Pathologie (Heidelberg, Germany)最新文献

{"title":"Reconstructing 3D histological structures using machine learning (artificial intelligence) algorithms.","authors":"J Báskay, M Kivovics, D Pénzes, E Kontsek, A Pesti, A Kiss, M Szócska, O Németh, P Pollner","doi":"10.1007/s00292-024-01387-6","DOIUrl":"https://doi.org/10.1007/s00292-024-01387-6","url":null,"abstract":"<p><strong>Background: </strong>Histomorphometry is currently the gold standard for bone microarchitectural examinations. This relies on two-dimensional (2D) sections to deduce the spatial properties of structures. Micromorphometric parameters are calculated from these sections based on the assumption of a plate-like 3D microarchitecture, resulting in the loss of 3D structure due to the destructive nature of classical histological processing.</p><p><strong>Materials and methods: </strong>To overcome the limitation of histomorphometry and reconstruct the 3D architecture of bone core biopsy samples from 2D histological sections, bone core biopsy samples were decalcified and embedded in paraffin. Subsequently, 5 µm thick serial sections were stained with hematoxylin and eosin and scanned using a 3DHISTECH PANNORAMIC 1000 Digital Slide Scanner (3DHISTECH, Budapest, Hungary). A modified U‑Net architecture was trained to categorize tissues on the sections. LoFTR feature matching combined with affine transformations was employed to create the histologic reconstruction. Micromorphometric parameters were calculated using Bruker's CTAn software (v. 1.18.8.0, Bruker, Kontich, Belgium) for both histological and microCT datasets.</p><p><strong>Results: </strong>Our method achieved an overall accuracy of 95.26% (95% confidence interval (CI): [94.15%, 96.37%]) with an F‑score of 0.9320 (95% CI: [0.9211, 0.9429]) averaged across all classes. Correlation coefficients between micromorphometric parameters measured on microCT imaging and histological reconstruction showed a strong linear relationship, with Spearman's ρ‑values of 0.777, 0.717, 0.705, 0.666, and 0.687 for bone volume/tissue volume (BV/TV), bone surface/TV, trabecular pattern factor, trabecular thickness, and trabecular separation, respectively. Bland-Altman and mountain plots indicated good agreement between the methods for BV/TV measurements.</p><p><strong>Conclusion: </strong>This method enables examination of tissue microarchitecture in 3D with an even higher resolution than microcomputed tomography (microCT), without losing information on cellularity. However, the limitation of this procedure is its destructive nature, which precludes subsequent mechanical testing of the sample or any further secondary measurements. Furthermore, the number of histological sections that can be created from a single sample is limited.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key considerations when implementing new diagnostic technologies in routine practice.","authors":"Jochen Lennerz","doi":"10.1007/s00292-024-01396-5","DOIUrl":"https://doi.org/10.1007/s00292-024-01396-5","url":null,"abstract":"<p><strong>Background: </strong>The field of pathology is evolving with the integration of advanced and artificial-intelligence-powered diagnostic technologies. However, there remains a significant gap in clearly outlining the key considerations for the effective implementation of these innovations into clinical care.</p><p><strong>Objectives: </strong>The aim of this review was to identify and address the essential aspects required to bridge the implementation gap of new diagnostic technologies in pathology.</p><p><strong>Material and methods: </strong>This review synthesizes key elements from relevant scientific journals, organizational websites, and practical examples from pathology practice. The findings are presented as a structured framework of six key elements, supported by an infographic and illustrative cases from clinical settings.</p><p><strong>Results: </strong>The key elements are: (1) Innovation depends more on the people driving it than on the work it demands, highlighting the importance of team collaboration and communication; (2) in-depth knowledge of the delivery system emphasizing the importance of care, IT, and administrative layers is crucial; (3) data-driven decision-making in healthcare transformation is central, with an emphasis on the process of converting real-world data (RWD) into actionable real-world evidence (RWE); (4) a proven approach for practice transformation uses a structured (utilization management strategy, UMS) framework; (5) a balanced approach toward financial sustainability, including local and systemic financial strategies, is important; and (6)  ensuring safe and effective progress requires a new, collaborative definition of regulatory science, aligning innovation with regulatory oversight to support technological advancements.</p><p><strong>Conclusion: </strong>These key aspects offer a foundational framework for integrating new technologies into healthcare. Although not exhaustive, overlooking them would miss a significant opportunity to enhance patient care.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Microsatellite instability-What should be considered in routine examinations?]","authors":"Wolfgang Dietmaier, Daniela Hirsch, Josef Rüschoff","doi":"10.1007/s00292-024-01392-9","DOIUrl":"10.1007/s00292-024-01392-9","url":null,"abstract":"","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Centers for experimental animal pathology still occupy a small but valuable niche in translational medicine-time for change?]","authors":"Tanja Poth, Peter Schirmacher","doi":"10.1007/s00292-024-01383-w","DOIUrl":"https://doi.org/10.1007/s00292-024-01383-w","url":null,"abstract":"<p><p>Since CRISPR/Cas systems can be easily used to establish new genetically engineered mouse models, application of these models in the translational research field to explore predictive and therapeutic approaches for human diseases is rising.Integrative centers for experimental animal pathology, such as the CMCP in Heidelberg and the CEP in Munich, link the veterinary and human pathology discipline and contribute substantially to meaningful study results by combining the technical, research, and diagnostic expertise for phenotyping, evaluating, and interpretating complex animal models in the context of human pathology. They provide high-quality tissue processing in a broad spectrum of standard and specialized tissue-based technologies. The histopathology platform enables animal model evaluation including phenotyping, scoring, and detecting species-specific \"background lesions.\" By providing essential prerequisites for high-quality, reproducible, and sustainable research in translational medicine, facilities for experimental animal pathology optimally fulfill the requirements for publications in top-class professional journals, contribute to the implementation of the 3R principle for animal welfare, and help to reduce costs in the preclinical research.The importance of animal models reflecting human diseases will increase in the future but the requirements for high-quality tissue processing and comparative pathology/morphological phenotyping cannot be met by single facilities in a niche position. To cover the existing gap and expected rising demand in the German and European translational research landscape, further facilities for experimental animal pathology that are integrated in the human pathology environment should be established.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and prognostic biomarkers for pancreatic neuroendocrine neoplasms.","authors":"Andreas F-P Sonnen, Anna Vera D Verschuur, Lodewijk A A Brosens","doi":"10.1007/s00292-024-01393-8","DOIUrl":"https://doi.org/10.1007/s00292-024-01393-8","url":null,"abstract":"<p><p>This review examines the diagnostic and prognostic biomarkers for pancreatic neuroendocrine neoplasms (PanNENs), a heterogeneous group of tumors with expression of neuroendocrine markers. PanNENs include both well-differentiated pancreatic neuroendocrine tumors (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). The diagnosis is confirmed through markers such as chromogranin A, synaptophysin, and INSM1, which establish neuroendocrine differentiation. The World Health Organization classification categorizes PanNENs based on tumor differentiation and proliferative activity (Ki-67 and/or mitotic index) into well-differentiated PanNETs (grade 1 to grade 3) and poorly differentiated PanNECs. In most cases, the morphology and proliferation index are sufficient to distinguish PanNETs from PanNECs. However, distinguishing grade 3 PanNETs from PanNECs can be challenging on the basis of morphology and proliferative activity alone. Additional key diagnostic markers for distinguishing grade 3 PanNET from PanNEC include SSTR2A expression and molecular immunohistochemical markers such as p53, Rb1, menin, ATRX, and DAXX. PanNECs are by definition high-grade tumors with highly aggressive clinical behavior, while PanNETs have a variable prognosis that is difficult to predict using current biomarkers such as tumor grade and size. Several studies have shown that ATRX or DAXX loss is strongly associated with a higher risk of PanNET metastasis and recurrence. They are therefore key prognostic markers in PanNETs. In addition, chromosomal copy number variations can further help assess PanNET aggressiveness and prognosis. Molecular profiling is increasingly important for improving the diagnosis, treatment, and prognosis of PanNENs.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Report of the German Society for Pathology Working Group on Hematopathology].","authors":"Sylvia Hartmann","doi":"10.1007/s00292-024-01389-4","DOIUrl":"10.1007/s00292-024-01389-4","url":null,"abstract":"","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging homologous recombination deficiency for sarcoma : Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma.","authors":"Lara Planas-Paz, Chantal Pauli","doi":"10.1007/s00292-024-01381-y","DOIUrl":"https://doi.org/10.1007/s00292-024-01381-y","url":null,"abstract":"<p><strong>Background: </strong>Homologous recombination deficiency (HRD) in tumors correlates with poor prognosis and metastases development. Determining HRD is of major clinical relevance as it can be treated with PARP inhibitors (PARPi). HRD remains poorly investigated in sarcoma, a rare and heterogeneous cancer of mesenchymal origin.</p><p><strong>Objective: </strong>We aimed (i) to investigate predictive biomarkers of HRD in several independent sarcoma cohorts using a cross-functional strategy by combining genomic, transcriptomic and phenotypic approaches and (ii) to evaluate the therapeutic potential of PARPi and DNA damage response (DDR)-based therapies ex vivo.</p><p><strong>Materials and methods: </strong>We performed a comprehensive genomic and transcriptomic characterization of sarcoma using datasets from The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and our own bone and soft tissue sarcoma cohorts. We evaluated PARP1/2 and WEE1 inhibition ex vivo in patient-derived sarcoma cell models as monotherapy and in combination with chemotherapeutic agents to identify synergistic effects.</p><p><strong>Results: </strong>Firstly, we identified genomic traits of HRD in a subset of sarcomas associated with molecular alterations in homologous recombination repair (HRR) pathway genes and high chromosomal instability. Secondly, we identified and validated distinct SARC-HRD transcriptional signatures that predicted sensitivity to PARPi. Finally, we showed functional defects in HRR in sarcoma cells that were associated with functional dependency towards PARPi and WEE1i and support the clinical use of RAD51 as a predictive biomarker for PARPi sensitivity.</p><p><strong>Conclusion: </strong>We provide a personalized oncological approach to potentially improve the treatment of sarcoma patients. We encourage the evaluation of gene expression signatures to enhance the identification of patients who might benefit from DDR-based therapies.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Next generation tissue biobanking: quality assured, financed, and integrated?]","authors":"Katja Steiger, Angela Langer, Alexander Brobeil","doi":"10.1007/s00292-024-01394-7","DOIUrl":"https://doi.org/10.1007/s00292-024-01394-7","url":null,"abstract":"<p><p>Biobanks are essential for biomedical research, particularly in the era of personalized medicine. In Germany, 36 biobanks have been established over the past decade that are connected under the German Biobank Alliance (GBA). These biobanks store high-quality biological samples along with clinical data to support research projects. Biobanks can be integrated, handling both tissue and liquid samples, or set up as separate entities depending on specific requirements.Tissue biobanking is especially complex due to the invasive nature of tissue collection and the non-replicability of the samples. Close collaboration between clinics, pathologists, IT specialists, and biobank managers is crucial to ensure the quality of samples and promote interdisciplinary research.The integration of pathology and biobanking is key, both organizationally and technically. Shared IT systems, standardized protocols, and collaborative governance structures are vital for efficient data management. Quality assurance, ethical guidelines, and data protection are critical to maintaining public trust and legal compliance.Long-term financial models are needed to ensure the sustainability of biobanks. The GBA supports emerging biobanks through its \"Starterkit\" initiative, offering guidance and best practices to help new biobanks develop.Tissue biobanks are indispensable for advancing the understanding of diseases and developing new therapies. However, they must adhere to strict ethical and legal standards to maximize their scientific and societal value.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Neuroendocrine carcinomas of the gastrointestinal tract : Morphology, molecular pathology, cellular origin].","authors":"Moritz Jesinghaus","doi":"10.1007/s00292-024-01386-7","DOIUrl":"https://doi.org/10.1007/s00292-024-01386-7","url":null,"abstract":"<p><p>Neuroendocrine carcinomas (NEC) are poorly differentiated neuroendocrine neoplasms that can occur ubiquitously in the mucosa-bearing organs of the gastrointestinal tract. Based on their morphology, they are classified into large cell (LCNEC) and small cell NEC (SCNEC). The most common form of mixed differentiation is the combination with an adenocarcinoma, referred to as mixed adenoneuroendocrine carcinoma (MANEC). NEC/MANEC exhibit a significantly poorer prognosis than the adenocarcinomas of their respective primary sites, which is inextricably linked to their typical histomorphology. Adenocarcinomas with aberrant expression of neuroendocrine markers do not show a worse clinical course. Molecularly, NEC/MANEC have a profile comparable to the adenocarcinomas of their site of origin and a profile divergent from neuroendocrine tumors. Analyses of gastric NEC/MANEC have shown frequent MYC amplifications, which are reflected in MYC signatures in various transcriptome analyses.The cellular origin of NEC remains a subject of controversial discussion. New insights are provided by a MYC-driven, genetically modified mouse model that led to the development of large gastric tumors. These tumors were histologically identified as LCNEC and were accompanied by both neuroendocrine and non-neuroendocrine precursor lesions. Using immunofluorescence, a derivation from resident neuroendocrine cells in the gastric corpus was demonstrated, suggesting that at least a portion of LCNEC may originate directly from neuroendocrine cells.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boolean network modeling and its integration with experimental read-outs : An interdisciplinary presentation using a leukemia model.","authors":"Julia Maier, Julian D Schwab, Silke D Werle, Ralf Marienfeld, Peter Möller, Nadine T Gaisa, Nensi Ikonomi, Hans A Kestler","doi":"10.1007/s00292-024-01395-6","DOIUrl":"https://doi.org/10.1007/s00292-024-01395-6","url":null,"abstract":"<p><p>The limited availability of suitable animal models and cell lines often impedes experimental cancer research. Wet-laboratory experiments are also time-consuming and cost-intensive. In this review, we present an in silico modeling strategy, namely, Boolean network (BN) models, and demonstrate how it could be applied to streamline experimental design and to focus the effort of experimental read-outs. Boolean network models allow for the dynamic analysis of large molecular signaling pathways and their crosstalks. After establishing and validating a specific tumor model, mechanistic insights into the tumor cell behavior can be gained by studying the trajectories of different tumor phenotypes. Also, tumor driver and drug target screenings can be performed. These automatic screenings can help to identify new intervention targets and putative biomarkers for tumor evolution, hence guiding new wet-laboratory experiments. The goal of this round-up is to demonstrate how to establish, validate, and use BN modeling and its crosstalks in classic wet-laboratory research using a chronic lymphocytic leukemia (CLL) BN model.</p>","PeriodicalId":74402,"journal":{"name":"Pathologie (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}