2024-03-29T04:53:55Z
http://www.diagnosticpathology.eu/content/index.php/dpath/oai
oai:ojs2.localhost:article/109
2019-08-22T16:01:36Z
dpath:RES
"160628 2016 eng "
2364-4893
dc
A sustainable visual representation of available histopathological digital knowledge for breast cancer grading
Traore, Lamine
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris 13, Sorbonne Paris Cité, Laboratoire d’Informatique Médicale et Ingénierie des Connaissances en eSanté (LIMICS UMR_S 1142)
Daniel, Christel
Assistance Publique-Hôpitaux de Paris (AP-HP), CCS SI Patient, Paris, France
Jaulent, Marie-Christine
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris 13, Sorbonne Paris Cité, Laboratoire d’Informatique Médicale et Ingénierie des Connaissances en eSanté (LIMICS - UMR_S 1142), 15 rue de l’école de médecine, Paris, France
Schrader, Thomas
University of Applied Sciences Brandenburg Magdeburger, Department Informatics and Media, Brandenburg, Germany
Racoceanu, Daniel
Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Laboratoire d’Imagerie Biomédicale (LIB), 75013, Paris, France
Kergosien, Yannick
Département d’Informatique Université de Cergy-Pontoise, Cergy-Pontoise, France
Breast cancer grading, semantic annotation, knowledge formalization and modeling, standardization, computer aided diagnosis, high-content image exploration, digital pathology
Background: Recently, anatomic pathology (AP) has seen the introduction of several tools such as slide scanners and virtual slide technologies, creating the conditions for broader adoption of computer aided diagnosis based on whole slide images (WSI). This change brings up a number of new scientific challenges such as the sustainable management of the explicit and unambiguous semantics associated to the diagnostic interpretation of AP images by both humans (pathologists) and computers (image analysis algorithms) . In order to reduce inter-observer variability between AP reports of malignant tumors, the College of American Pathologists edited more than 60 organ-specific Cancer Checklists and associated Protocols (CAP-CC&P). Each checklist includes a set of AP observations that are expected to be reported by pathologists in organ-specific AP cancer reports. Our objective was to i) identify the available histopathological formalized knowledge from NCBO Bioportal and UMLS metathesaurus in the scope of the CAP CC&P for breast cancer grading and ii) to build a sustainable visual representation of this knowledge using UMLS semantic types.
Methods: Our methodology was applied on the two breast cancer CAP-CC&Ps dedicated to invasive carcinoma (IC) and ductal carcinoma in situ (DCIS). We focused on a subset of quantifiable AP observations of the CAP-CCs - i.e. observable entities that could be computed by image analysis tools and on the corresponding notes in the protocols that unambiguously describe how pathologists should derive a high-level observation (e.g. Nottingham score) from low-level morphological characteristics observed in images (e.g. mitotic count or glandular/tubular differentiation).The notes were annotated manually by two AP experts (gold standard) and automatically by NCBO Annotator using the 508 ontologies available on the NCBO platform. A sub-set of reference ontologies was selected based on their capacities to automatically identify concepts in the notes and compared to the subset of ontologies selected based on their capacity to identify the concepts identified by experts (gold standard). Once automatically extracted from the notes, the concepts belonging to different ontologies, were integrated into a unique graph and organized according to UMLS semantic types.
Results: The most relevant biomedical ontologies to be used for the annotation of the notes describing quantifiable observable entities of breast cancer CAP-CC&Ps are SNOMED-CT, LOINC, NCIT, NCI CaDSR Value Sets and PathLex. A visual representation integrating 25 concepts from the 5 different ontologies organized according to 11 UMLS semantic types was built to support AP experts for building a formal representation of the low-level quantifiable entities automatically extracted from the CAP-CC&Ps notes.
Conclusion: The proposed approach and tools, based on the CAP-CC&Ps, aim at supporting AP experts in building a standard-based representation of low-level morphological abnormalities observed in cancer that can be quantified using image analysis tools. This effort is complementary to the Integrating the Healthcare Enterprise (IHE) initiative building a standard-based representation of high-level AP observations required in cancer AP reports. Additional efforts are needed to achieve a workable standard-based formal representation of histopathological knowledge integrating both observable entities reported by humans (pathologists) and quantifiable entities automatically computed by machines. Providing such unique formal representation paves the way for more efficient use of computer aided diagnosis in AP as well as for the development of new biomarkers based on automatic analysis of whole slide images (WSI).
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/109
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/253
2019-08-22T15:37:30Z
dpath:RES
"171228 2017 eng "
2364-4893
dc
Cytology consultations with associated image quality evaluation – experiences of the Virtual International Pathology Institute (VIPI)
Kayser, Gian
Institute of Pathology, University of Freiburg, Freiburg, Germany
Borkenfeld, Stephan
International Academy of Telepathology, Heidelberg, Germany
Ayad, Essam
Institute of Pathology, Cairo University, Cairo, Egypt
Djenouni, Armina
Institute of Cytology and Pathology, Batna, Algeria
Mariamidze, Armaz
Institute of Pathology, National Cancer Center, Tblisi, Georgia
Mkhitaryan, Armen
HistoGen, Armenian-German Practical Scientific Center of Pathology, Yerevan, Armenia
Kayser, Klaus
Institute of Pathology, Charite, Berlin, Germany
Background: The virtual international Pathology Institute (VIPI, www.diagnomx.eu/vipi) is the only image consultation forum that is organized in close organization to a conventional institute of pathology. Its approximately 160 experts in pathology and cytology consult and diagnose difficult cases on the basis of a convent weekly duty plan. Herein we report the consultation results of a specific series of cytology specimens, and discuss potential application in routine virtual cytology.
Material and Methods: Still images of fine needle aspirations sent for consultation to VIPI were evaluated by five members of VIPI. A total of forty and seven cases was analyzed, and scored in four classes (benign, probably benign, probably malignant, and malignant). In addition, the consultants evaluated and graded their impression of colour, focus and general image quality in 10 classes (10 = very good <> 1 = not acceptable). Automated measurements of objective image quality, calculation of the regions of interest (ROI), and automated diagnosis classifications were performed too.
Results: The experts’ diagnostic conformity was computed 4.2/5; i.e., at average 4.2 experts stated the same diagnosis of each case. The automated classification supported the summarized experts’ diagnoses in 38/47 cases. The experts interpreted the image quality diversely. Two of them evaluated with tendency of low, and two of them of high grades. The individual interactive image quality evaluations showed statistically significant relationship to the diagnostic accuracy (p<0.05). A helpful and correct automated ROI detection was stated in more than 95% of images.
Conclusion: The study indicates that electronic transmission of acquired conventional cytology smears is a useful tool to get access to experts’ knowledge worldwide. The case related diagnostic agreement of experts can serve for gold standard of virtual cytology (for example conformity > 80%). Additional automated measurements might support the diagnosis. Implementation of virtual slide technology and automated ROI visualization are additional tools in order to support the diagnostic accuracy. Virtual international pathology institutions are able to successfully work together with or even replace conventional cytology laboratories.
DiagnomX GmbH
2017-02-09 12:31:05
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/253
Diagnostic Pathology; Vol 3 No 1 (2017): 2017
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/97
2018-06-19T09:04:46Z
dpath:RES
"151231 2015 eng "
2364-4893
dc
The concept of entropy in histopathological diagnosis and targeted therapy
Kayser, Klaus
Charite - Berlin
Borkenfeld, Stephan
Carvalho, Rita
Kayser, Gian
Background
Targeted therapy has been developed to apply individual patient – specific drug regimes that are based upon specific bio-chemical intra-cellular pathways and usually related to cellular proliferation or apoptosis.
Entropy Definition and ConceptÂ
Entropy is considered to be a physical entity similar to space and time. It quantifies the distribution of events and transport mechanisms in relation to the macrosystem for thermodynamic, chemical and biological processes which are analyzed by statistics, communication and information methods. It amounts the distance of a gross (macro) system from its final stage in heat theory; in biology the entropy flow measures its dynamics (distance from its environment) through the surface of an open macrosystem, for example of a society, an individual, an organ, a gene, cell, and others. A derivative of entropy is the so-called structural entropy that measures the distance of internal (enclosed) microstates in the macrosystem. It can be computed by quantification of internal (vascular) and external (outer) surfaces of solid tumors, and their proliferation.
Entropy and targeted TherapyÂ
The most frequently investigated pathways include onco and suppressor genes that display pathways with cellular surface receptors such as the epidermal growth factor receptor (EGFR), and others. The presence and signalling intensity of EFGR in a set of malignant tumors can be considered as microstate in a large compartment of the whole cancer (macrosystem). Thus entropy and structural entropy can measure and classify the internal dynamic structure of the investigated cancer and can be associated to the therapy response and patient’s survival.
ResultsÂ
The concept of entropy and structural entropy has been tested and applied on several cancer cell types including primary lung cancer and pulmonary metastases of colon cancer. The patients’ survival rates were closely associated with the corresponding entropies and entropy flows. These tests have been based upon visualization of proliferation (Ki-67). The extension of this entropy concept to be applied in targeted therapy of breast and lung cancer is under investigation.
ConclusionÂ
The concept of conventional and structural entropy is a promising tool in search for understanding biological structures and their related functions, for improved analysis of microstate dynamics in malignant tumors, and can serve for refinement of targeted therapy.Â
Â
DiagnomX GmbH
2015-01-08 17:32:29
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/97
Diagnostic Pathology; 2015
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/247
2019-08-22T15:53:44Z
dpath:RES
"170720 2017 eng "
2364-4893
dc
Regional variation of non-Hodgkin’s Lymphoma (NHL) in Mongolia and its association with Ki-67 expression
Dungubat, Erdenetsogt
National University of Medical Sciences (MNUMS)
Sharkhuu, Enkhtuya
Enkhba, Bayarmaa
Jamiyan, Tsengelmaa
Norov, Oyundelger
Lodon, Galtsog
Background: The prevalence of non-Hodgkin’s lymphoma (NHL) varies worldwide in association with demographic and environmental factors. The analysis of these associations in Asia, Africa, and less developed countries is limited by low absolute numbers and unknown etiologic factors such as in Mongolia. The geographic variations in NHL incidence and mortality rates may induce by differences in case ascertainment and registration, or disease diagnosis and classification. The interpretation of NHL patterns and trends remains difficult. Therefore, an attempt was made to test the correlation between Ki-67 expression and clinical parameters on one hand, and geographical or ethnic differences on the other.
Research purpose: The objectives of this study are to examine the geographic distribution of non-Hodgkin's disease more in detail for high incidence Mongolian prefectures, and to evaluate the association between the distribution of NHL and Ki-67 expression.
Methods: Expression of Ki-67 was examined using an immunohistochemical technique in archival paraffin-embedded sections taken from (n=35) both National pathology center of Mongolia and Etemo clinic previously. Geo-processing was conducted with the aide of the software R Studio [under the Mapping plots] (1.0.136 version). The analyzed geographic incidence rates of NHL include locations of the central and east provinces Orkhon, Uvurhangay, Khuvsgul, Ulaanbaatar and Dornod The age-specific incidence and mortality rates were compared to those for all regions in Mongolia and those for the combined high mortality localities within the high-risk prefectures.
Results: Expression of Ki-67 protein was noted in 71.8% of the tumor cases. Average Ki-67 expression was associated with regions of high incidence.
Conclusion: We found that provinces with a high incidence and mortality from non-Hodgkin's disease were aggregated in the eastern-central parts of Mongolia, particularly in the areas along Ulaanbaatar capital city.
DiagnomX GmbH
2017-02-09 12:31:05
application/pdf
application/xml
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/247
Diagnostic Pathology; Vol 3 No 1 (2017): 2017
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/3
2018-06-19T09:07:53Z
dpath:RES
"150331 2015 eng "
2364-4893
dc
Specificities of Electronic Publication in Medicine
Borkenfeld, Stephan
Kayser, Klaus
Open access publication; citation index; faked data; publication manufactories; globalization diagnostic pathology;
Background
Electronic Media are considered to be a useful tool to distribute scientific information in medicine. Starting in this century all main publishers use electronic information transfer and distribution, either solely by electronic media or in combination with conventional paper printing.
Theory
Information distribution and communication require a sender (author), a transport medium (visual or acoustic signals, telephone, radio, TV, printed journals), and a receiver (hearer, reader). Information distribution in science and medicine should permit an objective and non-biased understanding of the transferred information by the receiver (doctor). These actions should be repeatable in time and space. This aim is in contrast to emotional, business-oriented, or political information transfer that commonly wants to direct the receiver in a certain surge or emotion.
Implementation
Scientific, peer reviewed open access journals have been established since the beginning of this century. After a period of hesitation and resistance which lasted for about 10 years, now-a-days nearly all big publishing companies offer open access journals in their product line. Most of them still hold on paper printed journals in addition, others offer hybrid journals, i.e., paper printed information display contemporary with electronic distribution. The electronic structures differ from classic structures (different, subject oriented domains) to articles of different focus that are fully integrated in only one individual domain. The advantages and disadvantages of the different structures are discussed in detail.
Conclusions and perspectives
Information distribution and communication is one important issue of life. The progress of technology does not stop at the doors of research and practice in medicine. To the contrary, it promotes both, understanding, interpretation and innovation of research, and the practical application. These facilitations of promotion are accompanied by ease of falsification and faked data. Business models of open access publication open doors of temptations to undercut science by anticipated profit. Previously serious publishers are already spoiled, and the scientific community should be aware that global investors are already misusing modern communication in science and research for their profit interest.
DiagnomX GmbH
2015-01-08 17:32:29
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/3
Diagnostic Pathology; 2015
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/232
2018-06-19T08:55:24Z
dpath:RES
"161202 2016 eng "
2364-4893
dc
Research on Devices for Handling Whole Slide Images on Pathology Workstations. An Ergonomic Outlook
Alcaraz Mateos, Eduardo
Pathology Department, Morales Meseguer University Hospital, Murcia, Spain.
Caballero-Alemán, Fuensanta
Intensive Care Unit. Morales Meseguer University Hospital, Murcia, Spain.
AlbarracÃn-Ferrer, Mariano
Faculty of Medicine. University of Murcia, Spain.
Cárceles-Moreno, Francisco
Faculty of Medicine. University of Murcia, Spain.
Hernández-Gómez, Rubén
Faculty of Medicine. University of Murcia, Spain.
Hernández-Kakauridze, Sergio
Faculty of Medicine. University of Murcia, Spain.
Hernández-Sabater, Laura
Faculty of Medicine. University of Murcia, Spain.
Jiménez-Zafra, Ignacio
Faculty of Medicine. University of Murcia, Spain.
López-Alacid, Alberto
Faculty of Medicine. University of Murcia, Spain.
Moreno-Salmerón, Carmen
Faculty of Medicine. University of Murcia, Spain.
Pérez-Ramos, Miguel
Pathology Department, Morales Meseguer University Hospital, Murcia, Spain.
Nieto-Olivares, Andrés
Sánchez-Campoy, Nicolás
National Institute of Statistics, Lerida, Spain.
MartÃnez González-Moro, Ignacio
Faculty of Physiotherapy, University of Murcia, Spain.
Poblet, Enrique
Pathology Department, Reina Sofia University Hospital, Murcia, Spain
Digital Pathology; Ergonomics; Input Device; Fitts test; NASA-TLX; Voice recognition
Background
Digital Pathology represents a technological innovation that introduces changes in the traditional tasks of pathologists. In this regard, an important issue that has not been enough emphasized is the image handling from an ergonomic point of view to avoid work-related musculoskeletal disorders (MSD). The aim of this study was to investigate a proper input device for digital pathology.
Material & Methods
Research was conducted in two phases: (1). A comparative study to find out an optimal external controller. Eight medical students analyzed 11 input devices: keyboard (Hewlett Packard, HP), conventional mouse (HP), vertical mouse (CLS), touchpad (Logitech), 3 trackballs (Logitech, Kensington Expert and Ulove), Rollermouse (Contour), Ergopointer (Märzhäuser Sensotech), gamepad (Logitech) and a touchless device (Leap Motion Controller), using them with the Image Viewer software (Ventana). The web-based Fitts´ law test (UC Berkeley) was used to objectify the accuracy of each used device, randomly. 12 items were included in the questionnaire: comfort, technical aspects (cursor movement and objective achievement), prospects, overall satisfaction, prior experience, and others. (2). Evaluation by two experienced pathologists of the best rated input device on the previous experiment and its comparison with a voice recognition system (Invox Medical Dictation, Vocali) using a headset microphone (Plantronics). Perceived workload was scored using the NASA Task Load Index on 28 whole slide images visualized on the Digital Image Hub (Leica) platform with a 4 MegaPixel display (Barco). Data were processed with SPSS 21.0.
Results
Correlation between technical aspects of the evaluated devices and accuracy (Fitts´ law test), and comfort with overall satisfaction, was demonstrated (p<0.05). Comparative analysis of the 11 input devices concluded that vertical mouse was the best rated input device. However, on the second phase of the study, we find a slightly higher perceived workload using this device than using the voice recognition system, which was the best controller in digital pathology from an ergonomic point of view in this study.
Conclusions
We describe a methodology that can study and compare input devices for future workstations in digital pathology. Pathologists should be involved in this process trying to find ergonomic devices that prevent MSD. Voice recognition can function as a good handsfree device for digital pathology and could be considered in physical disability situations. Further studies using electromyography, accelerometry and 3D reconstruction analysis could provide additional ergonomic information.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/232
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/288
2022-07-15T07:32:42Z
dpath:RES
"220714 2022 eng "
2364-4893
dc
The diagnostic significance of reticulin stain in biopsy of adrenocortical carcinoma
Wu, Suhua
Tan, Wanlin
Yang, Ping
Zhang, Yijun
Huang, Mayan
Cao, Yun
Sun-Yat-sen university cancer center
Aims
To investigate the diagnostic significance of reticulin stain in biopsy of adrenocortical carcinoma.
Methods and results
21 cases of adrenal mass biopsy specimens collected at Sun Yat-sen University Cancer Center from November 2008 to July 2021 which included 19 cases of adrenal cortical carcinoma (ACC) and 2 cases of normal adrenal cortical were evaluated for their histologic,immunohistochemical(IHC)and reticulin stain features, and relevant literature was reviewed. The nuclei of ACC cancer cells were deeply stained, varying in size. Varying degrees of nuclear atypia, mitotic figures, focal necrosis and tumor giant cells were visible in ACC. Most of the cytoplasm was eosinophilic, some of the cytoplasm was transparent and the ACC cancer cells were nested, cord-like or diffuse distribution. In contrast, 2 cases of normal adrenal cortex puncture tissues showed that the cytoplasm of adrenal cortex cells was partially transparent, partly eosinophilic, with small nuclei and no atypia. Among ACC patients, 4 cases (4/19) were positive for CK. 6 cases (6/19) were positive for Vimentin. 8 cases (8/19) were positive for Inhibin-a, and 7 cases (7/19) were Melan-A positive. 7 patients (7/19) were positive for SF-1. 11 patients (11/19) were Syn positive and 4 patients (4/19) were CD56 positive. The Ki-67 index of the patients ranged from 2% to 90%. The reticulin stain of 2 cases of normal adrenal cortex showed that the reticular fibers were arranged regularly and completely wrapped the adrenal cortex cell. In the reticulin stain, a complete reticular fiber appeared, and the thickness of the fiber was moderate and uniform. In 19 cases of ACC, the reticular fiber was incomplete and damaged (19/19), mainly manifested as discontinuity, breakage, disorder, sparseness or disappearance.
Conclusion
Reticulin stain was an effective method for accurate diagnosis of adrenal cortical carcinoma.
DiagnomX GmbH
2022-03-31 16:45:51
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/288
Diagnostic Pathology; Vol 7 No 1 (2022): Vol 7 No 1
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/208
2019-08-22T16:03:15Z
dpath:RES
"160829 2016 eng "
2364-4893
dc
Cy-TEST - A new platform for training and testing in cytopathology
Lianas, Luca
CRS4 - CENTER FOR ADVANCED STUDIES, RESEARCH AND DEVELOPMENT IN SARDINIA
Piras, Marco Enrico
CRS4 - CENTER FOR ADVANCED STUDIES, RESEARCH AND DEVELOPMENT IN SARDINIA
Musu, Elodia
CRS4 - CENTER FOR ADVANCED STUDIES, RESEARCH AND DEVELOPMENT IN SARDINIA
Podda, Simona
CRS4 - CENTER FOR ADVANCED STUDIES, RESEARCH AND DEVELOPMENT IN SARDINIA
Frexia, Francesca
CRS4 - CENTER FOR ADVANCED STUDIES, RESEARCH AND DEVELOPMENT IN SARDINIA
Ovcin, Emanuela
COREP
Bussolati, Giovanni
COREP
Zanetti, Gianluigi
CRS4 - CENTER FOR ADVANCED STUDIES, RESEARCH AND DEVELOPMENT IN SARDINIA
elearning; telepathology; cytopathology; virtual microscopy
Introduction/ Background: Clinical training at the European level requires flexible ways to provide education across borders with the goal of a unified way to teach and assess quality. The Cy-TEST project focuses on Cytological Training at European Standard through Telepathology. The project (2014-1-IT01-KA202-002607) has been approved and funded in 2014 by EU within the ERASMUS+ Program. The project consortium is composed of 4 leading university Institutions (COREP and University of Turin, University of Padua, Imperial College of London, IPATIMUP/University of Porto and University of Graz) with technological development and support provided by CRS4. In addition, it benefits from the collaboration of International Organizations (EFCS, Eurocytology, OME) and is open to contributions from additional groups and Societies.
Aims: Our aim was the establishment of a platform for the sharing of digital pathology images and of an auxiliary system that will use the latter platform for the distribution of cytologist training courses with an integrated virtual microscopy capability.
Methods: The Cy-TEST platform is based on the integration between Moodle, an e-learning platform designed to create personalized learning environments, and OME OMERO, a well-known open source software for visualization, management and analysis of biological microscope images. The former is used to provide access to a database of questions produced by specialized trainers and the latter provides access to digital pathology images and related metadata. We chose to base our infrastructure upon Moodle because it is one of the top leading platform for online education with a large community of users across both academic and enterprise level, highly customizable and modular. OMERO was chosen because of its compatibility with a large number of image formats for digital pathology images, its handling of image metadata (i.e., TAGs and Regions of Interest) and its easily extensible web platform.
Results: The web platform can be used with a wide range of devices, it is compatible with most of the image formats produced by digital slides scanners and it can scale to a wide student body. Teachers can create courses, populate the Question Bank and aggregate questions in quizzes, while students can take classes and tests. When creating questions, teachers can choose images previously loaded and annotated. We provide two new types of questions: multiple choice, focused on an image and its ROIs, and interactive, where students identify areas on the image by markers that will be automatically compared to instructor’s specified ROIs. The currently deployed system holds already a set of several hundreds of images classified by categories (e.g., tissue type and diseases) with associated ROIs identified by pathologists. The Cy-TEST platform provides a full technological solution for a more homogeneous training and testing of cytotechnicians and cytopathologists with uniform quality level assurance mechanism. The system could be easily extended to support the teaching of histopathological diagnosis. Moreover, the Cy-TEST platform paves the way to an e-QUATE test, thus providing an efficient and economical way to replicate the test at European scale (see Branca et al., 2000). The sustainability of the platform and the supported educational material (images, questions and evaluation algorithms) will be guaranteed by its integration in EFCS activities. We expect to distribute the Cy-TEST System for validation by October 2016, for further information contact infocytest@corep.it.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/208
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/258
2019-08-22T15:02:31Z
dpath:RES
"180123 2018 eng "
2364-4893
dc
Protective Effect of Anar-5 Herbal Treatment on Experimental Chronic Atrophic Gastritis in Wistar Rats
Dungubat, Erdenetsogt
National University of Medical Sciences (MNUMS)
Dashzeveg, Uranzaya
Institute of Traditional Medicine and Technology of Mongolia
Buyantogtokh, Dejidmaa
Institute of Traditional Medicine and Technology of Mongolia
Chimedtseren, Chimedragchaa
Institute of Traditional Medicine and Technology of Mongolia
Enkhba, Bayarmaa
Purevjav, Batkhuyag
Mongolian National University of Medical Science
Background: Chronic gastritis is a slowly progressive disease. It includes atrophy of gastric mucosa, impairment of epithelial regeneration, formation of lymphoid tissue/germinal center, loss of gastric secretion and movement. The Mongolian traditional medicine used Anar-5 recipes for the treatment of stomachache, emesis, and improvement of gastricdigestion. Based on these observations, we implemented a rat model of Anar-5 treatment in artificial chronic gastritis in order to elucidate its potential protective mechanisms scientifically.
Methods and material: We established an experimental rat model of chronic gastritis by use of ammonia water. We divided the rat cohorts in an Anar-5–treated test group, an untreated cohort, and a control group. The untreated group was fed with 0.1% ammonia water and the treated group with both 0.1% ammonia water and administered Anar-5 100 mg/kg/day for 6 weeks. Gastric lesions were evaluated microscopically. The Prostaglandin E2 levels, cyclooxygenase COX-2 expression and the cellular proliferation marker Ki67 were in addition assessed.
Results: The Anar-5 cohort displayed with an increased thickness of the antrum mucosa, number (р˂0.05) and regeneration zones of gastric mucous epithelial cells when compared to the results of the untreated cohort (693.1±63.8 μm versus 429.6±43.5 μm). The untreated cohort displayed with decreased PGE2 levels (14.8±0.62 ng/dl) when compared to those of the control group and Anar-5 cohort (19.5±1.22 ng/dl and 8.7+0.32 g/dl protein, respectively). The Ki67-associated proliferation rate of the antrum mucosa was enhanced and measured 19.75% in the untreated cohort in comparison to a proliferation rate of 6.58% in the Anar-5 cohort.
Conclusion: The data of our rat experiment indicate that a contemporary application of Anar-5 herbs acts as a gastric mucosal protective agent. In addition it induces an overexpression of COX-2 and maintenance of the PGE2 lev
DiagnomX GmbH
2018-01-23 00:00:00
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/258
Diagnostic Pathology; Vol 4 No 1 (2018): 2018
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/93
2019-08-22T16:14:22Z
dpath:RES
"160117 2016 eng "
2364-4893
dc
The role of determining the nucleolar organizers in assessing the evolution of neoplasms
Fatu, Ana Maria
"Gr. T. Popa" University of Medicine and Pharmacy Iasi, Romania http://orcid.org/0000-0001-9271-3996
Fatu, Constantin
Vascu, Bogdan
Moscu, Mihaela
Endometrial Hyperplasia; Endometrial Adenocarcinoma; AgNOR; Mitotic count
Background: Nucleolar organizer regions are parts of chromosomes that code ribosomal RNA and correlate to cellular proliferation. They have been identified by means of an argyrophilic technique that reveals NORs as black dots in the nuclei. The method has been recently applied in some malignancies, as lymphoma or melanoma. Only few investigations on hormonal-dependent tumours have been published. Our aim was to investigate on the total number of AgNORs and cell type of endometrial tumors.
Material and Methods: We studied 21 cases of formalin fixed paraffin embedded endometrial tumors including hyperplasia. The number of AgNORs was counted in both epithelial and stromal components. A total of 13 cases were benign and 8 malignant lesions.
Results: The total number of AgNORs was found to correlate with mitotic counts both in benign lesions and malignancies. The mean number of AgNORs increased from 2.79 in simple endometrial hyperplasia to 10.0 in adenocarcinoma.
Conclusions: Our data indicate that the AgNORs visualization can assist to differentiate between different malignancy grades of endometrial proliferations, especially between complex endometrial hyperplasia and atypical hyperplasia as well as endometrial adenocarcinomas.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/93
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/248
2019-08-22T15:52:52Z
dpath:RES
"170728 2017 eng "
2364-4893
dc
Cognitive Algorithms and digitized Tissue – based Diagnosis
Görtler, Jürgen
IBM Global Markets, Systems, Frankfurt, Germany
Kayser, Klaus
Charite, Berlin, Germany
Borkenfeld, Stephan
IAT, Heidelberg, Germany
Carvalho, Rita
Central Lisbon Hospital Center, Department of Pathology, Lisbon, Portugal
Kayser, Gian
Institute of Surgical Pathology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Aims: To analyze the nature and impact of cognitive algorithms and programming on digitized tissue – based diagnosis.
Definitions: Digitized tissue – based diagnosis includes all computerized tissue investigations that contribute to the most appropriate description and forecast of the actual patient’s disease [1]. Cognitive algorithms are programs that encompass machine learning, reasoning, and human – computer interaction [2].
Theoretical considerations: Digitized blood data, objective clinical findings, microscopic, gross, radiological images and gene alterations are analyzed by specialized image analysis methods, and transferred in numbers and vectors. These are analyzed by statistical procedures. They include higher order statistics such as multivariate analysis, neural networks and ‘black box’ strategies, for example ‘deep learning’ or ‘Watson’ approaches. These algorithms can be applied at different cognitive ‘levels’, to reach a digital decision for different procedures which should assist the patient’s health condition. These levels can be grouped in self learning, self promoting, self targeting, and self exploring algorithms. Each of them requires a memory and neighbourhood condition. Self targeting and exploring algorithms are circumscribed mechanisms with singularities and repair procedures. They develop self recognition.
Consecutives: Medical doctors including pathologists are commonly not trained to understand the basic principles and workflow of applied or potential future procedures. At present, basic medical data only serve for simple cognitive algorithms. Most of the investigations focus on ‘deep learning’ procedures. The applied learning and decision algorithms might be modified and themselves be used for ‘next order cognitive algorithms’. Such systems will develop their own strategies, and become independent from potential human interactions. The basic strategy of such IT systems is described herein.
Perspectives: Medical doctors including pathologists should be aware about the abilities to enhance their work by supporting tools. In some case the users may not be able to fully understand these tools. Furthermore, these tools will probably become self learning, and, therefore, seem to propose the daily workflow probably without any medical control or even interaction.
DiagnomX GmbH
2017-02-09 12:31:05
application/pdf
application/xml
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/248
Diagnostic Pathology; Vol 3 No 1 (2017): 2017
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/11
2018-06-19T09:07:29Z
dpath:RES
"150410 2015 eng "
2364-4893
dc
Cytology ABCDE: A Practical ABCDE Algorithm for Cytology Diagnosis
Zioga, Christina
Theagenio Anticancer Hospital of Thessaloniki, Greece http://orcid.org/0000-0003-1160-1410
Destouni, Chariklia
Theagenio Anticancer Hospital of Thessaloniki, Greece
Pathology; diagnosis; cytology diagnosis; cytology algorithm; diagnosis report
Aims
An approach to the process of undertaking cytopathology diagnosis for medical students and those who operate with cytology specimens is presented.
Material and Methods
This simple mnemonic (ABCDE) can be used as a memory aid determining the order in which cells or tissue fragments should be evaluated. When receiving a slide for diagnosis and prior to examining it under the microscope we need to make sure that it is correctly labelled and prepared (Correct) and we also need to know or gather all available information concerning the patient (A, Available Information). Once under the microscope, we check the type of cells and the adequacy of specimen (B, Body & Being Adequate). Next, by taking into consideration the cellular morphology and potentially by performing ancillary studies we proceed to answer if the cells are neoplastic or not (C, Cancer). We then either form a differential diagnosis list or we end up with our final diagnosis (D, Differential diagnosis or Diagnosis), which is followed by the writing of the report (E, Exhibit).
Results
These sequential steps (Correct ABCDE) followed as an ad hoc procedure by most pathologists, are important in order to achieve a complete and clear diagnosis and report, which is intended to support optimal clinical practice.
Conclusions
This ABCDE concept is a generic standard approach which is not limited to specific specimens and can help improve both cytopathology diagnoses and the quality of the final cytopathology reports.
DiagnomX GmbH
2015-01-08 17:32:29
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/11
Diagnostic Pathology; 2015
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/235
2019-08-22T16:04:25Z
dpath:RES
"161217 2016 eng "
2364-4893
dc
Presence of PCR artifacts in Sanger sequencing in Formalin-fixed paraffin-embedded (FFPE) tissue – experience in a collective of 990 advanced NSCLC
Kayser, Claudia
Albert-Ludwigs-University Freiburg
Csanádi, Ãgnes
Bittermann, Nicola
Guenter, Jutta
Rawluk, Justyna
Fisch, Paul
Werner, Martin
Kayser, Gian
Lung cancer, molecular analysis, Sanger sequencing, fixation artifacts, PCR artifacts, EGFR
Background: Despite the rapid development of new molecular techniques such as Next Generation Sequencing (NGS), Sanger sequencing has been thus far the gold standard for mutation analysis. It is constantly used for daily routine diagnostics because it represents a quick and comprehensive available method for mutation analyses. Although Sanger sequencing is a good validated method, PCR artifacts may occur in formalin fixed paraffin embedded (FFPE) material. This constitutes a serious source of error.
Aims: To assess the prevalence of typical and atypical EGFR mutations in exon 19 and 21 in a collective of 990 advanced non-small cell lung cancer (NSCLC) patients, focusing especially on methodological issues and challenges concerning mutation analysis, particularly PCR artifacts.
Material and Methods: We examined 990 NSCLC (FFPE material) by Sanger sequencing for exon 19 and 21 of the EGFR gene. Four cases dropped out because of insufficient DNA quality (n =986). Results: Beside 101 typical exon 19 and 21 mutations (99 cases, two double mutations) we found 45 additional cases with distinct peaks at atypical positions in exon 19 and 21 in our first analysis. This would have implied a mutation rate of 14.6 %. Only six of these putative atypical mutations (all exon 21 and none of the exon 19 mutations) could be validated by repeated mutation analysis. All other peaks were not reproducible, therefore considered as PCR artifacts and consequently as wild type. Altogether we found 105 cases (107 mutations, 10.6 % of cases) with typical/atypical mutations in exon 19 and 21 of the EGFR gene.
Conclusion: In our opinion it is in general important to detect and report all mutations even at atypical sites to discover their possible clinical relevance. However, one must always be aware of the possibility, reasons and prevention of PCR artifacts in FFPE tissue. Therefore, prior to reporting mutations at uncommon sites these must be validated by repeated analyses.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/235
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/115
2018-06-19T09:02:14Z
dpath:RES
"160912 2016 eng "
2364-4893
dc
Efficient pathology case distribution leveraging workflow and domain modeling, and flexible definition of policies
Bucur, Anca
Philips Research
van Leeuwen, Jasper
Philips Research
Vdovjak, Richard
Philips Healthcare
Case distribution; digital pathology; workflow modeling and optimization; automatic dispatching; workflow engine; rules engine
Background
The value of digital pathology and its potential to improve the current pathology practice are increasingly recognized, with a growing number of examples of successful implementation in a variety of use cases. While current widely-spread uses relate to research, consultation, second opinion and education, success stories are emerging demonstrating outcome and cost benefits of leveraging digital pathology for standard diagnosis as well. In all these cases optimization of pathology workflows, standardization and seamless integration in the environment are emphasized as prerequisites to reaching the desired improvements.
Aims
We develop workflow-driven applications to enable clinical users to efficiently and effectively leverage deployed digital pathology solutions for faster diagnosis and better patient outcomes. The work addresses information integration requirements, and aims to identify and propose solutions for performance bottlenecks in existing processes. A process with potential for improvement is the case distribution to pathologists for diagnosis.
Materials and Methods
We propose an approach to workflow modeling and implementation that is open and flexible, and leverages existing standards (BPMN2.0) developed in the context of business process modeling and widely adopted in other domains. This enables efficient implementation and give us access to an existing platform (KIE) that delivers a workflow-engine (jBPM), a rule-engine (Drools), and a constraint satisfaction solver (OptaPlanner). By externalizing the definitions and implementations of tasks within the workflows, we build workflows that are adaptive to the environment and that can incorporate decision models and applications of the desired complexity. We selected case distribution for diagnosis as the first process to optimize and built an application that can be efficiently customized to the needs of each lab with respect to dispatching rules, operational domain model, optimization goals and visual elements.
Results
We implemented a case distribution application that can be deployed within an integrated workflow implementation to optimize the distribution of cases to pathologists for diagnosis. To automatically assign cases to pathologists according to defined policies, the optimization component applies the defined policy model (scoring rules within the domain model). The schedules are generated according to the desired optimization goals, e.g. to improve throughput or turnaround. This application seamlessly connects with relevant systems in the environment, the LIMS and the IMS, in a loosely-coupled standard way through the integration engine to retrieve all needed data about the cases to be visualized and used in the dispatching decisions, and to provide the case assignation information to the IMS.
Conclusions
The optimization of the case distribution to pathologists for diagnosis has been identified in the literature as an important area when aiming at workflow improvements and automation of the processes in the pathology labs. A common theme emphasized by previous research identifying user needs and requirements for efficient digital pathology implementation is the use of standards to support adoption and the seamless integration with all relevant systems in the environment. Within a standards-based workflow-driven approach, we implement a case distribution application that optimizes the case assignation for diagnosis by modeling the local workflows and the requirements of each deployment site. The optimization component applies the local policy models (i.e. business rules, domain models with roles and characteristics, and optimization goals) to propose the most suitable solution for distributing the incoming case load among the available pathologists for diagnosis.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/115
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/275
2019-07-05T16:06:17Z
dpath:RES
"190704 2019 eng "
2364-4893
dc
Etiology and Pathogenesis of Sudden Cardiac Death
Guski, Hans
Institute of Pathology (Virchow Institute), Faculty of Medicine (Charité), University of Berlin
Kogan, Evgenya A.
Chair of Pathological Anatomy, First Moscow State University (Sechenov University)
Shvalev, Vadim N.
Cardiological Research Center Moscow of the Academy of Medical Science
Background and definition: This article contributes to the current state of knowledge in etiology and pathogenesis of sudden cardiac death (SCD). SCD is a well - defined disease entity which recently approved international guidelines address (cardiac death within 1 hour).
Etiology: The condition of coronary arteries contributes to common causes of SCD. Stenotic coronary artery sclerosis (80%) has been reported in most cases. In non-coronary causes (15%), cardiomyopathies (CMP) are frequently found, and alcoholic CMP dominates the CMP cohort. Genetically related causes are comparatively rare (5%).
Pathogenesis: In pathogenesis, only the consecutives of coronary ischemia have been extensively studied, in contrast to non-coronary causes. Herein, only some (mostly infectious) forms of myocarditis have been investigated in detail. The pathogenesis of different causes of SCD is less well studied. These include pathologic changes of adrenergic and cholinergic heart nerves, of intra- and extra-cardiac ganglia and of the conduction system. Morphological changes that clearly explain SCD are still difficult to reproducibly detect in clinical-pathologic and forensic autopsy diagnosis because these lesions might morphologically at first manifest after 1 hour or even later. This statement holds particularly true for detecting early ischemic heart muscle cell deaths being the most common cause of SCD
Conclusions: The reported methods and special staining have proven to be less suitable for routine diagnostics. Attempts are now undergoing to solve the problem by the use of specific antibodies. They provide evidence of immunoreactivity of ischemic damaged cardiomyocytes which can be detected even after prolonged postmortem lay times.
DiagnomX GmbH
2019-07-04 12:04:10
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/275
Diagnostic Pathology; Vol 5 No 1 (2019): Vol. 5 No. 1 2019
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/104
2019-08-22T16:09:26Z
dpath:RES
"160420 2016 eng "
2364-4893
dc
Novel anti-human Axl monoclonal antibodies for improved patient biomarker studies
Ahmed, Lavina
BerGenBio AS and Center for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Norway
Kiprijanov, Sergej M
BerGenBio AS
nalwoga, Hawa
Center for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Norway
Wnuk-Lipinska, Katarzyna
BerGenBio AS
Haugen, Hallvard
BerGenBio AS
Lorens, James B
BerGenBio AS and
University of Bergen, Norway
Akslen, Lars A
Centre for Cancer Biomarkers, University of Bergen, Norway and
Department of Pathology, Haukeland University Hospital, Bergen, Norway
Micklem, David Robert
BerGenBio AS http://orcid.org/0000-0003-2756-2591
Monoclonal antibodies; cancer; EMT; diagnostic biomarkers; Axl; ELISA; IHC; Western blot
Background: Axl receptor tyrosine kinase has been associated with poor clinical outcome in a wide variety of malignancies including breast, lung, prostate, pancreatic, brain and myeloid cancers. Axl is up-regulated during tumour epithelial-to-mesenchymal transition (EMT) and is associated with metastasis, immune evasion and drug resistance.
Methods: The aim of this study was to develop improved assays for detection of Axl protein in patient samples. We developed a panel of mouse monoclonal antibodies directed against the extracellular domain of human Axl, from mice immunized with a recombinant antigen comprising the extracellular domains of human Axl fused to human IgG1 Fc domain. Anti-Axl monoclonal antibodies (MAbs) were assessed for sensitivity, specificity and utility using surface plasmon resonance (SPR) analysis, sandwich enzyme-linked immunosorbent assay (ELISA), Western blot analysis and immunohistochemistry (IHC) staining.
Results: One of the anti-human Axl MAb,1H12, performed particularly well, and SPR analysis confirmed both high affinity (50 pM) and high selectivity for Axl versus other Axl-family receptors. In IHC applications on selected human carcinomas and cancer cell line pellets, MAb 1H12 showed improved sensitivity and reduced background staining compared to other members of the MAb panel. A second MAb 5F11 showed very high affinity (5.8 pM) at a non-overlapping epitope and was selected as a partner for 1H12 in sandwich ELISA, producing a highly sensitive and specific assay.
Conclusion: MAbs 1H12 and 5F11 represent new anti-human Axl monoclonal antibodies for improved patient biomarker studies.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/104
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/249
2019-08-22T15:52:02Z
dpath:RES
"170807 2017 eng "
2364-4893
dc
Evaluation of a confocal WSI scanner for FISH slide imaging and image analysis
Fu, Xiujun
Memorial Sloan Kettering Cancer Center
Lennerz, Jochen K.
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Onozato, Maristela
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Iafrate, Anthony
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Yagi, Yukako
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Background: Technological advances contribute to the maturation of digital pathology in clinical and research applications. However, there are only few reports on fluorescence scanning especially on confocal fluorescence imaging technology in digital pathology, which has superior depth resolution compared to wide-field fluorescence imaging. Here, we explored the features of a confocal WSI scanner for typical diagnostic and research imaging applications of fluorescence in situ hybridization (FISH) assay.
Methods: Multi-layer stacking (Z-stack) which stores all image information from each layer, and extended focus which stores the optimal image information from all scanned layers, featured in the Pannoramic Confocal scanner (3DHISTECH Ltd., Budapest, Hungary) were employed in digitizing 14 FISH slides (ALK, EGFR, and multi-gene). The slides were scanned with a 40× water immersion objective producing a final image with pixel resolution of 0.1625 µm/pixel. Z-stack and extended focus were used for N=6, 13, and 26 multiple layers scanning at 1, 0.4, and 0.2 µm depth intervals respectively. Single-layer scanning was also done for comparison. Scanning time and resultant file size were recorded. The CaseViewer from 3DHISTECH was used to visualize images and export the annotated regions, and the exported images were further analyzed in Imaris (Bitplane, Zurich, Switzerland) for 3-dimensional reconstruction, nuclear segmentation, and the quantification and co-localization analysis of dots inside nuclei. Quantification data from Imaris were imported into Excel for statistic analysis.
Results: Confocal fluorescence scanning of FISH slides enabled sharper image than wide-field scanning, although it required longer scanning time and larger file storage. More intra-nuclear dots were quantified from multi-layer Z-stack images than single-layer images, and the Z-stack increased scanning time and image file size. Furthermore, there were a reduced in the number of dots and an increased in the number of co-localized dots in extended-focus images compared to Z-stack. Dots in multiple channels were quantified and analyzed automatically, which supports clinical diagnosis of gene amplification, deletion, and translocation. Three-dimensional reconstruction of Z-stack produced precise measurement of spatial distance, which supports molecular research.
Conclusion: Confocal provides sharper image than wide-field for FISH slide scanning. Extended focus reduces file size and storage, but could cause inaccurate analysis due to misinterpretation of overlapping information. Z-stack scanning provides high volume image information for spatial analysis. We foresee confocal multi-layer scanning as a digital pathology application tool for FISH imaging in both clinical and research in future.
DiagnomX GmbH
2017-02-09 12:31:05
application/pdf
application/xml
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/249
Diagnostic Pathology; Vol 3 No 1 (2017): 2017
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/13
2018-06-19T09:07:29Z
dpath:RES
"150427 2015 eng "
2364-4893
dc
EGFR and KRAS mutation coexistence in lung adenocarcinomas
Sousa, Vitor Manuel Leitão de
1 Institute of Anatomical and Molecular Pathology, Faculty of Medicine of the University of Coimbra, Coimbra, Portugal
2 CIMAGO – Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
3 Centre of Pulmonology, Faculty of Medicine of the University of Coimbra, Portugal
4 Service of Anatomical Pathology, University Hospital of Coimbra, Coimbra, Portugal
Silva, Maria Reis
1 Institute of Anatomical and Molecular Pathology, Faculty of Medicine of the University of Coimbra, Coimbra, Portugal
2 CIMAGO – Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
3 Centre of Pulmonology, Faculty of Medicine of the University of Coimbra, Portugal
Alarcão, Ana Maria
1 Institute of Anatomical and Molecular Pathology, Faculty of Medicine of the University of Coimbra, Coimbra, Portugal
2 CIMAGO – Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
3 Centre of Pulmonology, Faculty of Medicine of the University of Coimbra, Portugal
d’Aguiar, Maria João
1 Institute of Anatomical and Molecular Pathology, Faculty of Medicine of the University of Coimbra, Coimbra, Portugal
Ferreira, Teresa
1 Institute of Anatomical and Molecular Pathology, Faculty of Medicine of the University of Coimbra, Coimbra, Portugal
Carvalho, Lina
1 Institute of Anatomical and Molecular Pathology, Faculty of Medicine of the University of Coimbra, Coimbra, Portugal
2 CIMAGO – Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
3 Centre of Pulmonology, Faculty of Medicine of the University of Coimbra, Portugal
4 Service of Anatomical Pathology, University Hospital of Coimbra, Coimbra, Portugal
KRAS; EGFR; Bronchial-pulmonary carcinomas.
Lung cancer is one of the most common causes of cancer deaths. The development of EGFR targeted therapies, including monoclonal antibodies and tyrosine kinase inhibitors have generated an interest in the molecular characterization of these tumours. KRAS mutations are associated with resistance to EGFR TKIs. EGFR and KRAS mutations have been considered as mutually exclusive.
This paper presents three bronchial-pulmonary carcinomas, two adenocarcinomas and one pleomorphic sarcomatoid carcinoma, harboring EGFR and KRAS mutations.
Case 1 corresponded to an adenocarcinoma with EGFR exon 21 mutation (L858R) and KRAS codon 12 point mutation (G12V); case 2, a mucinous adenocarcinoma expressed coexistence of EGFR exon 21 mutation (L858R) and KRAS codon 12 point mutation (G12V); and case 3 a sarcomatoid carcinoma with EGFR exon 19 deletion – del 9bp and KRAS codon 12 point mutation (G12C - cysteine).
Based on our experience and on the literature, we conclude that EGFR and KRAS mutations can indeed coexist in the same bronchial-pulmonary carcinoma, either in the same histological type or in different patterns. The biological implications of this coexistence are still poorly understood mainly because these cases are not frequent or currently searched. It is therefore necessary to study larger series of cases with the two mutations to better understand the biological, clinical and therapeutic implications.
DiagnomX GmbH
2015-01-08 17:32:29
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/13
Diagnostic Pathology; 2015
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/238
2019-08-22T16:00:09Z
dpath:RES
"170209 2017 eng "
2364-4893
dc
Morphometric study of facial wrinkles and aesthetic skin as dermaroller treatment combined with platelet rich plasma (PRP)
Oyunsaikhan, Surmaajav
Department of Oral and Maxillofacial Surgery, School of Dentistry, Mongolian National University of Medical Sciences
Amarsaikhan, Bazar
Department of Prosthodontics, School of Dentistry, Mongolian National University of Medical Sciences
Batbayar, Badral
Department of Oral and Maxillofacial Surgery, School of Dentistry, Mongolian National University of Medical Sciences
Dungubat, Erdenetsogt
National University of Medical Sciences (MNUMS)
dermaroller, platlet rich plasma, PRP, wrinkle, skin aging
Background: Facial wrinkles are a multifactorial, complex process that negatively affects individuals’ appearance, consequently their quality of life. The treatment for these wrinkles varies with the degree of severity. This prospective study aimed to evaluate the clinical effect of pure dermaroller and dermaroller combined with platelet rich plasma therapy (PRP dermaroller), to treat facial wrinkles, and to quantitatively evaluate histological changes of the skin that occur in the two different cohorts.
Methods and materials: Twenty healthy women aged 43-48 years with scores ranging between 2 and 4 on the baseline facial fine wrinkle grading scale were enrolled in the this clinical study. Nineteen of the patients were treated with a pure dermaroller on the one half of face, and with a dermaroller that included a platelet rich plasma on the other half of the face. Three treatments, each in a 4 weeks interval were performed. Standard photographs and skin biopsies were obtained from the treatment area at baseline and 8 weeks after the final session. Comparisons of the treatments were analyzed using clinical and histological findings.
Results: The degree of baseline facial fine wrinkle grading scale after treatment revealed statistically significant effects of the PRP dermaroller treatment side compared to the side of pure dermaroller treatment. At 8 weeks after the final session, the wrinkling grade on the PRP dermaroller side and the pure dermaroller side showed significant differences (p<0.05). Microscopic evaluation of haematoxylin eosin and Masson’s trichrome stained sections revealed significant differences in dermal fibers, epidermal thickness, papillas and skin glands.
Conclusion: Significant changes were noted between treatments of facial wrinkles with pure dermaroller and PRP dermaroller. Dermaroller combined with platelet rich plasma is a promising novel method of facial rejuvenation.
DiagnomX GmbH
2017-02-09 12:31:05
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/238
Diagnostic Pathology; Vol 3 No 1 (2017): 2017
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/114
2018-06-19T10:05:55Z
dpath:RES
"160914 2016 eng "
2364-4893
dc
The effects of digital workflow control for the performance of routine pathology
Haroske, Gunter
Hospital Friedrichstadt - Dresden
Moerz, Michael
Hospital Friedrichstadt - Dresden
digital pathology; pathology workflow; LIS; IHE profiles; HL7; DICOM; WSI; affectivity
Introduction/ Background
Although the scanning technology for microscopic slides has been known for more than 15 years, its practical use in daily routine is still on the very beginning. Fast and reliable scanners enabled their increasing use in teaching, but not yet in consultation and primary diagnostics. So far the scanning is not handled as a process in the pathology laboratory by most of the pathology systems, leading to an interrupted workflow with delays and additional expenses. The requirement pro les for slide scanners can only be formulated with respect to their workflow integration.
Aims
The effects of different degrees of workflow digitalization have been studied as to analyze the sources of possible benefits of digital pathology as well as to identify the bottlenecks and inconsist-encies in the workflow control in a routine pathology laboratory. The adherence to existing IHE Technical Frameworks has been evaluated, too.
Methods
Performance statistics of routine pathology were evaluated in different phases of digital workflow control over more than 10 years in a medium-sized institute of pathology. Three phases were de-fined: 1. Uncontrolled, but digitally supported workflow with digital dictation, digital macrophotography, digital microphotography at few pathology workstations, and a "classic" pathology software system 2. Digital workflow control including digital dictation and digital photography. 3. In a pilot study at the end of the evaluation period the additional benefits of slide scanning were estimated.
Results
In the period between 2005 and 2015 a decrease of turnaround-time of roughly 20% was seen. Alone the effects of a (sub)total digital workflow control contributed about half of that effect. The implementation of slide-scanning did not add further acceleration so far, but enabled some additional functionality for improving quantitative reporting. This was achieved without an explicit commitment of the pathology software to standards in workflow control and with still leaving a few laboratory processes out of the control. Milestones and key elements of workflow management are reported in detail.
Conclusion
All processes both in the laboratory and in the diagnostics have to be checked (and changed, if necessary) for being fit in a streamlined pathology workflow. The implementation of scanners into the routine diagnostics will enforce those essential developments leading to increased productivity and quality.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/114
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/273
2019-08-22T14:46:14Z
dpath:RES
"190710 2019 eng "
2364-4893
dc
Development of Standard Operating Procedure (SOP) of Micro-computed tomography (micro-CT) in Pathology
Teplov, Alexei
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Tabata, Kazuhiro
1. Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, 2. United States Department of Pathology, Nagasaki University Hospital. 1-7-1 Sakamoto, Nagasaki city, Nagasaki, 852-8501, Japan
Fu, Xiujun
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Uraoka, Naohiro
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States (2) Department of Pathology, Nagasaki University Hospital. 1-7-1 Sakamoto, Nagasaki city, Nagasaki, 852-8501, Japan
Roehrl, Michael H. A.
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Ntiamoah, Peter
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Humm, John L.
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Sirintrapun, Sahussapont J.
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Murray, Melissa P.
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Shia, Jinru
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Travis, William D.
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Brogi, Edi
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Hameed, Meera
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, United States
Yagi, Yukako
Memorial Sloan Kettering Cancer Center
Backgroundand goal: Micro-computed tomography (micro-CT) is an emerging technology in the biomedical field and enables us to analyze 3D structures non-destructively and observe these structures in various directions, thus enabling innovation in this area of pathology. However, application of micro-CT for medicine has just started and optimization per purpose has not yet been done. The purpose of this study is to 1) demonstrate the potential utility of micro-CT in pathology; 2) optimize micro-CT imaging technology and develop a standard operating protocol and; 3) investigate whether micro-CT incurs any radiation damage to pathological tissue samples.
Material and methods:The samples of fresh tissue, formalin fixed tissue and formalin fixed paraffin-embedded (FFPE) tissue blocks were scanned using a custom-built Nikon Metrology micro-CT system with a variety of parameters then evaluated with histology correlation in detail. Radiation damage to tissue samples was also evaluated. Through our study, we have established the scanning protocol and workflow for each type of sample.
Results:For fresh/fixed tissue, the house made polystyrene foam container was most ideal and the scanning time for fresh tissue was six minutes at as shortest, in which it is possible to detect neoplastic lesions in the tissue. In case of FFPE blocks, 10 -17 hours scanned images
DiagnomX GmbH
2019-07-04 12:04:10
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/273
Diagnostic Pathology; Vol 5 No 1 (2019): Vol. 5 No. 1 2019
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/106
2019-08-22T16:06:42Z
dpath:RES
"160421 2016 eng "
2364-4893
dc
How to analyze Structure and Function in Tissue – based Diagnosis?
Kayser, Klaus
Charite - Berlin
Borkenfeld, Stephan
Carvalho, Rita
Djenouni, Amina
Kayser, Gian
Digital pathology; structure, function; galectin-7; structural entropy; cellular heterogeneity
Background: Tissue – based diagnosis (morphological analysis of human tissue) judges, measures and interprets morphologic images which have been acquired from human tissue. It translates the findings into a diagnosis or description of biological functions. What are its principle algorithms and theoretical background?
Theory:Pathologists are used to distinguish between structure and function. Biological structures are ordered clusters of material (genes, nuclei, cells, organs, etc.), which remain constant during the period of detection and observation. They are commonly embedded or appear in circumscribed spaces. These spaces are clearly separated from their environment (background). Functions are forces that act on structures. They modify their appearance, create and delete structures and their spatial relationship. The recognition of both structures and functions is dependent upon the observation time: Material that remains unchanged within the observation period is called structure, its changes between a series of observations a function.
Derivatives: Biological structures and functions should be interpreted in relation to the observation time. Functions can be considered structural gradients of time or of observation periods.
Implementation: The analysis of conventional stained histological slides reflects to a short non changeable observation time, which in reality cannot be repeated at different times on the same tissue. Acquired digital images such as virtual slides (VS) offer the opportunity of simulating different observation times if object features are analyzed that reflect structural changes at different times. The measurement of immunohistochemal intensity levels performed on the same structure can be considered a time series of the binding or antigen – antibody process. The obtained frame of these measurements can be mapped on chemical significant descriptors such as Shannon’s and structural entropy, and their entropy flows.
Material and Methods: Histological glass slides displaying with kidneys of 39 chicken embryos were incubated with AP labelled galectin-3. In addition, 20 control cases were analyzed. One snapshot per case was digitalized and the staining intensity was measured in relation to a series of segmentation grey levels (0 – 255). The data were mapped on the principal measures Shannon’s and structural entropy as well as on the entropy flow derived from texture analysis.
Results: The mapped functions of entropies display with significant changes between the galectin-3 positive images and their negative control counterparts. The data indicate that the binding capacities of galectin-3 hold a significant function during the development of foetal chicken kidneys.
Conclusions: Laboratory techniques that simulate time-related series of measurements can be used to describe and interpret biological functions in living organisms at the cellular level.
DiagnomX GmbH
2016-01-17 11:46:24
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http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/106
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/251
2019-08-22T15:50:14Z
dpath:RES
"170820 2017 eng "
2364-4893
dc
The application of structural entropy in tissue based diagnosis
Kayser, Gian
Institute of Surgical Pathology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Görtler, Jürgen
IBM Global Markets, Systems, Frankfurt, Germany
Weis, Cleo Aron
Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
Borkenfeld, Stephan
IAT, Heidelberg, Germany
Kayser, Klaus
Charite - Berlin
Background: Entropy belongs to the few basic measurable entities in nature. It measures the distance of a closed or open ‘statistical’ system from its present stage to its final stage, and analyzes the probability distribution of the included elements, independently from their meaning. The development can be predicted by use of an ‘ideal transformation’, i.e. additive formula (for example Shannon’s entropy) or by mathematical derivatives such as the more generalized q – entropy, for example Tsallis entropy. Herein, the internal structures of the system are described which include so – called macro – systems. They are created by individual elements or basic micro – systems, and transformed into essentials of tissue – based diagnosis.
Entropy and neighborhood: The basic entropy approaches consider a spatially force – independent system, i.e., the calculation of the elements’ probability distribution does not take into account the formation of macro – systems, or the position of the individual elements within the system or between individual elements. The receiver of an informative signal cannot distinguish whether it has been generated in the center or at the boundary of the system. Only the signal’s probability within the information chain and the formation of the chain are informative. However, neighborhood plays an important role in development, maturation, degradation, and dissolution of biological systems. Most cells are generated by cellular division and neighboring cells are more similar in morphology and function than non-neighboring cells. This observation also holds true for ‘higher order’ biological systems such as animal colonies, forests, or even human societies. Thus, a potentially successful approach of estimating the development of a biological system should include neighborhood definitions and considerations.
Neighborhood conditioned (MST) entropy and entropy flow: Any definition of a neighborhood condition is based upon the distances between different elements, called objects. The distances can be weighted by additional object features, might be ‘directed’, or might include certain ‘shadow’ conditions (hidden behind another object). The most frequently used algorithm has been introduced by Voronoi in 1902. It can be successfully formulated in graph theory and derived approaches. In microscopic morphology, the construction of weighted minimum spanning trees (MST) is a convincing approach. Living biological systems are open and not closed. They exchange energy, information, and directives for future development with their environment. They have to stabilize their own entropy level against that of their environment. The mandatory entropy exchange or entropy flow from the individual element into its environment or vice versa reflects to the system’s stability and impact on its environment.
Tissue–based diagnosis and entropy: Tissue–based diagnosis includes all technical procedures to ascertain a ‘medical diagnosis’, such as microscopic, electron microscopic investigations, gene analysis, proteomics, syntactic structure analysis, liquid biopsies, etc. Herein, the transformation and applicability of the entropy approach are described and discussed.
DiagnomX GmbH
2017-02-09 12:31:05
application/pdf
application/xml
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/251
Diagnostic Pathology; Vol 3 No 1 (2017): 2017
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/14
2018-06-19T09:07:28Z
dpath:RES
"150526 2015 eng "
2364-4893
dc
Texture and object related image analysis in microscopic images
Kayser, Klaus
Charite - Berlin
Borkenfeld, Stephan
http://orcid.org/0000-0002-1476-8083
Djenouni, Amina
Pathology Institute, Batna (Algeria)
Kayser, Gian
Institute of Pathology, University, Freiburg, Germany
Tissue-based diagnosis; content image analysis; MST entropy; Immunohistochemistry; Glycohistochemistry; Segmentation
Background
Tissue based diagnosis or surgical diagnostic pathology undergoes significant changes and focuses on image content analysis in our days. Herein we describe and discuss new approaches of content image analysis and compare their applications, benefits and constraints.
Theory
Any useful microscopic image contains information that can be evaluated and transferred into a tissue-based diagnosis. A correctly derived diagnosis depends upon the image information and the pathologist’s knowledge, i.e. his ability to recognize and transfer the image content information into clinical application. Thus, image information is related to external “disease†information and “pure†image content information. Application of external image information requires a separation of objects from the background, or segmentation procedures. “Pure†image information is solely pixel based. It can be analyzed using different approaches, such as entropy measure, construction of image primitives and their spatial distribution, or image similarity operations. Our approach uses entropy calculations dependent upon all possible gray value thresholds in combination with syntactic analysis of pixel based image primitives.
Implementation
Virtual slides underwent the evaluation of regions of interest (ROI) as described previously. ROIs were interactively controlled and subject for application of developed image analysis procedures. The “classic method†of object recognition and syntactic structure analysis is applied too. Trials were performed on antie Her2_new stained, DAB visualized, and glycohistochemically stained, AP visualized slides. The images were measured at magnifications, which correspond to x20, and x40 objectives.
Results
The algorithm displayed only weak changes of the evaluated gray level based structural entropy (GL-MST)-entropy in the selected ROIs in contrast to the whole image. In addition, significant differences could be obtained when the measures were associated to the clinical impact (diagnosis, fetal developing stage).
Conclusions: Images textures and pixel primitives can serve for evaluating “pure†image content information. They do not require segmentation and additional external information for measurement. Interpretation of the measures, i.e. external information can be implemented at a later stage. The described algorithm is probably applicable for image analysis of different fields such as histology, forests, traffic, or can serve for objective image quality evaluation.
DiagnomX GmbH
2015-01-08 17:32:29
application/pdf
text/html
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/14
Diagnostic Pathology; 2015
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/241
2019-08-22T15:59:05Z
dpath:RES
"170319 2017 eng "
2364-4893
dc
Phosphohistone 3 (PHH3) and lactate dehydrogenase 5 (LDH5) are expressed in ductal carcinoma in situ of the breast: possible clinical implications
Sillem, Martin
Praxisklink am Rosengarten
Augustaanlage 7-11
68165 Mannheim
Baum, Sascha
Universitätsklinikum Schleswig-Holstein, Klinik für Frauenheilkunde und Geburtshilfe Campus Lübeck.
Ratzeburger Allee 160, 23538 Lübeck
Engist, Stefanie
Universitätsklinikum Freiburg, Department für Pathologie, Institut für Klinische Pathologie
Breisacher Str. 115A
79106 Freiburg
Kayser, Gian
Universitätsklinikum Freiburg, Department für Pathologie, Institut für Klinische Pathologie
Breisacher Str. 115A
79106 Freiburg
Werner, Martin
Universitätsklinikum Freiburg, Department für Pathologie, Institut für Klinische Pathologie
Breisacher Str. 115A
79106 Freiburg
Timme-Bronsert, Sylvia
Universitätsklinikum Freiburg, Department für Pathologie, Institut für Klinische Pathologie
Breisacher Str. 115A
79106 Freiburg
DCIS, PHH3, LDH5, Immunohistochemistry, clinical implications
Background: Proliferation and pre-malignancy are typical features of DCIS. The expression of PHH3 as a marker for proliferation and LDH 5 as an indicator for oxygen independent energy metabolism was investigated in order to assess their potential for an improved characterisation of these lesions.
Methods: Archived tissue blocks and clinical records of 130 patients with DCIS. Immunohistochemistry for PHH3, LDH5, estrogen receptor (ER), progesterone receptor (PR), human EGF receptor 2 (HER2). Silverstein nuclear grading. Chi Square test for all factors.
Results: Percentage of positive patients was 69% for PHH3, 94% for LDH5, 76% for ER, 67% for PR, and 21% for HER2. Significant correlation was seen between PHH3 and LDH5 expression. No correlation could be found for any of the other comparisons.
Conclusion: This is the first description of PHH3 and LDH5 in DCIS. The biological significance of PHH3 remains to be determined in a larger set ofpatients. LDH5 may be a useful diagnostic marker in the future. Positive HER2 receptors were considerably less frequent than previously reported.
DiagnomX GmbH
2017-02-09 12:31:05
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/241
Diagnostic Pathology; Vol 3 No 1 (2017): 2017
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/209
2018-06-19T09:00:47Z
dpath:RES
"160919 2016 eng "
2364-4893
dc
Automatic quantification of the microvascular density on whole slide images, applied to paediatric brain tumours
Deroulers, Christophe
Univ Paris Diderot-Paris 7, Laboratoire IMNC, UMR 8165 CNRS, Univ Paris-Sud, F-91405 Orsay http://www.imnc.in2p3.fr/pagesperso/deroulers/
Dangouloff-Ros, Volodia
Department of Paediatric Radiology, Hopital Necker Enfants Malades, AP-HP, F-75105 Paris, and INSERM U1000, Paris
Badoual, Mathilde
Univ Paris Diderot, Laboratoire IMNC, UMR 8165 CNRS, Univ Paris-Sud, F-91405 Orsay
Varlet, Pascale
Department of Neuropathology, Centre Hospitalier Sainte-Anne, Paris, and INSERM U1000, Paris, and Univ Paris Descartes, Paris
Boddaert, Nathalie
Department of Paediatric Radiology, Hopital Necker Enfants Malades, AP-HP, F-75105 Paris, and INSERM U1000, Paris, and Univ Paris Descartes, Paris, and UMR 1163, Institut Imagine, Paris
Digital Pathology; Image Processing; Whole Slide Images; Angiogenesis; Microvessels; Brain Tumour
Background
Angiogenesis is a key phenomenon for tumour progression, diagnosis and treatment in brain tumours and more generally in oncology. Presently, its precise, direct quantitative assessment can only be done on whole tissue sections immunostained to reveal vascular endothelial cells. But this is a tremendous task for the pathologist and a challenge for the computer since digitised whole tissue sections, whole slide mages (WSI), contain typically around ten gigapixels.
Methods
We define and implement an algorithm that determines automatically, on a WSI at objective magnification 40x, the regions of tissue, the regions without blur and the regions of large puddles of red blood cells, and constructs the mask of blur-free, significant tissue on the WSI. Then it calibrates automatically the optical density ratios of the immunostaining of the vessel walls and of the counterstaining, performs a colour deconvolution inside the regions of blur-free tissue, and finds the vessel walls inside these regions by selecting, on the image resulting from the colour deconvolution, zones which satisfy a double-threshold criterion. The two thresholds involved are automatically computed from the WSI so as to cope with variations in staining and digitisation parameters. A mask of vessel wall regions on the WSI is produced. The density of microvessels is finally computed as the fraction of the area of significant tissue which is occupied by vessel walls. We apply this algorithm to a set of 186 WSI of paediatric brain tumours from World Health Organisation grades I to IV.
Results
The algorithm and its implementation are able to distinguish on the WSI the significant tissue and the vessel walls. The segmentations are of very good quality although the set of slides is very heterogeneous (in tumour type, in staining and digitisation parameters, and inside WSI themselves, where the tissue was often very fragmented). The computation time is of the order of a fraction of an hour for each WSI even though a modest desktop computer is used (a 2012 Mac mini) and the average size of WSI is 7Â gigapixels. The computed microvascular density is found to be robust. We find that it strongly correlates with the tumour grade.
Conclusions
We have introduced a method of automatic segmentation of significant, blur-free tissue and of vessel walls, and of quantification of the density of microvessels, in WSI. We successfully tested it on a large variety of brain tumour tissue samples. This method requires no training and estimates automatically several important parameters of the segmentation. It is robust and can easily be applied to other tumour types and other stainings. It should improve the reproducibility of quantitative estimates in pathology while sparing the pathologist time and effort.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/209
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/280
2020-12-16T19:42:53Z
dpath:RES
"201216 2020 eng "
2364-4893
dc
From COVID-19 Infection to social level disease (SLD)
Kayser, Klaus
Charite - Berlin
Rottmann, Norbert
AIM: To analyse, diagnose, and forecast the development of the pandemic Corona disease and to transfer the data into a corresponding virtual ‘orders of structure system’.
Background: COVID-19 pandemic is a RNA virus transmitted human respiratory tract infection of moderate to high infection rate (20 % – 40 %) and a case fatality ratio of 2 % – 5 %. The infection rate depends upon age and health condition of exposed persons, density of virus droplets, air temperature, legal regulations as well as social life style and behaviour.
Stage of prevention: The high modulation rate of virus RNA and its protein structure require protective strategies at cellular and macromolecule level (preventive immunization), individual protection (personal risk) such as mouth masks, strict regulations of the social behaviour, shutdown of restaurants, hotels, of travel, public demonstrations, private festivals, etc. Legal regulations often hinder the state and federal government from acting in fully restrictive manner. Numerous citizens are not convinced of the ordered restrictions. They fear severe damage to their ‘freedom’ and economic situation. Therefore, COVID-19 also causes a social level disease (SLD), and should be diagnosed and treated accordingly.
Explanation and diagnosis of a social level disease (SLD): Nature has organized human life in ordered communicative structures which can be represented by horizontal and vertical coordinates. Horizontally arranged neighbouring structures can often replace damaged or lost structures, in contrast to vertical structures. External interaction, forecast and potential repair of involved structures require statistical algorithms. Calculation of entropy at different structure levels is a useful tool to forecast the disease’s course.
Conclusions and advices: COVID-19 disease is primarily a RNA virus infection which starts at low level structures (macromolecule) and induces alteration of communicative higher order structures. They include primarily pulmonary cells, airways, additional organs, individual persons, human behaviour, profession, trade, organization of societies, states and countries. Severe changes of social behaviour and civil laws are unavoidable consequences. They belong to basic natural laws of communication, droplet distribution, decay of infectious agents and individual protection.
DiagnomX GmbH
2020-02-23 17:14:54
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/280
Diagnostic Pathology; Vol 6 No 1 (2020): Vol 6 No 1
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/112
2019-08-22T16:07:58Z
dpath:RES
"160617 2016 eng "
2364-4893
dc
Comparing Conventional and Telepathological Diagnosis in Routine Frozen Section Service
Hufnagl, Peter
Charité - Universitätsmedizin Berlin
Guski, Hans
Charité - Universitätsmedizin Berlin
Hering, Jörg
Vivantes Clinic Berlin
Schrader, Thomas
University of Applied Sciences, Brandenburg
Kayser, Klaus
Charité - Universitätsmedizin Berlin
Tennstedt-Schenck, Cornelia
Practice for Pathology Mühlhausen
Dietel, Manfred
Charité - Universitätsmedizin Berlin
Winzer, Klaus-Jürgen
Charité - Universitätsmedizin Berlin
Frozen section service, Telepathology, Remote telemicroscopy, Breast surgery, Randomised study
Aims: In a prospective randomised study the diagnostic accuracy of frozen section service of conventional and telepathological procedures was compared for routine breast surgery.
Material and Methods:In the telepathological approach the surgeon performed the gross examination and macroscopic cutting directly supervised via videoconference by a pathologist. Then a technician prepared the frozen sections and the staining. The on-line histological diagnosis was done using a remote controlled robotic microscope. The images were transferred to the computer screen of the pathologist. In the conventional mode, the pathologist himself manually performed the gross and microscopic tissue examination in the same laboratory. The material was restricted to breast specimens and the number of participating surgeons was limited in order to obtain comparable results. All in all, 81 routine frozen sections of the breast were included in the study within seven months.
Results: The overall diagnostic concordance of both approaches with the definite diagnosis based upon paraffin embedded tissue was calculated to 95,1 % (77/81 cases). The telepathology arm revealed 94,3 % (33/ 35 cases), and the conventional arm 95,7% (44/46 cases). Two cases of each arm remained uncertain. The median diagnostic time was calculated to 9 minutes in the conventional mode and to 17 minutes for telepathology. Not included are median 3 minutes for transportation and 12 minutes for slide preparation.
Discussion: Telepathology can replace successfully conventional performance of frozen section service within the same range of diagnostic accuracy.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/112
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/254
2019-08-22T15:38:41Z
dpath:RES
"171216 2017 eng "
2364-4893
dc
Predatory Journals, Science Citation Index and Open Access Publications in Diagnostic Pathology
Kayser, Klaus
Charite - Berlin
Borkenfeld, Stephan
IAT, Heidelberg, Germany
Kayser, Gian
Institute of Surgical Pathology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Background: Predatory behavior in open access peer reviewed scientific journals seems to be increasing. It is subject to serious discussions between editors, authors, and publishers. Herein we discuss some characteristics of electronic communication in science, the reasons for potential misuse, and present some entropy calculations.
Theoretical considerations: Publication of research articles uses visual information transfer, and seldom acoustic communication. Advantages of open access electronic journals include prompt and worldwide distribution, free access, and several free re-use rights. Disadvantages might be seen in non congruent business models of authors and publishers, which include impact of financial issues on scientific quality and easy to perform, hard to detect manipulation of published data and their sources.
Present stage: Citation Index (SI) and Journal Impact Factor (JIP) are the principal sources which are thought to guarantee the article’s quality and author’s prestige. Authors try to publish in and publishers try to offer journals with high SI and JIP. Independent review processes should serve to maintain the article’s quality. Reviewers are invited electronically in both conventional paper printed and electronically distributed journals. They are requested to act at their earliest convenience. Reviews are as all fast electronic information distribution exposed to become manipulated, in politics, commerce, and science as well.
Proposal and perspectives:Electronic information exchange uses properties of virtual reality, which include the reversibility of time. They are scalable events and can be measured by an appropriate entropy concept. Authors can be considered information source that should be understood by the readers (receiver). The higher the information content the more precise is the reaction of the receiver. The readers’ reaction can be measured and be used to classify, modify, correct, or even erase the distributed information. The development of appropriate readers’ tools would improve the quality and originality of the article and journal.
Conclusion: A readers’ oriented model would be an appropriate extension of quality assurance for open access journals and articles. Such a model could be based upon the entropy concept and be a reliable measure of research quality and impact on its future development.
DiagnomX GmbH
2017-02-09 12:31:05
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/254
Diagnostic Pathology; Vol 3 No 1 (2017): 2017
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/66
2018-06-19T09:01:16Z
dpath:RES
"150905 2015 eng "
2364-4893
dc
The detection of human papilloma virus 16 L1 capsid protein and p16 in cervical lesions
Uranbolor, Jugder
Erdenetsogt, Dongobat
Galtsog, Lodon
Sarantuya, Jav
Immunohistochemistry; Human papillomavirus; Cervical cancer; p16
Background
Cervical cancer is the second most common type of cancer in women worldwide and also the second most common female malignancy in Mongolia. The association of p16 and hr-HPV in Asia and in more particular in Mongolia are still relatively unexplored. So we aimed to detect the immunohistochemistry expression of p16 and L1 protein of HPV16 and to investigate the combined expression of these markers in cervical lesions.
Methods
A total of 96 cases were selected from the records of Pathology services, National Cancer center of Mongolia. There were 50 cases diagnosed as LSIL and 46 cases diagnosed as HSIL. The immunohistochemical staining with p16 and HPV 16 L1 were done on all cases.
Results
The positive rate of HPV 16 L1 capsid protein was identified 74% in LSIL cases and 52% in HSIL cases.There were a significant difference for HPV16 in HSIL and LSIL groups.Immunohistochemistry of p16 staining shows 76% in LSIL cases and 72% in HSIL cases. There was not a statistically significant difference for p16 in HSIL and LSIL groups. A chi square test was used to analyze the result and the obtained p value was <0.05.
Conclusion
The combination between hr-HPV and p16 is considered to be more useful, having a higher accuracy than hr-HPV or p16 alone. There is still critical need, to find other molecular surrogate markers, which can provide accurate information about which precursor lesions would progress toward cancer.Â
DiagnomX GmbH
2015-01-08 17:32:29
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/66
Diagnostic Pathology; 2015
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/246
2019-08-22T15:54:33Z
dpath:RES
"170524 2017 eng "
2364-4893
dc
The long Tramp from Cellular Pathology to Molecular Pathology
Guski, Hans
Background: The Charite is a well known and one of the biggest University Hospital in Germany. Its Institute of Pathology was founded in 1831, and took part in all changes and modifications of diagnostic surgical pathology. Herein, it forms the basis to describe the history and development of molecular pathology from its early beginning. The appearance of biological structures at microscopic levels forms its fundament, similar to additional tissue theories which have been derived from cellular pathology.
Theories of pathology: Theories of pathology frequently describe reaction patterns, and try to explain the relationship between disease and its visible manifestation. They have entered pathology in the 20th century. To name some of them: theory of inflammation [Heinrich Schade 1924, [1], pathology of relations [Gustav Ricker (1924), [2], intercellular pathology [Tivadar Huzella (1937), [3].
Derivatives: The observation of principal identity of biological meaningful elements can be agglutinated to a ‘general theory of live’ and its manifestation. All of the investigated elements posses the same regularities, which are altered, destroyed or newly built by external influences such as disease, physical and psychological forces. Not all magnification levels that display with these elements are of the same significance. Already Virchow suggested that ‘smaller elements (molecules) might be responsible for changes that are visible ‘in larger elements’ (at cellular level). The reflection on these ideas can be associated with the implementation of molecular techniques which has been developed in the 20th century and are still ongoing today. Perspectives: Thus, cellular and molecular pathology can be integrated under one umbrella. This umbrella will lead to newly man-formed structures, such as artificial DNA and gene components or functional chip implantations.
DiagnomX GmbH
2017-02-09 12:31:05
application/pdf
application/xml
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/246
Diagnostic Pathology; Vol 3 No 1 (2017): 2017
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/231
2018-06-19T08:55:24Z
dpath:RES
"161107 2016 eng "
2364-4893
dc
The Technicians´ Role in Digital Pathology Implementation. Searching Optimization.
Alcaraz Mateos, Eduardo
Pathology Department, Morales Meseguer University Hospital, Murcia, Spain.
Tortosa-MartÃnez, Inmaculada
Pathology Department, Morales Meseguer University Hospital, Murcia, Spain.
Alcolea-Guardiola, Carlos
Pathology Department, Morales Meseguer University Hospital, Murcia, Spain.
Estévez-Ligero, Susana
Pathology Department, Morales Meseguer University Hospital, Murcia, Spain
Abellán-Palazón, Ãngeles
Pathology Department, Morales Meseguer University Hospital, Murcia, Spain
Kundisova, Alexandra
Faculty of Medicine, University of Bratislava, Slovakia
Nieto-Olivares, Andrés
Pathology Department, Morales Meseguer University Hospital, Murcia, Spain
Chaves-Benito, Asunción
Pathology Department, Morales Meseguer University Hospital, Murcia, Spain
Poblet, Enrique
Pathology Department, Reina SofÃa University Hospital, Murcia, Spain.
Digital Pathology; Histotechnician; Pathology Assistant; Resource Optimization.
Background
Scanning histological or cytological preparations is a crucial element in the process of digitization of Pathology Departments, along with the traceability of tissue samples and the reports management. The scanning time and the high size of the files are still considered suboptimal for full implementation. In order to optimize time and space a comparative study of the workflow performed by histotechnicians in our center has been carried out.
Material & Methods
A total of 25 endoscopic samples were selected with the intention of comparing different parameters (scanning time, error rate during scanning and hard disk storage) between the original histological glass slides (group A: 2 slides per case, 50 preparations) and new sections, with levels grouped into a single slide (group B: 1 slide per case, 25 preparations). They were scanned at 20x magnification in routine way using the Ventana iScan Coreo scanner (Roche diagnostics). The process was repeated 4 times to calculate averages.
Results
The average scanning time was 5 hours 40 minutes (6m 48s / slide) in group A and 5 hours 10 minutes (12m 24s / slide) in group B. The error rate was 6.1% in group A and 3,8% in group B. The space occupied on the hard disk was 11.87 GB in group A and 9.6 GB in group B (475 MB/case vs 385 MB/case, respectively). The average number of tissue sections per case was 7 in group A and 8 in group B.
Conclusion
There is a clear benefit of standardizing and optimizing the number of cuts per slide in terms of storage (saving 19%), biopsy sampling (14% more tissue) and error rate (37% less), including a not negligible decrease in the scanning time (9%) in the study conducted.
DiagnomX GmbH
2016-01-17 11:46:24
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/231
Diagnostic Pathology; Vol 2 No 1 (2016): 2016
eng
##submission.copyrightStatement##
oai:ojs2.localhost:article/283
2021-03-12T16:03:17Z
dpath:RES
"210220 2021 eng "
2364-4893
dc
VHL expression level in the pathological tissue is significantly associated with clinical outcomes of platinum-based chemotherapy in non-small cell lung cancer patients. (withdrawn 03/11/2021)
Cao, yejun
East Hospital, Tongji University School of Medicine
Wang, Lingwei
Zhang, Qiying
Han, Yang
Ma, Liang
Liu, Jie
Wang, Jinyi
Sun, Zhengliang
Zhao, Tian
Chen, Guohan
Hong, Xuan
Objective To investigate the association between expression level of VHL in pathological tissue and outcomes of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients. Methods The pathological samples of NSCLC patients were obtained for immunohistochemical staining to evaluate the expression level of VHL. Furthermore, their clinical data were collected and prognosis was traced by phone. The correlation between gene expression level and the hematotoxicity was evaluated by chi-square test. The influence of VHL expression level on the risk of hematotoxicity was tested by logistic regression model. The survival curve was plotted by Kaplan-Meier method and the survival rate between the two groups was compared by log-rank test. Results A total of 110 NSCLC patients were enrolled in this study, the median follow-up time of these patients was 27.5 months. In the whole group, 31 patients had died by the last date of follow-up to get their survival information (Nov.10,2020), with a median survival time of 24.3 months. Though immunohistochemical analysis,we found that 59 patients(53.6%) had weak expression level of VHL or lack of expression in their tumor tissues,while 51 patients(46.4%) presented moderate or high expression. We found that the patients with weak expression of VHL in their carcinoma tissue or lack of expression had more opportunities to occur neutropenia after platinum-based chemotherapy(OR=0.264,95%CI=0.085-0.818,P-value=0.021).And the expression level of VHL was correlated with OS(Logrank test:P-value= 0.007,HR= 4.219,95%CI: 1.75-10.174, P-value=0.001), while not related with DFS(Logrank test:P-value=0.256,HR= 1.334,95%CI:0.642-2.769, P-value=0.440). Conclusion The expression level of VHL gene in pathological tissue is related with Granulocytosis and leukocytotoxicity after platinum-based chemotherapy in NSCLC patients. It can be used as a biomarker to predict the risk of neutropenia and the prognosis of NSCLC patients.
DiagnomX GmbH
2020-02-23 17:14:54
application/pdf
http://www.diagnosticpathology.eu/content/index.php/dpath/article/view/283
Diagnostic Pathology; Vol 6 No 1 (2020): Vol 6 No 1
eng
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