Pathologie (Heidelberg, Germany)最新文献

Background: Conventional histopathology faces methodological limitations when assessing complex three-dimensional tissue architectures. In particular, for heterogeneous tissues such as the pancreas or in complex tissue pathologies, restriction to two-dimensional sections hampers comprehensive recognition of morphological features.

Objective: This study aims to demonstrate the potential of synchrotron-based phase-contrast imaging (SRµCT) as a tool for high-resolution visualization of pancreatic tissue. Three representative case examples were analyzed to capture morphological parameters volumetrically and correlate them with immunohistochemical marker profiles.

Materials and methods: Tissue cores from formalin-fixed, paraffin-embedded human pancreatic samples were volumetrically assessed using SRµCT. The investigated material was further processed as microarrays. Serial sections and immunohistochemical stains were correlated with the 3D datasets.

Results: SRµCT enabled detailed spatial visualization of functional compartments and neoplastic infiltration patterns. Non-neoplastic tissue revealed distinct morphological compartments. A well-differentiated neuroendocrine tumor exhibited trabecular architecture, whereas ductal adenocarcinoma displayed infiltrative growth with diffuse, heterogeneous architecture, irregular duct formations and stromal desmoplasia. Virtual slicing permitted orientation-independent analyses. Correlation with immunohistochemical profiles validated the morphofunctional findings.

Conclusion: SRµCT is a sensitive, non-invasive technique providing label-free 3D insights into pancreatic architecture. It opens new perspectives for research, teaching, and potentially advanced diagnostic applications.

Enfortumab vedotin (EV) is a targeted antibody-drug conjugate (ADC) directed against NECTIN4 and approved for treatment of metastatic urothelial carcinoma (mUC) after failure of platinum-based chemotherapy and immune checkpoint inhibitors. However, not all patients benefit equally from EV, highlighting the need for a predictive biomarker. In this multicenter study, 108 EV-treated mUC patients were analyzed for genomic NECTIN4 amplifications using fluorescence in situ hybridization (FISH). Approximately one-quarter of tumors showed NECTIN4 amplification, which was strongly associated with increased membranous protein expression and an objective response rate of 96%. Amplified tumors also had significantly prolonged overall survival. In a control cohort without EV, NECTIN4 amplification had no prognostic impact. These findings identify NECTIN4 amplification as a stable, predictive biomarker that may guide treatment decisions in mUC. Data from TCGA further suggest a cross-entity relevance of NECTIN4 amplification, supporting future clinical exploration of EV in other solid tumors.

For years, a growing number of museums and scientific institutions have been taking responsibility for their past by initiating provenance research in their collections and addressing the contexts of injustice uncovered in the process. This article presents a project at the Institute of Anatomy in Leipzig, which is examining the provenance of more than 600 human skulls and heads from colonial contexts. These ancestral remains are part of a historical skull collection at the university, which is to be dissolved in the long term. The authors provide insights into their approach to involving today's countries and communities of origin and report on initial research findings. These relate to the history of the collection, the deceased individuals, the collectors and their networks, and the circumstances surrounding the acquisition of ancestral remains. Finally, repatriation as a goal of provenance research and the challenges associated with it are discussed.

Background: Hungary ranks highest in the world regarding both the incidence and death rates of colorectal cancer. Novel analytical methods have surfaced in the past decade and are infiltrating the field of medicine. Infrared spectroscopy (IR) and mass spectrometry (MS) are frequently used for such measurements; however, multimodal techniques resulting from the combination of these have not yet gained widespread adoption.

Methods: Tissue microarray (TMA) of colorectal adenocarcinomas, liver metastases, and surrounding colon tissues were prepared at the Institute of Pathology, Forensic, and Insurance Medicine, Semmelweis University. From the block, 2‑ and 10-µm sections were cut for infrared and MS imaging, respectively. Infrared measurements were performed with a Perkin Elmer Spotlight microscope (Perkin Elmer Inc., Waltham, MA, USA) on samples with an area of 2200 × 2200 µm², in the wavenumber range of 4000-750 cm^-1. For the mass spectrometry measurements, a custom Waters Xevo G2 XS QToF-type lipid group focusing device (Waters Corporation, Santa Barbara, CA, USA) was used on samples with an area of 10 mm × 10 mm between 150-900 m/z values. The uniqueness of the device comes from the fact that a high-energy laser had been added for the purpose of ionizing the sample tissue.

Results: The spectral results from the samples were noise filtered in both methods to separate the sample signal from the background. Overall, 41 cores were suitable for further data processing. For the measurements with infrared spectroscopy, the three-class classification resulted in accuracy of 0.71 and 0.71 using C‑support vector classification (SVC) and eXtreme Gradient Boosting (XGBoost) algorithms. For the analysis of the mass spectrometry data, 0.65 and 0.70 accuracy values were observed.

Conclusion: Identical TMA slides have been imaged with two analytical methods. The performance of the separating algorithms was very close, which underscores the efficacy of the spectroscopy and spectrometry approach. A vector database of the spectra could be combined with the whole-slide image pixels obtained by a traditional digital scanner. A further step could be a thickness-optimized measurement, which would determine the setting for the combined measurement of the exact same sample.

Background and objective: Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic manifestations, particularly renal disease. While the underlying pathomechanisms are still largely unknown, these manifestations are thought to develop either directly, i.e., by HEV infection of the respective organ, or indirectly, i.e., via immunologic reactions. Herein, we describe the development of de novo immune complex-mediated glomerulonephritis (GN) associated with the glomerular deposition of a newly described form of the HEV open reading frame 2 (ORF2) capsid protein in patients with chronic or acute hepatitis E.

Methods: We performed immunostaining, electron and deconvolution microscopy, and laser-capture microdissection combined with mass spectrometry to specifically investigate the glomerular compartment.

Results: In a kidney transplant recipient with chronic hepatitis E, we show that GN developed in parallel with increasing glomerular deposits of the HEV ORF2 protein, which significantly colocalizes with IgG, thus forming immune complexes. Interestingly, the glomerular HEV ORF2 protein does not correspond to the expected secreted and glycosylated form of the viral capsid protein but rather has the molecular weight of a truncated non-glycosylated form. Importantly, it is not associated with HEV RNA and, in contrast to the situation in liver cells, no productive HEV infection of kidney cells is detected. Patients with acute hepatitis E show similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN.

Conclusion: The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN, establish hepatitis E-associated GN as a distinct entity, and suggest therapeutic implications.

Young professionals may find it appealing to pursue specialist training in Austria due to the country's geographical proximity and the mutual recognition of medical specialists.When considering a career change, it is important to be aware of the differences in the structure and requirements of specialty training programs and in scientific career opportunities.Specialist training in Austria requires the completion of a mandatory nine-month basic training program. It is more structured, with a strict division between basic training and specialized training in the subsequent specialist training program. The specialization training also offers greater flexibility for trainees, allowing them to customize their learning experience and advance their skills in a way that suits their individual needs and goals.In addition, before making a final decision, one must take into account the disparities in scientific development prospects.