers is to discern within the complex tumor tissue the specific subpopulations and relationships that drive recurrence. Multiplexed immunofluorescence is valuable for such studies when supplied with markers of relevant subpopulations and analysis methods to sort out the intra-tumor relationships that are informative of tumor behavior. We hypothesized that the glycan biomarkers CA19-9 and STRA, which detect separate subpopulations of cancer cells, define intra-tumoral features associated with recurrence.MethodsWe probed this question using automated signal thresholding and spatial cluster analysis applied to the immunofluorescence images of the STRA and CA19-9 glycan biomarkers in whole-block sections of PDAC tumors collected from curative resections.ResultsThe tumors (N = 22) displayed extreme diversity between them in the amounts of the glycans and in the levels of spatial clustering, but neither the amounts nor the clusters of the individual and combined glycans associated with recurrence. The combined glycans, however, marked divergent types of spatial clusters, alternatively only STRA, only CA19-9, or both. The co-occurrence of more than one cluster type within a tumor associated significantly with disease recurrence, in contrast to the independent occurrence of each type of cluster. In addition, intra-tumoral regions with heterogeneity in biomarker clusters spatially aligned with pathology-confirmed cancer cells, whereas regions with homogeneous biomarker clusters aligned with various non-cancer cells.ConclusionThus, the STRA and CA19-9 glycans are markers of distinct and co-occurring subpopulations of cancer cells that in combination are associated with recurrence. Furthermore, automated signal thresholding and spatial clustering provides a tool for quantifying intra-tumoral subpopulations that are informative of outcome

Comprehensive Genomic Profiling of Pancreatic Acinar Cell Carcinomas

significantly enriched for genomic alterations (GAs) causing inactivation of DNA repair genes (45%); these GAs have been associated with sensitivity to platinum-based therapies and PARP inhibitors. Collectively, these results identify potentially actionable GAs in the majority of PACCs, and provide a rationale for using personalized therapies in this disease. Statement of Significance PACC is genomically distinct from other pancreatic cancers. Fusions in RAF genes and mutually exclusive inactivation of DNA repair genes represent novel potential therapeutic targets that are altered in over two-thirds of these tumors

Mechanisms of Resistance in Gastroenteropancreatic Neuroendocrine Tumors

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs), although curable when localized, frequently metastasize and require management with systemic therapies, including somatostatin analogues, peptide receptor radiotherapy, small-molecule targeted therapies, and chemotherapy. Although effective for disease control, these therapies eventually fail as a result of primary or secondary resistance. For small-molecule targeted therapies, the feedback activation of the targeted signaling pathways and activation of alternative pathways are prominent mechanisms, whereas the acquisition of additional genetic alterations only rarely occurs. For somatostatin receptor (SSTR)-targeted therapy, the heterogeneity of tumor SSTR expression and dedifferentiation with a downregulated expression of SSTR likely predominate. Hypoxia in the tumor microenvironment and stromal constituents contribute to resistance to all modalities. Current studies on mechanisms underlying therapeutic resistance and options for management in human GEP-NETs are scant; however, preclinical and early-phase human studies have suggested that combination therapy targeting multiple pathways or novel tyrosine kinase inhibitors with broader kinase inhibition may be promising

Analysis of factors influencing the organizational capacity of Institutional Review Boards In China: a crisp-set Qualitative Comparative Analysis based on 107 cases

Abstract Background Institutional Review Boards (IRBs) play a vital role in safeguarding the rights and interests of both research participants and researchers. However, China initiated the establishment of its own IRB system relatively late in comparison to international standards. Despite commendable progress, there is a pressing need to strengthen the organizational capacity building of Chinese IRBs. Hence, this study aims to analyze the key factors driving the enhancement of organizational capacity within these committees. Method The cross-sectional survey for this research was conducted from July 2020 to January 2022. Following the statistical grouping based on the "2020 China Health Statistical Yearbook", a systematic investigation of IRBs in various provinces of China was carried out. In-depth interviews and questionnaire surveys were conducted with the chairpersons and administrative executives (or secretaries) of highly cooperative IRBs. Subsequently, data were collected from 107 IRBs. Qualitative Comparative Analysis (QCA) was employed as the method to analyze the factors influencing the organizational capacity of medical ethics committees and explore the diverse combinations of these factors. Results Through a singular necessary condition analysis, the variable "protection of rights and interests" emerges as a critical factor contributing to the robust construction of Institutional Review Boards Institutional Review Boards (IRBs). Conversely, the variables of "lack of member ability, absence of review process, and deficiency in the supervision mechanism" collectively constitute a sufficient condition leading to weaker IRB construction. The state analysis uncovers three interpretation modes: member ability-oriented (M1), system process-oriented mode (M2), and resource system-oriented mode (M3). Conclusions The results of this study are effectively explicable using the "Triangular Force" model proposed for the hypothesis of IRBs' organizational capacity, which provides a solid foundation for the development of organizational capabilities in IRBs. To enhance the organizational capacity of IRBs in China, it is imperative to elevate the competence of committee members and strengthen team development. This can be achieved by establishing a comprehensive regulatory framework and refining procedural protocols. Moreover, clarifying the organizational structure and optimizing resource allocation are essential steps in bolstering the overall organizational capabilities of these committees