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  1. Article ; Online: Sliding Window Optimal Transport for Open World Artifact Detection in Histopathology.

    Fuchs, Moritz / Konstantin, Mirko / Schrade, Nicolas / Schweizer, Leonille / Tolkach, Yuri / Mukhopadhyay, Anirban

    IEEE journal of biomedical and health informatics

    2024  Volume PP

    Abstract: Histological images are frequently impaired by local artifacts from scanner malfunctions or iatrogenic processes - caused by preparation - impacting the performance of Deep Learning models. Models often struggle with the slightest out-of-distribution ... ...

    Abstract Histological images are frequently impaired by local artifacts from scanner malfunctions or iatrogenic processes - caused by preparation - impacting the performance of Deep Learning models. Models often struggle with the slightest out-of-distribution shifts, resulting in compromised performance. Detecting artifacts and failure modes of the models is crucial to ensure open-world applicability to whole slide images for tasks like segmentation or diagnosis. We introduce a novel technique for out-of-distribution detection within whole slide images, compatible with any segmentation or classification model. Our approach tiles multi-layer features into sliding window patches and leverages optimal transport to align them with recognized in-distribution samples. We average the optimal transport costs over tiles and layers to detect out-of-distribution samples. Notably, our method excels in identifying failure modes that would harm downstream performance, surpassing contemporary out-of-distribution detection techniques. We evaluate our method for both natural and synthetic artifacts, considering distribution shifts of various sizes and types. The results confirm that our technique outperforms alternative methods for artifact detection. We assess our method components and the ability to negate the impact of artifacts on the downstream tasks. Finally, we demonstrate that our method can mitigate the risk of performance drops in downstream tasks, enhancing reliability by up to 77%. In testing 7 annotated whole slide images with natural artifacts, our method boosted the Dice score by 68%, highlighting its real open-world utility.
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2695320-1
    ISSN 2168-2208 ; 2168-2194
    ISSN (online) 2168-2208
    ISSN 2168-2194
    DOI 10.1109/JBHI.2024.3383590
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book ; Online ; Thesis: Abhängigkeit des progressionsfreien Überlebens von der Histologie und Lokalisation der Lymphknoten bei Salvage-Lymphadenektomie nach radikaler Prostatektomie

    Langerenken, Anna-Katharina [Verfasser] / Pfister, David [Gutachter] / Tolkach, Yuri [Gutachter]

    2023  

    Author's details Anna-Katharina Langerenken ; Gutachter: David Pfister, Yuri Tolkach
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language German
    Publisher Universitäts- und Stadtbibliothek Köln
    Publishing place Köln
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  3. Article ; Online: Cystic Pelvic Masses in Men: A Presentation of Uncommon Cases and a Literature Review.

    Rieger, Constantin / Pfister, David / Kastner, Lucas / Eich, Marie-Lisa / Quaas, Alexander / Tolkach, Yuri / Heidenreich, Axel

    Clinical genitourinary cancer

    2024  Volume 22, Issue 2, Page(s) 523–534

    Abstract: Unclear cystic masses in the pelvis in male patients are a rare situation and could be of benign or malignant origin. The underlying diseases demand for specific diagnostic and therapeutic approaches. We present a case series of 3 male patients with ... ...

    Abstract Unclear cystic masses in the pelvis in male patients are a rare situation and could be of benign or malignant origin. The underlying diseases demand for specific diagnostic and therapeutic approaches. We present a case series of 3 male patients with different clinical symptoms (perineal pain, urinary retention and a large scrotal cyst) related to cystic lesions in the pelvic region. On all patients initial histopathological workup was unclear. All patients underwent surgery with complete resection of the tumor which revealed a broad spectrum of histopathological findings: unusual form of cystic adenocarcinoma of the prostate, malignant transformation of a dysontogenetic cyst, and finally a very rare diagnosis of a malignant tumor of the Cowper gland. This case series and literature review provide clues for a possible diagnostic and therapeutic approach in the case of unclear pelvic cystic masses and could support urologists during the therapy selection in the future.
    MeSH term(s) Humans ; Male ; Cysts/surgery ; Cysts/pathology ; Adenocarcinoma ; Pelvis/pathology ; Prostate/pathology ; Skin Neoplasms
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 2225121-2
    ISSN 1938-0682 ; 1558-7673
    ISSN (online) 1938-0682
    ISSN 1558-7673
    DOI 10.1016/j.clgc.2024.01.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cribriform and glomeruloid acinar adenocarcinoma of the prostate-an intratumoural intraductal carcinoma?

    Tolkach, Yuri / Kristiansen, Glen

    Histopathology

    2019  Volume 74, Issue 6, Page(s) 804–808

    MeSH term(s) Adenocarcinoma/pathology ; Carcinoma, Acinar Cell/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Humans ; Male ; Prostate/pathology ; Prostatic Neoplasms/pathology
    Language English
    Publishing date 2019-04-22
    Publishing country England
    Document type Editorial
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/his.13821
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Rasch wachsender, hochvaskularisierter Oberlidtumor.

    Schatten, Hannah / Gaca, Piotr Jakub / Tolkach, Yuri / Heindl, Ludwig M / Doulis, Alexandros E

    Die Ophthalmologie

    2022  Volume 120, Issue 9, Page(s) 954–956

    Title translation Rapidly growing, highly vascularized upper eyelid tumor.
    MeSH term(s) Humans ; Eyelid Neoplasms/surgery ; Eyelids/surgery
    Language German
    Publishing date 2022-12-06
    Publishing country Germany
    Document type Journal Article
    ISSN 2731-7218
    ISSN (online) 2731-7218
    DOI 10.1007/s00347-022-01767-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The Heterogeneity of Prostate Cancer: A Practical Approach.

    Tolkach, Yuri / Kristiansen, Glen

    Pathobiology : journal of immunopathology, molecular and cellular biology

    2018  Volume 85, Issue 1-2, Page(s) 108–116

    Abstract: Prostate cancer is a paradigm tumor model for heterogeneity in almost every sense. Its clinical, spatial, and morphological heterogeneity divided by the high-level molecular genetic diversity outline the complexity of this disease in the clinical and ... ...

    Abstract Prostate cancer is a paradigm tumor model for heterogeneity in almost every sense. Its clinical, spatial, and morphological heterogeneity divided by the high-level molecular genetic diversity outline the complexity of this disease in the clinical and research settings. In this review, we summarize the main aspects of prostate cancer heterogeneity at different levels, with special attention given to the spatial heterogeneity within the prostate, and to the standard morphological heterogeneity, with respect to tumor grading and modern classifications. We also cover the complex issue of molecular genetic heterogeneity, discussing it in the context of the current evidence of the genetic characterization of prostate carcinoma; the interpatient, intertumoral (multifocal disease), and intratumoral heterogeneity; tumor clonality; and metastatic disease. Clinical and research implications are summarized and serve to address the most pertinent problems stemming from the extreme heterogeneity of prostate cancer.
    MeSH term(s) Clonal Evolution ; Genetic Heterogeneity ; Humans ; Male ; Neoplasm Grading ; Neoplasm Metastasis ; Prostatic Neoplasms/classification ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology
    Language English
    Publishing date 2018-01-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1022703-9
    ISSN 1423-0291 ; 1015-2008
    ISSN (online) 1423-0291
    ISSN 1015-2008
    DOI 10.1159/000477852
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: An overview of translational prostate cancer cohorts for prognostic and predictive studies.

    Tolkach, Yuri / Kristiansen, Glen

    Histopathology

    2018  Volume 74, Issue 1, Page(s) 161–170

    Abstract: The aim of this review is to describe the characteristics of patient cohorts commonly used for translational biomarker research in prostate cancer and to outline the most prominent contemporary cohorts which serve as a source of prognostic and predictive ...

    Abstract The aim of this review is to describe the characteristics of patient cohorts commonly used for translational biomarker research in prostate cancer and to outline the most prominent contemporary cohorts which serve as a source of prognostic and predictive biomarkers. A non-systematic review of the literature was performed to identify and summarise well-characterized translational prostate cancer cohorts that provide state-of-the-art characterization of (i) primary and (ii) metastatic and castration-resistant prostate cancer. The main advantages and features of these cohorts are a substantial number of patients, unique patient groups, comprehensive genetic characterisation of tumours using multi-omics/next-generation sequencing approaches, high-quality control standards and fully or partially open data for the research community. This overview includes the contemporary cohorts which serve as a rich source of new targets for prognostic and predictive biomarkers as well as a reference database for validation of known biomarkers, therefore representing the cohorts whose impact extends over the current state of biomarker research into the near future (5-10 years).
    MeSH term(s) Biomarkers, Tumor/analysis ; Cohort Studies ; Humans ; Male ; Prognosis ; Prostatic Neoplasms ; Translational Medical Research
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2018-12-18
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/his.13770
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Targeted Therapy in Patients with Metastatic Male Germ Cell Tumors.

    Heidenreich, Axel / Paffenholz, Pia / Nestler, Tim / Tolkach, Yuri / Pfister, David

    Urologia internationalis

    2021  Volume 105, Issue 7-8, Page(s) 720–723

    Abstract: Ten to fifteen percent of patients with metastatic testis cancer (mGCT) will develop chemorefractory disease of which about 50% will die. We report on the integration of next generation sequencing in daily clinical practice to identify druggable ... ...

    Abstract Ten to fifteen percent of patients with metastatic testis cancer (mGCT) will develop chemorefractory disease of which about 50% will die. We report on the integration of next generation sequencing in daily clinical practice to identify druggable mutations in metastatic lesions of 3 patients with mGCT. Mutational analysis revealed KIT D820G, TP53, and NPM1 mutations as well as mismatch repair deficiency with loss of MSH2 and MSH6 proteins so that targeted therapy with sunitinib (n = 2) or pembrolizumab (n = 1) was initiated resulting in remarkable partial remissions for 9, 12+, and 15 months.
    MeSH term(s) Adult ; Aged ; Humans ; Male ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal/drug therapy ; Neoplasms, Germ Cell and Embryonal/pathology ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/pathology
    Language English
    Publishing date 2021-03-17
    Publishing country Switzerland
    Document type Case Reports ; Journal Article
    ZDB-ID 204045-1
    ISSN 1423-0399 ; 0042-1138
    ISSN (online) 1423-0399
    ISSN 0042-1138
    DOI 10.1159/000510717
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Is high-grade prostatic intraepithelial neoplasia (HGPIN) a reliable precursor for prostate carcinoma? Implications for clonal evolution and early detection strategies.

    Tolkach, Yuri / Kristiansen, Glen

    The Journal of pathology

    2018  Volume 244, Issue 4, Page(s) 389–393

    Abstract: High-grade prostatic intraepithelial neoplasia (HGPIN) is a documented putative precursor lesion for invasive prostate adenocarcinoma. However, the precise mechanisms of the carcinoma's development from HGPIN are unclear. Many studies have attempted a ... ...

    Abstract High-grade prostatic intraepithelial neoplasia (HGPIN) is a documented putative precursor lesion for invasive prostate adenocarcinoma. However, the precise mechanisms of the carcinoma's development from HGPIN are unclear. Many studies have attempted a comparative molecular genetic characterisation of HGPIN and its corresponding carcinoma to study this transformation. However, to date, some HGPIN mimickers, such as intraductal carcinoma, which can engage in retrograde colonisation of the prostatic acini in an HGPIN-like manner, have been described. In this work, we hypothesise that the lesion formerly known as HGPIN adjacent to invasive carcinoma does not necessarily represent its respective precursor lesion. This hypothesis stems from recent morphological, experimental, and theoretical evidence on the development of tumour clonality, as well as recent studies outlining the three-dimensional architecture of prostate adenocarcinomas (most importantly, their interconnection with the tumoural glandular system). Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    MeSH term(s) Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Biomarkers, Tumor/genetics ; Biopsy ; Clonal Evolution ; Disease Progression ; Early Detection of Cancer/methods ; Genetic Predisposition to Disease ; Humans ; Male ; Neoplasm Grading ; Phenotype ; Predictive Value of Tests ; Prostatic Intraepithelial Neoplasia/genetics ; Prostatic Intraepithelial Neoplasia/pathology ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2018-03-07
    Publishing country England
    Document type Journal Article ; Video-Audio Media
    ZDB-ID 3119-7
    ISSN 1096-9896 ; 0022-3417
    ISSN (online) 1096-9896
    ISSN 0022-3417
    DOI 10.1002/path.5045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Intratumoral Abundance of M2-Macrophages is Associated With Unfavorable Prognosis and Markers of T-Cell Exhaustion in Small Cell Lung Cancer Patients.

    Klein, Sebastian / Schulte, Annalena / Arolt, Christoph / Tolkach, Yuri / Reinhardt, Hans Christian / Buettner, Reinhard / Quaas, Alexander

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

    2023  Volume 36, Issue 10, Page(s) 100272

    Abstract: Small cell lung cancer (SCLC) accounts for about 10% to 15% of lung cancer cases. Unlike non-SCLC, therapy options for SCLC are limited, reflected by a 5-year survival rate of about 7%. At the same time, the rise of immunotherapeutic approaches in cancer ...

    Abstract Small cell lung cancer (SCLC) accounts for about 10% to 15% of lung cancer cases. Unlike non-SCLC, therapy options for SCLC are limited, reflected by a 5-year survival rate of about 7%. At the same time, the rise of immunotherapeutic approaches in cancer therapy has rationalized to account for inflammatory phenotypes in tumors. However, the composition of the inflammatory microenvironment in human SCLC is poorly understood to date. In our study, we used in-depth image analysis of virtual whole-slide-images of 45 SCLC tumors and evaluated different markers of M2-macrophages (CD163 and CD204) together with global immunologic markers (CD4, CD8, CD68, CD38, FOXP3, and CD20) and characterized their abundance intratumorally using quantitative image analysis, combined with a deep-learning model for tumor segmentation. In addition, independent scoring, blinded to the results of the computational analysis, was performed by an expert pathologist (A.Q.) of both CD163/CD204 and PD-L1. To this end, we evaluated the prognostic relevance of the abundance of these cell types to overall survival. Given a 2-tier threshold of the median of the M2 marker CD163 within the study population, there was a 12-month overall survival rate of 22% (95% CI, 10%-47%) for patients with high CD163 abundance and 41% (95% CI, 25%-68%) for patients with low CD163 counts. Patients with increased CD163 had a median overall survival of 3 months compared to 8.34 months for patients with decreased CD163 counts (P = .039), which could be confirmed by an expert pathologist (A.Q., P = .018). By analyzing cases with increased CD163 cell infiltrates, a trend for higher FOXP3 counts and PD-L1 positive cells, together with increased CD8 T-cell infiltrates, was observed, which could be confirmed using an independent cohort at the transcriptional level. Together, we showed that markers of M2 were associated with unfavorable outcome in our study cohort.
    Language English
    Publishing date 2023-07-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645073-8
    ISSN 1530-0285 ; 0893-3952
    ISSN (online) 1530-0285
    ISSN 0893-3952
    DOI 10.1016/j.modpat.2023.100272
    Database MEDical Literature Analysis and Retrieval System OnLINE

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