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  1. Article: A critical appraisal of the classification of urothelial tumours: time for a review of the evidence and a radical change?

    Harnden, Patricia

    BJU international

    2007  Volume 99, Issue 4, Page(s) 723–725

    MeSH term(s) Carcinoma, Transitional Cell/classification ; Carcinoma, Transitional Cell/pathology ; Humans ; Urinary Bladder Neoplasms/classification ; Urinary Bladder Neoplasms/pathology ; Urothelium/pathology
    Language English
    Publishing date 2007-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 1462191-5
    ISSN 1464-410X ; 1464-4096 ; 1358-8672
    ISSN (online) 1464-410X
    ISSN 1464-4096 ; 1358-8672
    DOI 10.1111/j.1464-410X.2006.06672.x
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    Zs.MO 13: Show issues

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  2. Article ; Online: The accuracy of magnetic resonance imaging (MRI) in predicting the invasion of the tunica albuginea and the urethra during the primary staging of penile cancer.

    Hanchanale, Vishwanath / Yeo, Lehana / Subedi, Nawraj / Smith, Jonathan / Wah, Tze / Harnden, Patricia / Bhattarai, Selina / Chilka, Sameer / Eardley, Ian

    BJU international

    2016  Volume 117, Issue 3, Page(s) 439–443

    Abstract: Objectives: To assess the accuracy of magnetic resonance imaging (MRI) in predicting invasion of the tunica albuginea (TA) and the urethra during the primary staging of penile cancer.: Patients and methods: In all, 104 consecutive patients with ... ...

    Abstract Objectives: To assess the accuracy of magnetic resonance imaging (MRI) in predicting invasion of the tunica albuginea (TA) and the urethra during the primary staging of penile cancer.
    Patients and methods: In all, 104 consecutive patients with clinical T1-T3 penile cancer had a penile MRI as a part of local staging protocol. An artificial erection was induced before MRI by injecting alprostadil (prostaglandin E1 ). Four men with poor quality MRI images were excluded from the study. The preoperative MRI was compared with final histology to assess its accuracy in predicting the invasion of the TA and urethra.
    Results: Data of 100 patients who underwent penile MRI before definitive surgery for invasive penile carcinoma were available for analysis. The mean age was 65 years and number of patients with pathological stage T1, T2 and T3 was 32, 52, and 16, respectively. The sensitivity and specificity of MRI in predicting the invasion of TA and urethra was 82.1% and 73.6%, and 62.5% and 82.1%, respectively. There were no MRI-related complications.
    Conclusions: This study shows that penile MRI is an accurate method for assessing TA invasion but is less sensitive in assessing urethral invasion. These results support the use of MRI in the local staging of penile cancer.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Humans ; Magnetic Resonance Imaging/standards ; Male ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Penile Neoplasms/pathology ; Sensitivity and Specificity ; Urethral Neoplasms/pathology
    Language English
    Publishing date 2016-03
    Publishing country England
    Document type Comparative Study ; Evaluation Studies ; Journal Article
    ZDB-ID 1462191-5
    ISSN 1464-410X ; 1464-4096 ; 1358-8672
    ISSN (online) 1464-410X
    ISSN 1464-4096 ; 1358-8672
    DOI 10.1111/bju.13041
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  3. Article ; Online: Proteomic analysis of formalin-fixed paraffin-embedded renal tissue samples by label-free MS: assessment of overall technical variability and the impact of block age.

    Craven, Rachel A / Cairns, David A / Zougman, Alexandre / Harnden, Patricia / Selby, Peter J / Banks, Rosamonde E

    Proteomics. Clinical applications

    2013  Volume 7, Issue 3-4, Page(s) 273–282

    Abstract: Purpose: Protein profiling of formalin-fixed paraffin-embedded (FFPE) tissues has enormous potential for the discovery and validation of disease biomarkers. The aim of this study was to systematically characterize the effect of length of time of storage ...

    Abstract Purpose: Protein profiling of formalin-fixed paraffin-embedded (FFPE) tissues has enormous potential for the discovery and validation of disease biomarkers. The aim of this study was to systematically characterize the effect of length of time of storage of such tissue blocks in pathology archives on the quality of data produced using label-free MS.
    Experimental design: Normal kidney and clear cell renal cell carcinoma tissues routinely collected up to 10 years prior to analysis were profiled using LC-MS/MS and the data analyzed using MaxQuant. Protein identities and quantification data were analyzed to examine differences between tissue blocks of different ages and assess the impact of technical and biological variability.
    Results: An average of over 2000 proteins was seen in each sample with good reproducibility in terms of proteins identified and quantification for normal kidney tissue, with no significant effect of block age. Greater biological variability was apparent in the renal cell carcinoma tissue, possibly reflecting disease heterogeneity, but again there was good correlation between technical replicates and no significant effect of block age.
    Conclusions and clinical relevance: These results indicate that archival storage time does not have a detrimental effect on protein profiling of FFPE tissues, supporting the use of such tissues in biomarker discovery studies.
    MeSH term(s) Adult ; Aged ; Biomarkers/analysis ; Biomarkers, Tumor/analysis ; Carcinoma, Renal Cell/chemistry ; Chromatography, Liquid ; Female ; Formaldehyde/chemistry ; Humans ; Kidney/chemistry ; Kidney Neoplasms/chemistry ; Male ; Mass Spectrometry ; Middle Aged ; Paraffin Embedding/methods ; Proteome/analysis ; Proteomics ; Time Factors
    Chemical Substances Biomarkers ; Biomarkers, Tumor ; Proteome ; Formaldehyde (1HG84L3525)
    Language English
    Publishing date 2013-03-06
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2261788-7
    ISSN 1862-8354 ; 1862-8346
    ISSN (online) 1862-8354
    ISSN 1862-8346
    DOI 10.1002/prca.201200065
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  4. Article ; Online: FGFR3 expression in primary invasive bladder cancers and matched lymph node metastases.

    Turo, Rafal / Harnden, Patricia / Thygesen, Helene / Fleischmann, Achim / Thalmann, George N / Seiler, Roland / Cross, William R / Knowles, Margaret A

    The Journal of urology

    2015  Volume 193, Issue 1, Page(s) 325–330

    Abstract: Purpose: FGFR3 is considered a good therapeutic target for bladder cancer. However, to our knowledge it is unknown whether the FGFR3 status of primary tumors is a surrogate for related metastases, which must be targeted by FGFR targeted systemic ... ...

    Abstract Purpose: FGFR3 is considered a good therapeutic target for bladder cancer. However, to our knowledge it is unknown whether the FGFR3 status of primary tumors is a surrogate for related metastases, which must be targeted by FGFR targeted systemic therapies. We assessed FGFR3 protein expression in primary bladder tumors and matched nodal metastases.
    Materials and methods: We examined matched primary tumor and nodal metastases from 150 patients with bladder cancer clinically staged as N0M0. Four samples per patient were incorporated into a tissue microarray and FGFR3 expression was assessed by immunohistochemistry. FGFR3 expression was tested for an association with categorical clinical data using the Fisher exact test, and with overall and recurrence-free survival by Kaplan-Meier analysis.
    Results: Duplicate spots from primary tumors and lymph node metastases were highly concordant (OR 8.6 and 16.7, respectively, each p <0.001). Overall FGFR protein expression levels did not differ between primary and metastatic lesions (p = 0.78). Up-regulated expression was recorded in 53 of 106 evaluable primary tumor spots and 56 matched metastases. Concordance of FGFR3 expression levels in 79 matched primary tumor and metastasis specimens was high (OR 8.45, p <0.001). In 15 and 12 patients expression was up-regulated in only metastasis and in only the primary tumor, respectively. Overall and recurrence-free survival was not related to FGFR3 expression.
    Conclusions: FGFR3 expression in matched primary and metastasized bladder cancer specimens showed good but not absolute concordance. Thus, in most patients primary tumor FGFR3 status can guide the selection of FGFR targeted therapy.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Prospective Studies ; Receptor, Fibroblast Growth Factor, Type 3/biosynthesis ; Urinary Bladder Neoplasms/metabolism ; Urinary Bladder Neoplasms/pathology
    Chemical Substances Receptor, Fibroblast Growth Factor, Type 3 (EC 2.7.10.1)
    Language English
    Publishing date 2015-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3176-8
    ISSN 1527-3792 ; 0022-5347
    ISSN (online) 1527-3792
    ISSN 0022-5347
    DOI 10.1016/j.juro.2014.06.026
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    Zs.MO 331: Show issues

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  5. Article ; Online: Determination of the consequences of VHL mutations on VHL transcripts in renal cell carcinoma.

    Taylor, Claire / Craven, Rachel A / Harnden, Patricia / Selby, Peter J / Banks, Rosamonde E

    International journal of oncology

    2012  Volume 41, Issue 4, Page(s) 1229–1240

    Abstract: Genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumour suppressor gene are common in sporadic conventional (clear cell) renal cell carcinoma (ccRCC). The effects on VHL expression are unknown but increased understanding may be relevant ... ...

    Abstract Genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumour suppressor gene are common in sporadic conventional (clear cell) renal cell carcinoma (ccRCC). The effects on VHL expression are unknown but increased understanding may be relevant clinically, either in terms of prognosis or in therapy selection. We have examined the expression of VHL mutant RNA in 84 ccRCC tumours previously screened for mutations in genomic DNA, 56 of which contained 52 unique mutations or polymorphisms. Based on the predicted change to the primary amino acid sequence, 24 of the mutations were missense, 11 resulted in frameshifts with premature truncation, 9 resulted in immediate truncation at the site of the mutation and 2 were frameshifts which extended the reading frame beyond the normal stop codon. Nine tumours had intronic variants, including substitution of invariant residues at splice sites, deletion of nucleotides spanning the exon-intron junction, an intronic variant of unknown function and the polymorphism c.463+43A>G. Four variants were identified which were present in genomic DNA but not in mRNA. Three of these, all encoding apparent missense changes to the primary amino acid sequence, were located close to the ends of exons, reduced the strength of the splice site and function as null rather than missense variants. One nonsense variant was not detectable in mRNA but all other mutations resulting in premature truncation codons (PTCs) were, suggesting truncating VHL mutations may potentially generate truncated VHL protein. An intronic variant, c.341‑11T>A, previously regarded as of unknown function, is associated with an increased level of skipping of exon 2 and may, therefore, reduce production of pVHL. Our data show that the biological consequences of VHL mutations are not necessarily predictable from the sequence change of the mutation and that for the majority of VHL mutations, the potential for the generation of mutant protein exists.
    MeSH term(s) Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/pathology ; DNA Methylation ; Exons/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Introns/genetics ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology ; Mutation/genetics ; Transcription, Genetic ; Von Hippel-Lindau Tumor Suppressor Protein/genetics
    Chemical Substances Von Hippel-Lindau Tumor Suppressor Protein (EC 2.3.2.27) ; VHL protein, human (EC 6.3.2.-)
    Language English
    Publishing date 2012-07-20
    Publishing country Greece
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1154403-x
    ISSN 1791-2423 ; 1019-6439
    ISSN (online) 1791-2423
    ISSN 1019-6439
    DOI 10.3892/ijo.2012.1561
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    Zs.A 3690: Show issues Location:
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  6. Article ; Online: Development and validation of a novel protein extraction methodology for quantitation of protein expression in formalin-fixed paraffin-embedded tissues using western blotting.

    Nirmalan, Niroshini J / Harnden, Patricia / Selby, Peter J / Banks, Rosamonde E

    The Journal of pathology

    2009  Volume 217, Issue 4, Page(s) 497–506

    Abstract: The development of efficient formaldehyde cross-link reversal strategies will make the vast diagnostic tissue archives of pathology departments amenable to prospective and retrospective translational research, particularly in biomarker-driven proteomic ... ...

    Abstract The development of efficient formaldehyde cross-link reversal strategies will make the vast diagnostic tissue archives of pathology departments amenable to prospective and retrospective translational research, particularly in biomarker-driven proteomic investigations. Heat-induced antigen retrieval strategies (HIARs) have achieved varying degrees of cross-link reversal, potentially enabling archival tissue usage for proteomic applications outside its current remit of immunohistochemistry (IHC). While most successes achieved so far have been based on retrieving tryptic peptide fragments using shot-gun proteomic approaches, attempts at extracting full-length, non-degraded, immunoreactive proteins from archival tissue have proved challenging. We have developed a novel heat-induced antigen retrieval strategy using SDS-containing Laemmli buffer for efficient intact protein recovery from formalin-fixed tissues for subsequent analysis by western blotting. Protocol optimization and comparison of extraction efficacies with frozen tissues and current leader methodology is presented. Quantitative validation of methodology was carried out in a cohort of matched tumour/normal, frozen/FFPE renal tissue samples from 10 patients, probed by western blotting for a selected panel of seven proteins known to be differentially expressed in renal cancer. Our data show that the protocol enables efficient extraction of non-degraded, full-length, immunoreactive protein, with tumour versus normal differential expression profiles for a majority of the panel of proteins tested being comparable to matched frozen tissue controls (rank correlation, r = 0.7292, p < 1.825e-09). However, the variability observed in extraction efficacies for some membrane proteins emphasizes the need for cautious interpretation of quantitative data from this subset of proteins. The method provides a viable, cost-effective quantitative option for the validation of potential biomarker panels through a range of clinical samples from existing diagnostic archives, provided that validation of the method is first carried out for the specific proteins under study.
    MeSH term(s) Actins/analysis ; Antibodies, Monoclonal ; Biomarkers/analysis ; Blotting, Western/methods ; Carcinoma, Renal Cell/chemistry ; Electrophoresis, Polyacrylamide Gel/methods ; Humans ; Kidney Neoplasms/chemistry ; Mass Spectrometry ; Membrane Proteins/isolation & purification ; Paraffin Embedding ; Proteins/isolation & purification ; Proteomics ; Reproducibility of Results ; Tissue Fixation
    Chemical Substances Actins ; Antibodies, Monoclonal ; Biomarkers ; Membrane Proteins ; Proteins
    Language English
    Publishing date 2009-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Validation Studies
    ZDB-ID 3119-7
    ISSN 1096-9896 ; 0022-3417
    ISSN (online) 1096-9896
    ISSN 0022-3417
    DOI 10.1002/path.2504
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  7. Article ; Online: Mining the archival formalin-fixed paraffin-embedded tissue proteome: opportunities and challenges.

    Nirmalan, Niroshini J / Harnden, Patricia / Selby, Peter J / Banks, Rosamonde E

    Molecular bioSystems

    2008  Volume 4, Issue 7, Page(s) 712–720

    Abstract: The significant potential of tissue-based proteomic biomarker studies can be restricted by difficulties in accessing samples in optimal fresh-frozen form. While archival formalin-fixed tissue collections with attached clinical and outcome data represent ... ...

    Abstract The significant potential of tissue-based proteomic biomarker studies can be restricted by difficulties in accessing samples in optimal fresh-frozen form. While archival formalin-fixed tissue collections with attached clinical and outcome data represent a valuable alternate resource, the use of formalin as a fixative which induces protein cross-linking, has generally been assumed to render them unsuitable for proteomic studies. However, this view has been challenged recently with the publication of several papers accomplishing variable degrees of heat-induced reversal of cross-links. Although still in its infancy and requiring the quantitative optimisation of several critical parameters, formalin-fixed tissue proteomics holds promise as a powerful tool for biomarker-driven translational research. Here, we critically review the current status of research in the field, highlighting challenges which need to be addressed for robust quantitative application of protocols to ensure confident high impact inferences can be made.
    MeSH term(s) Animals ; Fixatives/chemistry ; Formaldehyde/chemistry ; Humans ; Mass Spectrometry ; Paraffin Embedding ; Proteome/analysis ; Proteomics/methods ; Tissue Fixation
    Chemical Substances Fixatives ; Proteome ; Formaldehyde (1HG84L3525)
    Language English
    Publishing date 2008-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2188635-0
    ISSN 1742-2051 ; 1742-206X
    ISSN (online) 1742-2051
    ISSN 1742-206X
    DOI 10.1039/b800098k
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  8. Article ; Online: Metastatic castrate-resistant prostate cancer with a late, complete and durable response to docetaxel chemotherapy: a case report.

    Daverede, Luis / Ralph, Christy / Jagdev, Satinder P / Trigonis, Ioannis / Trainor, Sebastian / Harnden, Patricia / Weston, Michael / Paul, Alan / Vasudev, Naveen S

    Journal of medical case reports

    2014  Volume 8, Page(s) 122

    Abstract: Introduction: Although treatment options for men with metastatic castrate-resistant prostate cancer have improved in recent years, the outlook for patients remains poor, with overall survival in the region of 2 years. Response rates with chemotherapy ... ...

    Abstract Introduction: Although treatment options for men with metastatic castrate-resistant prostate cancer have improved in recent years, the outlook for patients remains poor, with overall survival in the region of 2 years. Response rates with chemotherapy are modest and disease progression is usually observed within months of stopping treatment.
    Case presentation: We present a case of a 72-year-old White man of British origin with metastatic castrate-resistant prostate cancer with bulky lymphadenopathy and a serum prostate-specific antigen of 295 μg/L. He received treatment with docetaxel chemotherapy plus prednisolone, but received just 3 cycles before treatment was stopped due to toxicity and lack of response (prostate-specific antigen was 276 μg/L 4 weeks after the last dose and there was a confirmed stable appearance on computed tomography scan). Unexpectedly, at follow-up 4 months later, the patient was clinically better; his prostate-specific antigen had dramatically improved to 4.1 μg/L and a re-staging computed tomography scan revealed complete resolution of his bulky lymphadenopathy. At the time, he was receiving a luteinising hormone-releasing hormone analogue but no other disease-modulating treatment. He remains well and asymptomatic, with his most recent serum prostate-specific antigen measuring 0.14 μg/L, 18 months after last receiving chemotherapy.
    Conclusion: We report a case of complete and durable regression of metastatic castrate-resistant prostate cancer following palliative chemotherapy which, to the best of our knowledge, has not previously been reported in the literature.
    MeSH term(s) Adenocarcinoma/drug therapy ; Adenocarcinoma/pathology ; Aged ; Androgen Antagonists/therapeutic use ; Anilides/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Docetaxel ; Goserelin/therapeutic use ; Humans ; Lymphatic Metastasis ; Male ; Nitriles/therapeutic use ; Prostate/pathology ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/pathology ; Taxoids/therapeutic use ; Tosyl Compounds/therapeutic use ; Treatment Failure ; Treatment Outcome
    Chemical Substances Androgen Antagonists ; Anilides ; Antineoplastic Agents ; Antineoplastic Agents, Hormonal ; Nitriles ; Taxoids ; Tosyl Compounds ; Goserelin (0F65R8P09N) ; Docetaxel (15H5577CQD) ; bicalutamide (A0Z3NAU9DP)
    Language English
    Publishing date 2014-04-09
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2269805-X
    ISSN 1752-1947 ; 1752-1947
    ISSN (online) 1752-1947
    ISSN 1752-1947
    DOI 10.1186/1752-1947-8-122
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  9. Article ; Online: Evaluation of the use of digital images for a national prostate core external quality assurance scheme.

    Harnden, Patricia / Coleman, Derek / Moss, Sue / Kodikara, Sandhya / Griffin, Nick R / Melia, Jane

    Histopathology

    2011  Volume 59, Issue 4, Page(s) 703–709

    Abstract: Aims: To evaluate the use of virtual images as an alternative to glass slides to expand the number of participants in the External Quality Assurance Scheme for prostatic biopsies.: Methods and results: Benign and neoplastic cases, previously ... ...

    Abstract Aims: To evaluate the use of virtual images as an alternative to glass slides to expand the number of participants in the External Quality Assurance Scheme for prostatic biopsies.
    Methods and results: Benign and neoplastic cases, previously circulated as glass slides, were selected to include cases that had demonstrated a high level of agreement (n = 10) and a lesser degree of agreement (n = 10). Whole slide virtual images were circulated to 68 pathologists; 51 responses were returned. The levels of agreement for the primary diagnosis and for Gleason grading of cancers were analysed using kappa statistics. Responses for glass slides versus images were compared for the 24 pathologists for whom data were available. Levels of agreement for diagnostic categories using virtual slides were moderate to substantial, comparable to those found using glass slides. The level of agreement for Gleason grades 8-10 was substantial, but for lower grades was fair or moderate, poorer than for the glass slide circulation.
    Conclusions: Circulation of virtual images of biopsy material is a suitable alternative to glass slide-based schemes for the evaluation of diagnostic consistency. The majority of participants agreed that the ability to evaluate limited diagnostic material outweighed the disadvantages of a virtual system.
    MeSH term(s) Biopsy ; Diagnostic Imaging/methods ; Humans ; Image Interpretation, Computer-Assisted ; Male ; Microscopy ; Observer Variation ; Pathology, Clinical/standards ; Prostate/pathology ; Prostatic Neoplasms/diagnosis ; Quality Assurance, Health Care/methods ; Quality Assurance, Health Care/standards ; Telepathology/methods ; User-Computer Interface
    Language English
    Publishing date 2011-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/j.1365-2559.2011.03987.x
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  10. Article ; Online: A practical application of analysing weighted kappa for panels of experts and EQA schemes in pathology.

    Wright, Karen C / Harnden, Patricia / Moss, Sue / Berney, Dan M / Melia, Jane

    Journal of clinical pathology

    2011  Volume 64, Issue 3, Page(s) 257–260

    Abstract: Background: Kappa statistics are frequently used to analyse observer agreement for panels of experts and External Quality Assurance (EQA) schemes and generally treat all disagreements as total disagreement. However, the differences between ordered ... ...

    Abstract Background: Kappa statistics are frequently used to analyse observer agreement for panels of experts and External Quality Assurance (EQA) schemes and generally treat all disagreements as total disagreement. However, the differences between ordered categories may not be of equal importance (eg, the difference between grades 1 vs 2 compared with 1 vs 3). Weighted kappa can be used to adjust for this when comparing a small number of readers, but this has not as yet been applied to the large number of readers typical of a national EQA scheme.
    Aim: To develop and validate a method for applying weighted kappa to a large number of readers within the context of a real dataset: the UK National Urological Pathology EQA Scheme for prostatic biopsies.
    Methods: Data on Gleason grade recorded by 19 expert readers were extracted from the fixed text responses of 20 cancer cases from four circulations of the EQA scheme. Composite kappa, currently used to compute an unweighted kappa for large numbers of readers, was compared with the mean kappa for all pairwise combinations of readers. Weighted kappa generalised for multiple readers was compared with the newly developed 'pairwise-weighted' kappa.
    Results: For unweighted analyses, the median increase from composite to pairwise kappa was 0.006 (range -0.005 to +0.052). The difference between the pairwise-weighted kappa and generalised weighted kappa for multiple readers never exceeded ±0.01.
    Conclusion: Pairwise-weighted kappa is a suitable and highly accurate approximation to weighted kappa for multiple readers.
    MeSH term(s) Biopsy/standards ; Data Interpretation, Statistical ; Humans ; Male ; Observer Variation ; Pathology, Clinical/standards ; Prostatic Neoplasms/pathology ; Quality Assurance, Health Care ; United Kingdom
    Language English
    Publishing date 2011-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Validation Studies
    ZDB-ID 80261-x
    ISSN 1472-4146 ; 0021-9746
    ISSN (online) 1472-4146
    ISSN 0021-9746
    DOI 10.1136/jcp.2010.086330
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