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Article ; Online: Mitotic activity: A systematic literature review of the assessment methodology and prognostic value in feline tumors.

Bertram, Christof A / Donovan, Taryn A / Bartel, Alexander

2024 , Page(s) 3009858241239566

Abstract: Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an analysis of all available references on mitotic activity in feline tumors to provide an ... ...

Abstract	Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an analysis of all available references on mitotic activity in feline tumors to provide an overview of the assessment methods and prognostic value. A systematic literature search in PubMed and Scopus and a nonsystematic search in Google Scholar were conducted. All articles on feline tumors that correlated mitotic activity with patient outcome were identified. Data analysis revealed that of the 42 eligible articles, mitotic count (MC, mitotic figures/tumor area) was evaluated in 39 studies, and mitotic index (MI, mitotic figures/tumor cells) in 3 studies. The risk of bias was considered high for most studies (26/42, 62%) based on small study populations, insufficient details of the MC/MI methods, and lack of statistical measures for diagnostic accuracy or effect on outcome. The MC/MI methods varied between studies. A significant association of MC with survival was determined in 20 of 28 (71%) studies (10 studies evaluated other outcome metrics or provided individual patient data), while 1 study found an inverse effect. Three tumor types had at least 4 studies, and a prognostic association with survival was found in 5 of 6 studies on mast cell tumors, 5 of 5 on mammary tumors, and 3 of 4 on soft-tissue sarcomas. MI was shown to correlate with survival for mammary tumors by 2 research groups; however, comparisons to MC were not conducted. Further studies with standardized mitotic activity methods and appropriate statistical analysis for discriminant ability of patient outcome are needed to infer the prognostic value of MC and MI.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/03009858241239566
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Article ; Online: Mitotic activity: A systematic literature review of the assessment methodology and prognostic value in canine tumors.

Bertram, Christof A / Donovan, Taryn A / Bartel, Alexander

Veterinary pathology

2024 , Page(s) 3009858241239565

Abstract: One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review was to analyze the methods and prognostic relevance of ...

Abstract	One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review was to analyze the methods and prognostic relevance of histologically measuring mitotic activity that have been reported for canine tumors in the literature. A total of 137 articles that correlated the mitotic activity in canine tumors with patient outcome were identified through a systematic (PubMed and Scopus) and nonsystematic (Google Scholar) literature search and eligibility screening process. Mitotic activity methods encompassed the mitotic count (MC, number of mitotic figures per tumor area) in 126 studies, presumably the MC (method not specified) in 6 studies, and the mitotic index (MI, number of mitotic figures per number of tumor cells) in 5 studies. A particularly high risk of bias was identified based on the available details of the MC methods and statistical analyses, which often did not quantify the prognostic discriminative ability of the MC and only reported
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/03009858241239565
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors.

Bertram, Christof A / Bartel, Alexander / Donovan, Taryn A / Kiupel, Matti

Veterinary sciences

2023 Volume 11, Issue 1

Abstract: Cell division through mitosis (microscopically visible as mitotic figures, MFs) is a highly regulated process. However, neoplastic cells may exhibit errors in chromosome segregation (microscopically visible as atypical mitotic figures, AMFs) resulting in ...

Abstract	Cell division through mitosis (microscopically visible as mitotic figures, MFs) is a highly regulated process. However, neoplastic cells may exhibit errors in chromosome segregation (microscopically visible as atypical mitotic figures, AMFs) resulting in aberrant chromosome structures. AMFs have been shown to be of prognostic relevance for some neoplasms in humans but not in animals. In this study, the prognostic relevance of AMFs was evaluated for canine cutaneous mast cell tumors (ccMCT). Histological examination was conducted by one pathologist in whole slide images of 96 cases of ccMCT with a known survival time. Tumor-related death occurred in 11/18 high-grade and 2/78 low-grade cases (2011 two-tier system). The area under the curve (AUC) was 0.859 for the AMF count and 0.880 for the AMF to MF ratio with regard to tumor-related mortality. In comparison, the AUC for the mitotic count was 0.885. Based on our data, a prognostically meaningful threshold of ≥3 per 2.37 mm
Language	English
Publishing date	2023-12-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2768971-2
ISSN	2306-7381 ; 2306-7381
ISSN (online)	2306-7381
ISSN	2306-7381
DOI	10.3390/vetsci11010005
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Book ; Online: Systematic Review of Methods and Prognostic Value of Mitotic Activity. Part 2

Bertram, Christof A. / Donovan, Taryn A. / Bartel, Alexander

Canine Tumors

2023

Abstract: One of the most relevant prognostication tests for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review is to scholarly analyze the methods and prognostic ... ...

Abstract	One of the most relevant prognostication tests for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review is to scholarly analyze the methods and prognostic relevance of histologically measuring mitotic activity in canine tumors. A total of 137 articles that correlated the mitotic activity in canine tumors with patient outcome were identified through a systematic (PubMed and Scopus) and manual (Google Scholar) literature search and eligibility screening process. These studies determined the mitotic count (MC, number of mitotic figures per tumor area) in 126 instances, presumably the mitotic count (method not specified) in 6 instances and the mitotic index (MI, proportion of mitotic figures per tumor cells) in 5 instances. A particularly high risk of bias was identified in the available details of the MC methods and statistical analysis, which often did not quantify the prognostic discriminative ability of the MC and only reported p-values. A significant association of the MC with survival was found in 72/109 (66%) studies. However, survival was evaluated by at least three studies in only 7 tumor types/groups, of which a prognostic relevance is apparent for mast cell tumors of the skin, cutaneous melanoma and soft tissue sarcoma of the skin. None of the studies on the MI found a prognostic relevance. Further studies on the MC and MI with standardized methods are needed to prove the prognostic benefit of this test for further tumor types.
Keywords	Quantitative Biology - Subcellular Processes ; Quantitative Biology - Tissues and Organs
Subject code	571
Publishing date	2023-05-31
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Systematic Review of Methods and Prognostic Value of Mitotic Activity. Part 1

Bertram, Christof A. / Donovan, Taryn A. / Bartel, Alexander

Feline Tumors

2023

Abstract: Increased proliferation is a key driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. The goal of this systematic review is scholarly analysis of all available references on mitotic activity in feline ... ...

Abstract	Increased proliferation is a key driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. The goal of this systematic review is scholarly analysis of all available references on mitotic activity in feline tumors, and to provide an overview of the measuring methods and prognostic value. A systematic literature search in PubMed and Scopus and a manual search in Google Scholar was conducted. All articles on feline tumors that correlated mitotic activity with patient outcome were identified. Data analysis revealed that of the eligible 42 articles, the mitotic count (MC, mitotic figures per tumor area) was evaluated in 39 instances and the mitotic index (MI, mitotic figures per tumor cells) in three instances. The risk of bias was considered high for most studies (26/42, 62%) based on small study populations, insufficient details of the MC/MI methods, and lack of statistical measures for diagnostic accuracy or effect on outcome. The MC/MI methods varied markedly between studies. A significant association of the MC with survival was determined in 21/29 (72%) studies, while one study found an inverse effect. There were three tumor types with at least four studies and a prognostic association was found in 5/6 studies on mast cell tumors, 5/5 on mammary tumors and 3/4 on soft tissue sarcomas. The MI was shown to correlate with survival by two research groups, however a comparison to the MC was not conducted. An updated systematic review will be needed with of new literature for different tumor types.
Keywords	Quantitative Biology - Subcellular Processes
Subject code	571
Publishing date	2023-05-02
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Retrobulbar Adenocarcinoma with Subconjunctival Extension in a Common Buzzard (

Bertram, Christof A / Halter, Lesley / Feyer, Sina / Klopfleisch, Robert / Müller, Kerstin

Journal of avian medicine and surgery

2022 Volume 36, Issue 1, Page(s) 78–84

Abstract: A free ranging, fledged common buzzard ( ...

Abstract	A free ranging, fledged common buzzard (
MeSH term(s)	Adenocarcinoma/veterinary ; Animals ; Birds ; Eye ; Falconiformes ; Orbit
Language	English
Publishing date	2022-05-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2174190-6
ISSN	1938-2871 ; 1082-6742
ISSN (online)	1938-2871
ISSN	1082-6742
DOI	10.1647/20-00073
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Article ; Online: Histological classification of canine and feline lymphoma using a modular approach based on deep learning and advanced image processing.

Haghofer, Andreas / Fuchs-Baumgartinger, Andrea / Lipnik, Karoline / Klopfleisch, Robert / Aubreville, Marc / Scharinger, Josef / Weissenböck, Herbert / Winkler, Stephan M / Bertram, Christof A

Scientific reports

2023 Volume 13, Issue 1, Page(s) 19436

Abstract: Histopathological examination of tissue samples is essential for identifying tumor malignancy and the diagnosis of different types of tumor. In the case of lymphoma classification, nuclear size of the neoplastic lymphocytes is one of the key features to ... ...

Abstract	Histopathological examination of tissue samples is essential for identifying tumor malignancy and the diagnosis of different types of tumor. In the case of lymphoma classification, nuclear size of the neoplastic lymphocytes is one of the key features to differentiate the different subtypes. Based on the combination of artificial intelligence and advanced image processing, we provide a workflow for the classification of lymphoma with regards to their nuclear size (small, intermediate, and large). As the baseline for our workflow testing, we use a Unet++ model trained on histological images of canine lymphoma with individually labeled nuclei. As an alternative to the Unet++, we also used a publicly available pre-trained and unmodified instance segmentation model called Stardist to demonstrate that our modular classification workflow can be combined with different types of segmentation models if they can provide proper nuclei segmentation. Subsequent to nuclear segmentation, we optimize algorithmic parameters for accurate classification of nuclear size using a newly derived reference size and final image classification based on a pathologists-derived ground truth. Our image classification module achieves a classification accuracy of up to 92% on canine lymphoma data. Compared to the accuracy ranging from 66.67 to 84% achieved using measurements provided by three individual pathologists, our algorithm provides a higher accuracy level and reproducible results. Our workflow also demonstrates a high transferability to feline lymphoma, as shown by its accuracy of up to 84.21%, even though our workflow was not optimized for feline lymphoma images. By determining the nuclear size distribution in tumor areas, our workflow can assist pathologists in subtyping lymphoma based on the nuclei size and potentially improve reproducibility. Our proposed approach is modular and comprehensible, thus allowing adaptation for specific tasks and increasing the users' trust in computer-assisted image classification.
MeSH term(s)	Animals ; Dogs ; Cats ; Artificial Intelligence ; Deep Learning ; Reproducibility of Results ; Cat Diseases/diagnostic imaging ; Dog Diseases/diagnostic imaging ; Image Processing, Computer-Assisted/methods ; Lymphoma/diagnostic imaging ; Lymphoma/veterinary
Language	English
Publishing date	2023-11-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-46607-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Pathologist 2.0: An Update on Digital Pathology in Veterinary Medicine.

Bertram, Christof A / Klopfleisch, Robert

Veterinary pathology

2017 Volume 54, Issue 5, Page(s) 756–766

Abstract: Using light microscopy to describe the microarchitecture of normal and diseased tissues has changed very little since the middle of the 19th century. While the premise of histologic analysis remains intact, our relationship with the microscope is ... ...

Abstract	Using light microscopy to describe the microarchitecture of normal and diseased tissues has changed very little since the middle of the 19th century. While the premise of histologic analysis remains intact, our relationship with the microscope is changing dramatically. Digital pathology offers new forms of visualization, and delivery of images is facilitated in unprecedented ways. This new technology can untether us entirely from our light microscopes, with many pathologists already performing their jobs using virtual microscopy. Several veterinary colleges have integrated virtual microscopy in their curriculum, and some diagnostic histopathology labs are switching to virtual microscopy as their main tool for the assessment of histologic specimens. Considering recent technical advancements of slide scanner and viewing software, digital pathology should now be considered a serious alternative to traditional light microscopy. This review therefore intends to give an overview of the current digital pathology technologies and their potential in all fields of veterinary pathology (ie, research, diagnostic service, and education). A future integration of digital pathology in the veterinary pathologist's workflow seems to be inevitable, and therefore it is proposed that trainees should be taught in digital pathology to keep up with the unavoidable digitization of the profession.
Language	English
Publishing date	2017-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/0300985817709888
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Fine needle aspirate of an intestine-associated mass in a domestic rabbit (Oryctolagus cuniculus)

Bertram, Christof A / Klopfleisch, Robert / Müller, Kerstin

Journal of exotic pet medicine. 2019 Oct., v. 31

2019

Abstract: Smears of a fine needle aspirate of an abdominal, intestine-associated mass in a domestic rabbit revealed abundant polymorphous cocci and rod-shaped bacteria, as well as plant material in one location. Cell structures were largely necrotic; however, some ...

Abstract	Smears of a fine needle aspirate of an abdominal, intestine-associated mass in a domestic rabbit revealed abundant polymorphous cocci and rod-shaped bacteria, as well as plant material in one location. Cell structures were largely necrotic; however, some cells were consistent with mainly degenerated heterophils. Cytopathological differential diagnosis included a small intestinal pseudodiverticulum with secondary inflammation and an intestine-associated abscess. Histopathological examination confirmed an ileal pseudodiverticulum with severe inflammation.
Keywords	Oryctolagus cuniculus ; abscess ; bacteria ; cell structures ; heterophils ; histopathology ; ileum ; rabbits
Language	English
Dates of publication	2019-10
Size	p. 61-63.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2228614-7
ISSN	1557-5063
ISSN	1557-5063
DOI	10.1053/j.jepm.2019.04.015
Database	NAL-Catalogue (AGRICOLA)

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Article: Tracheal and Laryngeal Tumors in Two Domestic Rabbits (Orytolagus Cuniculus)

Bertram, Christof A / Klopfleisch, Robert / Müller, Kerstin

Journal of exotic pet medicine. 2019 Apr., v. 29

2019

Abstract: Dyspnea is a very common clinical finding in rabbits and is often associated with infection of the respiratory tract or cranial mediastinal tumors. Airway obstruction as a cause of dyspnea has been very rarely reported to date. Here, 2 cases of airway ... ...

Abstract	Dyspnea is a very common clinical finding in rabbits and is often associated with infection of the respiratory tract or cranial mediastinal tumors. Airway obstruction as a cause of dyspnea has been very rarely reported to date. Here, 2 cases of airway tumors in a 4-year old and 4.5-year old rabbit, respectively, are described. Clinically, airway tumors of both patients were associated with progressive dyspnea that was initially considered to be caused by bacterial upper airway obstruction; however antimicrobial treatment was unrewarding. In case 1, a radiographic and computed tomographic examination revealed an intraluminal soft tissue-opaque mass in the thoracic trachea at the level of the first and second thoracic vertebrae. Surgical excision was considered to be difficult due to the intrathoracic location and the owner elected for humane euthanasia. A subsequent histopathological examination of the tracheal mass revealed that the mass was located in the tunica mucosa and exophytically protruded into the tracheal lumen. Immunohistochemically, tumors cells were positive for cytokeratin and negative for vimentin, which supports the histopathologic diagnosis of a tracheal adenocarcinoma. In case 2, clinical examination and thoracic radiography did not reveal an airway obstruction. Postmortem examination identified a laryngeal osteochondroma largely obstructing the laryngeal lumen. Both, laryngeal and tracheal neoplasia, should be considered as an uncommon cause of progressive dyspnea that is nonresponsive to antimicrobial treatment. Besides radiography and computed tomography, the authors recommend endoscopy as an ideal diagnostic tool to identify airway obstruction.
Keywords	Petrorhagia ; adenocarcinoma ; clinical examination ; computed tomography ; dyspnea ; endoscopy ; euthanasia ; excision ; histopathology ; immunohistochemistry ; larynx ; mucosa ; necropsy ; patients ; rabbits ; radiography ; vertebrae ; vimentin
Language	English
Dates of publication	2019-04
Size	p. 142-146.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2228614-7
ISSN	1557-5063
ISSN	1557-5063
DOI	10.1053/j.jepm.2018.08.007
Database	NAL-Catalogue (AGRICOLA)

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