Diagnostic pathology - editorial.
Explore the source record for details and available documents.
Editorial↗
Biomedical subjects
Klaus Kayser
Publications and source records attributed to Klaus Kayser.
Mobile education in autopsy conferences of pathology: presentation of complex cases.
BACKGROUND: MeduMobile was a project to develop and evaluate learning scenarios for medical students and teachers by use of video communication and notebooks. Its core part was assigned to various medical routines, conferences or meetings such as doctor-patient bedside conversation. These were filmed by video teams and broadcasted live via the WLAN of the Charité campus to course participating students. One type of the learning arrangements was the autopsy conference as an on-call scenario. MATERIALS AND METHODS: The MeduMobile project consisted of two main compartments: the regular seminar event which took place every week or month, and the on-call event. For an on-call event the students were informed two hours before the lesson's start. A mobile video team organised the video conference via a specific MeduMobile seminar system. This software offered the students to log. The MeduMobile seminar system is based on the Windows operating system and realises an extended video communication via WLAN. Thirteen access points were implemented at the Charité Campus Virchow Klinikum and Campus Mitte. A questionnaire was developed to investigate in the response and learning effect of the mobile seminar system. RESULTS: During the MeduMobile project 42 video conferences with (cumulative) 145 participating students took place. Four autopsy conferences could be organised as on-call scenarios within this project. A prospective, not randomised follow-up study was included 25 students of the 1st - 6th clinical semester. According to the answers, professional reasoning, professional performance, sustainability, and the complexity were broadly accepted by the students. DISCUSSION: In principle, the MeduMobile realised an interdisciplinary case presentation using video conference and web page. The evaluation indicates a high acception of such complex case presentation with multidisciplinary settings. The use of the notebooks in mobile learning enables an interconnective training and promotes a complex learning.
Journal Article↗
The diagnostic path, a useful visualisation tool in virtual microscopy.
BACKGROUND: The Virtual Microscopy based on completely digitalised histological slide. Concerning this digitalisation many new features in mircoscopy can be processed by the computer. New applications are possible or old, well known techniques of image analyses can be adapted for routine use. AIMS: A so called diagnostic path observes in the way of a professional sees through a histological virtual slide combined with the text information of the dictation process. This feature can be used for image retrieval, quality assurance or for educational purpose. MATERIALS AND METHODS: The diagnostic path implements a metadata structure of image information. It stores and processes the different images seen by a pathologist during his "slide viewing" and the obtained image sequence ("observation path"). Contemporary, the structural details of the pathology reports were analysed. The results were transferred into an XML structure. Based on this structure, a report editor and a search function were implemented. The report editor compiles the "diagnostic path", which is the connection from the image viewing sequence ("observation path") and the oral report sequence of the findings ("dictation path"). The time set ups of speech and image viewing serve for the link between the two sequences. The search tool uses the obtained diagnostic path. It allows the user to search for particular histological hallmarks in pathology reports and in the corresponding images. RESULTS: The new algorithm was tested on 50 pathology reports and 74 attached histological images. The creation of a new individual diagnostic path is automatically performed during the routine diagnostic process. The test prototype experienced an insignificant prolongation of the diagnosis procedure (oral case description and stated diagnosis by the pathologist) and a fast and reliable retrieval, especially useful for continuous education and quality control of case description and diagnostic work. DISCUSSION: The Digital Virtual Microscope has been designed to handle 1000 images per day in the daily routine work of a pathology institution. It implies the necessity of an automatic mechanism of image meta dating. The non - deterministic correlation between the oral statements (case report) and image information content guides the image meta dating. The presented software opens up new possibilities for a content oriented search in a virtual slide, and can successfully support medical education and diagnostic quality assurance.
Journal Article↗
Grid technology in tissue-based diagnosis: fundamentals and potential developments.
Tissue-based diagnosis still remains the most reliable and specific diagnostic medical procedure. It is involved in all technological developments in medicine and biology and incorporates tools of quite different applications. These range from molecular genetics to image acquisition and recognition algorithms (for image analysis), or from tissue culture to electronic communication services. Grid technology seems to possess all features to efficiently target specific constellations of an individual patient in order to obtain a detailed and accurate diagnosis in providing all relevant information and references. Grid technology can be briefly explained by so-called nodes that are linked together and share certain communication rules in using open standards. The number of nodes can vary as well as their functionality, depending on the needs of a specific user at a given point in time. In the beginning of grid technology, the nodes were used as supercomputers in combining and enhancing the computation power. At present, at least five different Grid functions can be distinguished, that comprise 1) computation services, 2) data services, 3) application services, 4) information services, and 5) knowledge services. The general structures and functions of a Grid are described, and their potential implementation into virtual tissue-based diagnosis is analyzed. As a result Grid technology offers a new dimension to access distributed information and knowledge and to improving the quality in tissue-based diagnosis and therefore improving the medical quality.
Journal Article↗
Towards an automated virtual slide screening: theoretical considerations and practical experiences of automated tissue-based virtual diagnosis to be implemented in the Internet.
AIMS: To develop and implement an automated virtual slide screening system that distinguishes normal histological findings and several tissue--based crude (texture-based) diagnoses. THEORETICAL CONSIDERATIONS: Virtual slide technology has to handle and transfer images of GB Bytes in size. The performance of tissue based diagnosis can be separated into a) a sampling procedure to allocate the slide area containing the most significant diagnostic information, and b) the evaluation of the diagnosis obtained from the information present in the selected area. Nyquist's theorem that is broadly applied in acoustics, can also serve for quality assurance in image information analysis, especially to preset the accuracy of sampling. Texture-based diagnosis can be performed with recursive formulas that do not require a detailed segmentation procedure. The obtained results will then be transferred into a "self-learning" discrimination system that adjusts itself to changes of image parameters such as brightness, shading, or contrast. METHODS: Non-overlapping compartments of the original virtual slide (image) will be chosen at random and according to Nyquist's theorem (predefined error-rate). The compartments will be standardized by local filter operations, and are subject for texture analysis. The texture analysis is performed on the basis of a recursive formula that computes the median gray value and the local noise distribution. The computations will be performed at different magnifications that are adjusted to the most frequently used objectives (*2, *4.5, *10, *20, *40). The obtained data are statistically analyzed in a hierarchical sequence, and in relation to the clinical significance of the diagnosis. RESULTS: The system has been tested with a total of 896 lung cancer cases that include the diagnoses groups: cohort (1) normal lung--cancer; cancer subdivided: cohort (2) small cell lung cancer--non small cell lung cancer; non small cell lung cancer subdivided: cohort (3) squamous cell carcinoma--adenocarcinoma--large cell carcinoma. The system can classify all diagnoses of the cohorts (1) and (2) correctly in 100%, those of cohort (3) in more than 95%. The percentage of the selected area can be limited to only 10% of the original image without any increased error rate. CONCLUSION: The developed system is a fast and reliable procedure to fulfill all requirements for an automated "pre-screening" of virtual slides in lung pathology.
Journal Article↗
Lack of CD117 and rare bcl-2 expression in stomach cancer by immunohistochemistry. An immunohistochemical study with review of the literature.
BACKGROUND: Gastric adenocarcinoma is one of the most frequent malignancies worldwide including Iran. This study was designed to immunohistochemically evaluate the CD117 and bcl-2 expression in gastric carcinomas and their potential use as therapeutic targets in the treatment of patients with advanced stage gastric cancer. MATERIALS AND METHODS: Representative paraffin blocks obtained from 38 operated gastric adenocarcinoma patients were retrieved from Afzalipour Hospital pathology department archive, Kerman, Iran. Immunohistochemical analysis (IHC) for CD117 was carried out in all cases including negative (normal gastric epithelium) and positive (Gastrointestinal Stromal Tumor) controls. In addition, the cases were evaluated immunohistochemically for apoptosis-related protein (bcl-2), to evaluating a potential association of CD117 expression with the cell proliferation regulatory pathways. RESULTS: No positive reaction for CD117 was seen in gastric carcinoma tumor cells irrespective to the cell type, grade, and stage, proliferation and apoptosis rate. Expression of bcl-2 was observed in only one case. CONCLUSION: We conclude that CD117 overexpression detectable by immunohistochemistry does not play a significant role in gastric carcinoma pathways and development, although overexpression at the gene level and/or mutated CD117 expression might exist. Thus, it is unlikely that the CD117 pathway is of clinical significance in gastric carcinoma patients.
Journal Article↗
[Prognostic role of microvascularization in surgically treated lung cancer].
OBJECTIVE: The aim of our study was the determination of microvascularization and its prognostic significance in lung cancer patients. METHODS: Histological sections were prepared from paraffin-embedded tissues removed from the peripheral part of the tumor of 450 radically operated non-small cell and small cell lung cancer patients. Immunohistochemical staining was performed with antibody against factor VIII-associated antigen. During computer imaging, the absolute and relative parameters of vascularization were determined, as was the density of tumor cells situated to the nearest neighboring vessels. The results were compared with TNM status, the cell type and survival. RESULTS: T2 and T4 tumors demonstrated an enhanced vascularization, however, except for the surface fraction, statistically significant difference was not found. The microvascularization parameters did not differ significantly between tumors with different N status. In small cell lung cancer cases, the vascularization was stronger than in non-small cell lung cancer cases, while cell density was lower, however, these differences did not prove statistically significant. The survival rate decreased significantly with the increasing tumor cell density in the interval of 0-20 microm. CONCLUSIONS: A clear connection could not be demonstrated between vascularization and the appearance of lymph node metastases. The density of tumor cells measured in the direct vicinity of vessels proved an important prognostic factor.
Aged↗
Introducing Diagnostic Pathology.
Explore the source record for details and available documents.
Editorial↗
Theory and implementation of an electronic, automated measurement system for images obtained from immunohistochemically stained slides.
OBJECTIVE: To develop and implement an Internet-based, automated image measurement system for immunohistochemically stained slides including fluorescence images in online and off-line modes. STUDY DESIGN: An image analyzing system was developed that automatically measures digitized images obtained from immunohistochemically stained slides. It is divided into a common server platform and a specific image quantification system based upon DIAS (University of Jena). After registration, the user fills in an input data form and attaches images to be measured. The server periodically transfers the data to the measurement system. The measurement works on dynamic thresholding and active sampling of objects visualized by fluorescence and conventional chromogens. It includes stereologic algorithms, object quantification, syntactic structure analysis and quality assurance. RESULTS: The system has been tested for diaminobenzidene, alkaline phosphatase and fluorescence images (FITC, etc.). The reproducibility and stability of the system are > 98%. The series of successfully measured images comprises > 1,000 images in total in the online and off-line modes. CONCLUSION: An Internet-based automated image measurement system has been developed that offers worldwide access to the major requests for quantification of immunohistochemically stained slides-tissue array analysis, nuclear stains (MIB, hormones), membrane stains (CerbB2), vascularization and fluorescence in situ hybridization.
Anatomy, Cross-Sectional↗
Cystatins in non-small cell lung cancer: tissue levels, localization and relation to prognosis.
Cystatins regulate tumour-associated cysteine proteases, however, their role in tumour progression is not clear yet. To assess their relevance in the progression of non-small cell lung cancer (NSCLC) the protein level, cysteine protease activity (CPI) and localization of type I (stefins A and B) and type II (C, E/M and F) cystatins were defined in tumours and control lung counterparts from 165 patients. The medians of CPI activity, stefins A and B were significantly greater in tumour than in lung tissue (2.1-fold, 1.7-fold, 1.2-fold, respectively, all p<0.001). The median levels of cystatin C and cystatin E/M were lower in tumour tissue (0.9-fold, p=0.06; 0.6-fold, p<0.01). In all the samples the levels of cystatin F were below the detection limit. Immunohistochemical analysis revealed the presence of all cystatins in tumour cells and infiltrated inflammatory cells such as macrophages and neutrophils. In univariate survival analysis patients with high levels of stefin A, stefin B and CPI activity exhibited a better survival probability (p=0.05, p=0.05, p<0.01, respectively). In contrast, cystatins C and E/M provided no prognostic information. In multivariate analysis the most powerful predictor of survival was the pTNM stage (p<0.0001; RR 3.5), followed by stefin A, stefin B and CPI activity (all p=0.03; RR 1.5). Our results suggest that only stefins A and B, i.e. type I cystatins, are up-regulated in lung tumours and thus able to counteract harmful tumour-associated proteolytic activity. As biological markers they may add independent prognostic information for better assessment of low- and high-risk patients with NSCLC.
Adolescent↗
Localized fibrous tumors (LFTs) of the pleura: clinical data, asbestos burden, and syntactic structure analysis applied to newly defined angiogenic/growth-regulatory effectors.
This study was performed to add clinical data, to introduce new markers, and to perform syntactic structural analysis on localized fibrous tumors (LFTs) of the pleura. The material comprised clinical data and processed sections obtained from 36 patients. The results achieved from quantitative imaging techniques and syntactic structure analysis were correlated with clinical data, including patients' habits (smoking), asbestos exposure, survival, and tumor recurrence. The disease caused increasing chest pain and dyspnea in 47% of patients. Exposure to asbestos was noted in 13 out of 36 patients, whereas smoking posed no major risk factor. Two patients developed a recurrent tumor after 8 and 42 months, respectively; none of the other patients died of this tumor disease within the follow-up period of maximal 212 months. The cases were clearly discriminated from mesotheliomas by the marker profile. Frequent expression of accessible ligands for endogenous lectins galectins-1 and -3, the expression of the angiogenic macrophage migration inhibitory factor (MIF), and the dense vascularization intimate a functional relationship. The proliferation index (Nv) was computed to be 1.6% in line with the balance of galectin expression. Abnormal p53 was expressed in only 19.4% of the cases. The diagnosis of LFT can be aided by quantitative assessment of vimentin, CD34, MIF, vascularization, and proliferation. Considering the galectin network, differential expression was noted with preference to effectors limiting growth and aggressiveness.
Adult↗
Prognostic significance of endogenous adhesion/growth-regulatory lectins in lung cancer.
OBJECTIVE: To determine the expression of endogenous adhesion/growth-regulatory lectins and their binding sites using labeled tissue lectins as well as the binding profile of hyaluronic acid as an approach to define new prognostic markers. METHODS: Sections of paraffin-embedded histological material of 481 lungs from lung tumor patients following radical lung excision processed by a routine immunohistochemical method (avidin-biotin labeling, DAB chromogen). Specific antibodies against galectins-1 and -3 and the heparin-binding lectin were tested. Staining by labeled galectins and hyaluronic acid was similarly visualized by a routine protocol. After semiquantitative assessment of staining, the results were compared with the pT and pN stages and the histological type. Survival was calculated by univariate and multivariate methods. RESULTS: Binding of galectin-1 and its expression tended to increase, whereas the parameters for galectin-3 decreased in advanced pT and pN stages at a statistically significant level. The number of positive cases was considerably smaller among the cases with small cell lung cancer than in the group with non-small-cell lung cancer, among which adenocarcinomas figured prominently with the exception of galectin-1 expression. Kaplan-Meier computations revealed that the survival rate of patients with galectin-3-binding or galectin-1-expressing tumors was significantly poorer than that of the negative cases. In the multivariate calculations of survival lymph node metastases (p < 0.0001), histological type (p = 0.003), galectin-3-binding capacity (p = 0.01), galectin-3 expression (p = 0.03) and pT status (p = 0.003) proved to be independent prognostic factors, not correlated with the pN stage. CONCLUSION: The expression and the capacity to bind the adhesion/growth regulatory galectin-3 is defined as an unfavorable prognostic factor not correlated with the pTN stage.
Aged↗
Numerical and structural centrosome aberrations are an early and stable event in the adenoma-carcinoma sequence of colorectal carcinomas.
AIMS: Numerical and structural centrosome changes have been described for and linked with genetic instability in solid tumors. Here, we specifically address centrosome aberrations in the adenoma-carcinoma sequence of colorectal cancer by detailed evaluation of gamma-tubulin staining patterns. METHODS: Formalin-fixed and paraffin-embedded specimens (normal colonic epithelium n=21; low-grade intraepithelial neoplasia n=27, high-grade intraepithelial neoplasia n=16 and invasive adenocarcinomas n=33) were stained by an anti-gamma-tubulin antibody using standard immunofluorescence. Three-dimensional image stacks of the stainings were recorded (Zeiss LSM510 confocal microscope), followed by numerical and structural data analysis (DIAS software package) and statistical evaluation (NCSS-software). RESULTS: The mean centrosome signal per cell differed significantly (P<0.0001) between normal colonic epithelium (0.8775) and each low-grade intraepithelial neoplasia (1.787), high-grade intraepithelial neoplasia (2.259) and invasive carcinomas (2.267). Similarly, both the centrosomes' structural entropy (SE) and minimal spanning tree (MST) differed significantly (P<0.001) between normal (SE=3.956, MST=38.78) and each low- (SE=6.39, MST=26) and high-grade intraepithelial neoplasia (SE=5.75, MST=26.97) and invasive carcinoma (SE=6.86, MST=28.08). CONCLUSION: Numerical and structural centrosome dysregulation is seen as early as in low-grade dysplastic lesions of the adenoma-carcinoma sequence of colorectal carcinomas and may, as such, play an initial role in the carcinogenic process.
Adenocarcinoma↗
Prognostic significance of microvascularization in cases of operated lung cancer.
OBJECTIVE: Measurement of microvascularization and determination of its prognostic significance in cases of lung cancer. METHODS: Section prepared from histological material from 432 radically operated non-small cell lung cancer patients were stained with antibodies against factor VIII-associated antigen. During computer imaging, the absolute and relative parameters of the vascularization were determined, as was the density of tumour cells situated in the vicinity of the vessels. The results were compared with the TNM status, the cell type and the survival. RESULTS: Each parameter demonstrated an enhanced vascularization in classifications T2 and T4, but only the surface fraction, the mean vascular circumference and the mean vascular area displayed a significant change. The microvascularization parameters did not differ significantly between with different N status, however, the cell density progressively increased in the areas close to the vessels in advanced pN classifications. Elevation of the tumour cell density within 20 microm distance of the vessels was accompanied by a significantly poorer survival rate. The density of tumour cells within 20 microm region was the second strongest prognostic factor after the N status. CONCLUSIONS: More advanced tumour classifications grow with enhanced vascularization. A clear-cut connection cannot be demonstrated between the vascularization and appearance of lymph node metastases. The density of tumour cells measured in the direct vicinity of vessels is an important prognostic factor.
Adenocarcinoma↗
Highly focused T cell responses in latent human pulmonary Mycobacterium tuberculosis infection.
The elucidation of the molecular and immunological mechanisms mediating maintenance of latency in human tuberculosis aids to develop more effective vaccines and to define biologically meaningful markers for immune protection. We analyzed granuloma-associated lymphocytes (GALs) from human lung biopsies of five patients with latent Mycobacterium tuberculosis (MTB) infection. MTB CD4+ and CD8+ T cell response was highly focused in the lung, distinct from PBL, as assessed by TCR-CDR3 spectratyping coupled with a quantitative analysis of TCR VB frequencies. GALs produced IFN-gamma in response to autologous macrophages infected with MTB and to defined MTB-derived HLA-A2-presented peptides Ag85a242-250, Ag85b199-207, early secreted antigenic target 6 (ESAT-6)28-36, 19-kDa Ag88-97, or the HLA-DR-presented ESAT-6(1-20) epitope. Immune recognition of naturally processed and presented MTB epitopes or the peptide ESAT-6(1-20) could be linked to specific TCR VB families, and in two patients to unique T cell clones that constituted 19 and 27%, respectively, of the CD4+ and 17% of the CD8+ GAL population. In situ examination of MTB-reactive GALs by tetramer in situ staining and confocal laser-scanning microscopy consolidates the presence of MHC class I-restricted CD8+ T cells in MTB granuloma lesions and supports the notion that clonally expanded T cells are crucial in immune surveillance against MTB.
Amino Acid Sequence↗
Lung carcinoma-associated atypical adenomatoid hyperplasia, squamous cell dysplasia, and chromosome alterations in non-neoplastic bronchial mucosa.
This article analyzes phenotype and genotype alterations of the lung in association with lung cancer. The frequency of phenotype preneoplastic lesions (atypical adenomatoid hyperplasia (AAH) and squamous cell dysplasia (SCD)) was analyzed at distinct distances from the tumor boundary in 150 lung carcinomas. AAH was noted in 19/150 (13%) cases and more frequently seen in adeno carcinomas, squamous cell dysplasia was noted in 46/150 (31%) cases and more frequently seen in squamous cell carcinomas. The degree of cellular atypia decreased with increasing distance from tumor boundary in both AAH and SCD. At similar distances, genotype (chromosome) alterations of surrounding bronchial mucosa were studied in additional 55 primary and secondary lung tumors by karyotype analysis. Numerical chromosome aberrations occur frequently in primary lung carcinomas and adjacent bronchial mucosa, and affect at average 4.5/10 metaphases in primary lung cancer and 2/10 metaphases in metastases. Most abnormal metaphases were induced by chromosome losses, only few by additional copies, i.e. trisomy, etc. Losses of y chromosome were seen in both malignancy and adjacent bronchial mucosa, and interpreted as "tumor related", losses of chromosome 21 in adjacent bronchial mucosa were non-tumor related in adenocarcinoma and metastases, losses of chromosome 19 in adjacent bronchial mucosa occurred independently in squamous cell and large cell carcinomas. The data suggest the hypothesis that preneoplastic lesions in the lung might be partly induced by the tumor itself.
Aged↗
Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer.
Several polymorphisms in DNA repair genes have been reported to be associated with lung cancer risk including XPA (-4G/A), XPD (Lys751Gln and Asp312Asn), XRCC1 (Arg399Gln), APE1 (Asp148Glu) and XRCC3 (Thr241Met). As there is little information on the combined effects of these variants, polymorphisms were analyzed in a case-control study including 463 lung cancer cases [among them 204 adenocarcinoma and 212 squamous cell carcinoma (SCC)] and 460 tumor-free hospital controls. Odds ratios (OR) adjusted for age, gender, smoking and occupational exposure were calculated for the variants alone and combinations thereof. For homozygous individuals carrying the Glu variant of APE1, a protective effect was found (OR = 0.77, CI = 0.51-1.16). Individuals homozygous for the variants XPA (-4A) (OR = 1.53, CI = 0.94-2.5), XPD 751Gln (OR = 1.39, CI = 0.90-2.14) or XRCC3 241Met (OR = 1.29, CI = 0.85-1.98) showed a slightly higher risk for lung cancer overall. In the subgroup of adenocarcinoma cases, adjusted ORs were increased for individuals homozygous for XPA (-4A) (OR = 1.62, CI = 0.91-2.88) and XRCC3 241Met (OR = 1.65; CI = 0.99-2.75). When analyzing the combined effects of variant alleles, 54 patients and controls were identified that were homozygous for two or three of the potential risk alleles [i.e. the variants in nucleotide excision repair, XPA (-4A) and XPD 751Gln, and in homologous recombination, XRCC3-241Met]. ORs were significantly increased when all patients (OR = 2.37; CI = 1.26-4.48), patients with SCC (OR = 2.83; CI = 1.17-6.85) and with adenocarcinoma (OR = 3.05; CI = 1.49-6.23) were analyzed. Combinations of polymorphisms in genes involved in the same repair pathway (XPA + XPD or XRCC1 + APE1) affected lung cancer risk only in patients with SCC. These results indicate that lung cancer risk is only moderately increased by single DNA repair gene variants investigated but it is considerably enhanced by specific combinations of variant alleles. Analyses of additional DNA repair gene interactions in larger population-based studies are warranted for identification of high-risk subjects.
Adenocarcinoma↗
Genotype relationships in the CYP3A locus in Caucasians.
Genetic polymorphisms of the human CYP3A family affect clinical drug efficacy and may modify cancer risk. CYP3A genes show high sequence similarity that had previously lead to misallocation of CYP3A polymorphisms. Recent studies indicated a high degree of or even complete linkage for certain CYP3A alleles. Reliable LightCycler-based genotyping methods were developed and their degree of linkage in a large Caucasian population (n = 1210) investigated. Strong linkage disequilibrium was confirmed between CYP3A4, CYP3A5, and CYP3AP1 (each at P < 10(-5)). Contrary to some previous results claiming complete linkage between the phenotypically relevant CYP3A5*1 and a variant in a pseudogene promoter region CYP3AP1*1 we found among 428 controls (15 of 66) and 782 lung cancer cases (25 of 115) approximately 22% of CYP3AP1*1 carriers to be homozygous for CYP3A5*3 We conclude that contrary to previous assumptions, the CYP3AP1 genotype is not a reliable predictor for CYP3A5 activity.
Alleles↗