Hasil untuk "Pathology"

T. Kajitani, The International Consortium for Outcome Research in H Cancer

C. S. Hallpike, H. Cairns

M. Osborn, K. Weber

H. Schuknecht, M. Gacek

D. Schoepp, P. Conn

M. Casanova, D. Buxhoeveden, A. Switala et al.

M. Baggiolini

Lavinia Ghiani, Simona Citro, Alessandro Medda et al.

Abstract Background Head and Neck Squamous Cell Carcinoma (HNSCC) are classified in two main subtypes: HPV-positive (HPV+), driven by human papillomavirus (HPV) infections, and HPV-negative (HPV-), associated with environmental risk factors. Despite molecular and clinicopathological differences, neither subtype has effective tailored therapies. Since high-risk HPV oncoproteins E6/E7 affect several epigenetic regulators, characterizing the epigenetic landscape of HPV+ and HPV- HNSCC may uncover novel subtype-specific biomarkers and therapeutic targets. Methods Histone post-translational modifications were profiled in HPV+ and HPV- HNSCC tissues and cell lines using super-SILAC mass spectrometry. The same analysis was performed and combined with RNA-sequencing on E6/E7-transduced human primary keratinocytes (HKs) to identify relevant histone modifiers affected by HPV oncoproteins. Candidate gene was validated via E6/E7-mediated-siRNA knockdown in HPV + cell lines. Western Blot, RT-qPCR and Immunohistochemistry assessed gene expression. NSD2 expression was examined in patients’ tissue samples, TCGA data and 14 HNSCC cell lines. shRNA-mediated NSD2 knockdown followed by RNA-seq, cell proliferation and migration assays evaluated its oncogenic role in HNSCC. CaCl2 treatments were used to investigate NSD2’s role in epithelial differentiation, while ALDH-positive cells were quantified by flow-cytometry. NSD2 overexpression was used to confirm results. Results HPV+ HNSCC exhibited elevated H3K36me2 levels, compared to HPV-. This alteration is driven by E6/E7-induced NSD2 upregulation. NSD2, a histone methyltransferase specific for H3K36 di-methylation is overexpressed in HPV+ relative to HPV- HNSCC and in both subtypes compared to normal tissue, suggesting crucial implications in HNSCC. Functional assays revealed that NSD2 promotes cell proliferation and migration in both the subtypes. Notably, we identified a novel role for NSD2 in inhibiting epithelial cell differentiation, particularly in HPV+ HNSCC, where its upregulation mediates the E6/E7-induced differentiation blockade. Conclusions We identified a novel HPV-driven epigenetic signature in HNSCC marked by increased H3K36me2 and its writer, NSD2. Our study highlights H3K36me2 as a potential biomarker for patient stratification and positions NSD2 as a promising therapeutic target across HNSCC subtypes, modulating both common and subtype-specific oncogenic pathways. Specifically, NSD2 inhibition in HPV+ tumors restores epithelial differentiation, offering a potential strategy to arrest tumor progression.

G. Rajkowska, J. Miguel-Hidalgo

M. Norenberg, Jon Smith, A. Marcillo

M. Vercellino, F. Plano, B. Votta et al.

M. Stanley

Abhinav Kumar Singh, Oshan Shrestha, Reetu Baral et al.

Visceral leishmaniasis (VL) is widespread in tropical and temperate region. It is caused by the protozoan parasite leishmania species and is transmitted through the bite of infected female sandflies. It manifests as pancytopenia, hepatosplenomegaly and fever. Here, we present a case of 20-year-old male presented with difficulty in swallowing for 2 months, abdominal distention for 30 days and shortness of breath for 20 days along with progressive renal impairment. Clinical examination revealed hepatosplenomegaly and laboratory investigations confirmed pancytopenia, nephrotic range proteinuria, hematuria and hypocomplementemia. Bone marrow aspiration and biopsy was performed which showed leishmania donovani (LD) bodies. It’suncommon presentation makes it challenging for physicians as well as pathologist to make a timely diagnosis.

Justus Kaufmann, Maximilian Haist, Ivan-Maximiliano Kur et al.

The growth pattern of oropharyngeal squamous cell carcinomas (OPSCC) varies from compact tumor cell aggregates to diffusely infiltrating tumor cell-clusters. The influence of the growth pattern on local tumor control and survival has been studied mainly for surgically treated oral cavity carcinomas on a visual basis. In this study, we used multiplex immunofluorescence staining (mIF) to examine the antigens pan-cytokeratin, p16INK4a, Ki67, CD271, PD-L1, and CD8 in pretherapeutic biopsies from 86 OPSCC. We introduce Tumor-stroma contact ratio (TSC), a novel parameter, to quantify the relationship between tumor cells in contact with the stromal surface and the total number of epithelial tumor cells. mIF tumor cores were analyzed at the single-cell level, and tumor-stromal contact area was quantified using the R package ''Spatstat''. TSC was correlated with the visually assessed invasion pattern by two independent investigators. Furthermore, TSC was analyzed in relation to clinical parameters and patient survival data to evaluate its potential prognostic significance.Higher TSC correlated with poor response to (chemo-)radiotherapy (r = 0.3, p < 0.01), and shorter overall (OS) and progression-free (PFS) survival (median OS: 13 vs 136 months, p < 0.0001; median PFS: 5 vs 85 months, p < 0.0001). Visual categorization of growth pattern according to established criteria of tumor aggressiveness showed interobserver variability increasing with more nuanced categories (2 categories: k = 0.7, 95 %-CI: 0.55 - 0.85; 4 categories k = 0.48, 95 %-CI: 0.35 - 0.61).In conclusion, TSC is an objective and reproducible computer-based parameter to quantify tumor-stroma contact area. We demonstrate its relevance for the response of oropharyngeal carcinomas to primary (chemo-)radiotherapy.

Nguyen Xuong Duong, Minh Sam Thai, Ngoc Sinh Tran et al.

Kidney transplantation (KT) is a preferred treatment for end-stage renal disease (ESRD) because it offers better long-term survival and cost-effectiveness compared to dialysis. Significant global disparities persist in access to KT, particularly in low- and middle-income countries (LMICs). This study aims to assess the epidemiology and outcomes of KT in LMICs while examining the relationship between a country’s income level and its KT prevalence. A systematic review of the literature was conducted, with searches of PubMed, Scopus, and Web of Science from inception to 31 May 2024. Relevant articles reporting on the epidemiology and outcomes of KT or ESRD patients undergoing kidney replacement therapy (KRT) in LMICs were included. A total of 8054 articles were identified, with 972 articles selected for full-text screening after initial title and abstract review. Following full-text screening, 35 articles met the inclusion criteria. The data showed significant variation in KRT and KT prevalence across different geographical locations. Higher-income countries within LMICs tended to have higher KT prevalence rates. Barriers such as inadequate healthcare infrastructure, limited financial resources, and insufficient organ donation frameworks were identified as contributing factors to the low KT rates in these regions. The study highlights the disparities in KT access and prevalence in LMICs, underscoring the need for targeted interventions and international collaboration to address these gaps. Efforts to increase both living and deceased donor transplants, expand health system capacity, and incorporate KT in healthcare planning are needed to close this gap. Global partnerships spearheaded by organizations such as The Transplantation Society (TTS) and the International Society of Nephrology (ISN) are crucial for improving KT rates and outcomes in LMICs.

Xue Yang, Zexuan Liu, Weiwei Tang et al.

Endometrial carcinoma (ECa) is the fourth most common cancer among women. The oncogene PELP1 is frequently overexpressed in a variety of cancers, including ECa. We recently generated SMIP34, a small‐molecule inhibitor of PELP1 that suppresses PELP1 oncogenic signaling. In this study, we assessed the effectiveness of SMIP34 in treating ECa. Treatment of established and primary patient‐derived ECa cells with SMIP34 resulted in a significant reduction of cell viability, colony formation ability, and induction of apoptosis. RNA‐seq analyses showed that SMIP34‐regulated genes were negatively correlated with ribosome biogenesis and eukaryotic translation pathways. Mechanistic studies showed that the Rix complex, which is essential for ribosomal biogenesis, is disrupted upon SMIP34 binding to PELP1. Biochemical assays confirmed that SMIP34 reduced ribosomal biogenesis and new protein synthesis. Further, SMIP34 enhanced the efficacy of mTOR inhibitors in reducing viability of ECa cells. SMIP34 is also effective in reducing cell viability in ECa organoids in vitro and explants ex vivo. Importantly, SMIP34 treatment resulted in a significant reduction of the growth of ECa xenografts. Collectively, these findings underscore the potential of SMIP34 in treating ECa.

A. Bombonati, D. Sgroi

L. Pantanowitz, P. Valenstein, A. Evans et al.

Whole slide imaging (WSI), or "virtual" microscopy, involves the scanning (digitization) of glass slides to produce "digital slides". WSI has been advocated for diagnostic, educational and research purposes. When used for remote frozen section diagnosis, WSI requires a thorough implementation period coupled with trained support personnel. Adoption of WSI for rendering pathologic diagnoses on a routine basis has been shown to be successful in only a few "niche" applications. Wider adoption will most likely require full integration with the laboratory information system, continuous automated scanning, high-bandwidth connectivity, massive storage capacity, and more intuitive user interfaces. Nevertheless, WSI has been reported to enhance specific pathology practices, such as scanning slides received in consultation or of legal cases, of slides to be used for patient care conferences, for quality assurance purposes, to retain records of slides to be sent out or destroyed by ancillary testing, and for performing digital image analysis. In addition to technical issues, regulatory and validation requirements related to WSI have yet to be adequately addressed. Although limited validation studies have been published using WSI there are currently no standard guidelines for validating WSI for diagnostic use in the clinical laboratory. This review addresses the current status of WSI in pathology related to regulation and validation, the provision of remote and routine pathologic diagnoses, educational uses, implementation issues, and the cost-benefit analysis of adopting WSI in routine clinical practice.

Xiaohang Yang, Jingjing Yin, Yu Fu et al.

Abstract Introduction Myometrial invasion is a prognostic factor for lymph node metastases and decreased survival in non-endometrioid endometrial carcinoma patients. Herein, we explored the mode of myometrial invasion diagnosis in FIGO stage I non-endometrioid carcinoma and evaluated the differences in diagnostic efficiency among intraoperative frozen section (IFS), intraoperative gross examination (IGE), magnetic resonance imaging (MRI), and computed tomography (CT) in clinical practice. Finally, we suggested which test should be routinely performed. Method This was a historical cohort study nationwide with 30 centers in China between January 2000 and December 2019. Clinical data, including age, histology, method of myometrial invasion evaluation (MRI, CT, IGE, and IFS), and final diagnosis of postoperative paraffin sections, were collected from 490 non-endometrioid endometrial carcinoma (serous, clear cell, undifferentiated, mixed carcinoma, and carcinosarcoma) women in FIGO stage I. Results Among the 490 patients, 89.59% presented myometrial invasion. The methods reported for myometrial invasion assessment were IFS in 23.47%, IGE in 69.59%, MRI in 37.96%, and CT in 10.20% of cases. The highest concordance was detected between IFS and postoperative paraffin sections (Kappa = 0.631, accuracy = 93.04%), followed by IGE (Kappa = 0.303, accuracy = 82.40%), MRI (Kappa = 0.131, accuracy = 69.35%), and CT (Kappa = 0.118, accuracy = 50.00%). A stable diagnostic agreement between IFS and the final results was also found through the years (2000–2012: Kappa = 0.776; 2013–2014: Kappa = 0.625; 2015–2016: Kappa = 0.545; 2017–2019: Kappa = 0.652). Conclusion In China, the assessment of myometrial invasion in non-endometrioid endometrial carcinoma is often performed via IGE, but the reliability is relatively low in contrast to IFS. In clinical practice, IFS is a reliable method that can help accurately assess myometrial invasion and intraoperative decision-making (lymph node dissection or not). Hence, it should be routinely performed in non-endometrioid endometrial carcinoma patients.

Petter Gottschalk

Half of all finance and insurance firms in Norway report that they are exposed to economic crime, particularly fraud, every year. On the other hand, only eighteen percent in public administration and defense perceive similar exposure to economic crime. However, the estimated fraction of unreported, non-registered economic crime in the country is ninety-four percent. These numbers are some of the results from surveys conducted in Norway in 2005, 2010, and 2023. This article applies the main economic crime categories of fraud, theft, manipulation, and corruption as used by scholars to study the survey results. The corruption category shows the largest gap between perceived exposure and police statistics. Comparison to white-collar crime research indicates higher frequency of theft at the street level and higher frequency of manipulation at the upper echelon. Comparison to future surveys in other countries is encouraged.