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  • 1
    Digitale Medien
    Digitale Medien
    Suite 500, 5th Floor, 238 Main Street, Cambridge Massachusetts 02142, USA : Blackwell Science Inc.
    International journal of gynecological cancer 6 (1996), S. 0 
    ISSN: 1525-1438
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Earlier studies have shown the strong prognostic value of the mitotic activity index (MAI), volume percent of epithelium (VPE), mean nuclear area (MNA) and the standard deviation of the nuclear area (SDNA) in early and advanced ovarian cancer. In one study of Danish patients however, these features were not significant and methodological causes were excluded as a cause of this. Therefore, we have re-evaluated these features in another group of 112 Danish patients with FIGO stage III ovarian cancer who were treated with debulking surgery followed by cisplatin combination chemotherapy. Thirty-seven patients (33%) survived. In survival analysis residual disease status, performance status, peritoneal carcinomatosis, histologic grade, age and the presence or absence of ascites had significant influence on the eventual clinical outcome. Of the quantitative pathologic features the MAI, MNA, SDNA were correlated with grade, but had stronger prognostic value than grade. Residual disease status, performance status at diagnosis, peritoneal carcinomatosis, the MNA and the SDNA were the best single prognostic variables (P 〈 0.00001). With multivariate analysis residual disease status, MNA and age had independent additional value (grade was not selected once these more significant features were included). With this combination (called F3MS) four prognostically important groups could be distinguished (MC = 61.7, P 〈 0.00001). Survival in the most favourable F3MS group (n = 28) was 71% (median survival time 84 months), while in the worst group (n = 29) none of the patients survived and the median survival time in this group was only 13 months (Relative Risks (RR) = 3.50). It is concluded that morphometric variables have important value in predicting prognosis in patients with FIGO stage III ovarian cancer and add to the classical prognostic factors of residual disease status and age.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    238 Main Street, Cambridge, MA 02142, USA : Blackwell Scientific Publications
    International journal of gynecological cancer 4 (1994), S. 0 
    ISSN: 1525-1438
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Earlier studies have shown that morphometric analysis of nuclear size and shape features and stereologic analysis of gland architecture in endometrial hyperplasia are useful to predict the risk of progression to cancer. A multivariate discriminatory D-score using these features has a higher sensitivity than qualitative microscopic characteristics (nuclear atypicality and glandular complexity) when an appropriate threshold is chosen. In the present study, the (additional) prognostic value of morphometric features related to the arrangement of nuclei in glands (distance of nuclear centroids to basal membrane, angle of longest nuclear axis with basal membrane) and DNA-ploidy (determined by flow cytometry) has been analyzed in 39 cases of endometrial hyperplasia, seven (18%) of which have progressed to cancer. Variation in stratification of nuclei has prognostic value, in contrast to DNA-ploidy. Multivariate analysis selects the outer surface density of the glands, mean distance, volume percentage of lumen and the coefficient of variation of nuclear axes as having separate and additional value. A multivariate rule called HYPER-score results from these features. With this score a high-risk (score value 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:1048891X:IJG04050289:ges" location="ges.gif"/〉0.20, nine cases, 78% progressed) and a low-risk group (score value 〈0.20, 30 cases, none progressed) can be discerned. The prognostic value, sensitivity and specificity of the hyper-score greatly exceeds that of any of the previously described prognostic factors in endometrial hyperplasias. An additional clinical advantage is that with the HYPER-score two groups (instead of four groups as with Kurman’s method(1)) with a high sensitivity and specificity can be discerned. The morphometric and stereologic features agree well with the usual qualitative predictors but have much stronger prognostic value.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1525-1438
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Safety and feasibility of tumor targeting with radiolabeled monoclonal antibodies was studied in 28 patients suspected of having ovarian carcinoma, after i.v. administration of 1 mg F(ab′)2 fragments of the murine monoclonal antibody OV-TL 3, labeled with 150 MBq Indium-111. There were no adverse reactions, hematological and biochemical serum parameters were stable. In one patient a (subclinical) HAMA-response was found. Plasma clearance of the immunoconjugate was biphasic with half lives of t½}α = 1.4±0.8 h and t½}β = 25.1±3.7 h, resulting in an optimal time period for immunoscintigraphy at 24–48 h after administration. In 20 patients, undergoing extensive explorative surgery, a total of 271 samples of tumorous and normal tissues were analyzed for radiolabel uptake and tumor presence. The mean uptake in tumor deposits was 5.6 times (range 2.2–19.3) as high as the uptake in normal tissues (fat, peritoneum, muscle, skin). The diagnostic accuracy of immunosctigraphy was compared with that obtained with computer tomography, magnetic resonance imaging, ultrasonography and physical examination. While pelvic localizations were equally well detected by all methods, 48% of the abdominally located tumor deposits were correctly diagnosed by immunoscintigraphy, with only 12% detected by ultrasonography, 8% by CT-scanning and physical examination, and 6% by MRI. Immunoscintigraphy has potential as a diagnostic tool in ovarian cancer patients and biolocalization results justify further research into the therapeutic application of labeled monoclonal antibodies.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Suite 500, 5th Floor, 238 Main Street, Cambridge, Massachusetts 02142, USA : Blackwell Science Inc.
    International journal of gynecological cancer 5 (1995), S. 0 
    ISSN: 1525-1438
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Previous studies have shown DNA cytometric, morphometric and stereologic features to be strong prognosticators in advanced ovarian cancer. However, in one Danish study a new stereologic parameter, the volume-weighted mean nuclear volume ( νv), was not of prognostic significance. In that study, sampling was performed in the whole tumor section, contrary to that in other studies where measurements were performed in the worst differentiated area (the measurement area). The aim of the present investigation was, therefore, to confirm or reject the hypothesis that random estimates of nuclear {ovbar|ν}v over the whole tumor, rather than in the measurement area, are the cause for the lack of prognostic value in the Danish patients. Additionally, the mitotic activity index (MAI), volume percentage of epithelium (VPE), mean nuclear area (MNA) and standard deviation of the nuclear area (SDNA), which have proved to be of strong prognostic significance in advanced ovarian cancer, were assessed in the measurement area. The MAI, VPE, MNA, SDNA and nuclear {ovbar|ν}v were well reproducible, but prognostically not significant. This study thus excludes differences in microscopic sampling as an explanation for the contrasting findings in the Danish study and other ones. Possible remaining explanations are: (i) differences in sampling at the macroscopic level; (ii) fixation differences; (iii) patient selection bias; and (iv) geographic differences in the degree of malignancy of advanced ovarian cancer in Denmark and the Netherlands. As to the latter, in comparison with two Dutch studies the Danish ovarian cancers in this series had residual disease 〈2 cm (33% vs 50%) less often, were less often well differentiated (4% vs 19%), and less often had favorable morphometric characteristics (6% vs 15%). Further studies are required to analyze whether other Danish patient groups with advanced ovarian cancers differ from the Dutch.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Suite 500, 5th Floor, 238 Main Street, Cambridge, Massachusetts 02142, USA : Blackwell Science Ins.
    International journal of gynecological cancer 5 (1995), S. 0 
    ISSN: 1525-1438
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: In order to analyse the reproducibility and prognostic value of histologic typing and different methods of histologic grading, 102 hematoxylin and eosin stained slides of primary FIGO stage I ovarian cancers of the common epithelial types were evaluated. Patients were treated by surgery only. Histologic typing was done using the FIGO criteria and overall total agreement was 61%. Survival was not statistically significant (P-value range: 0.31–0.66). For grading, three different methods were used: (a) the ‘intuitive’ method; (b) the FIGO method; and (c) the so-called Pathology Research and Practice (PRP) method, which is based on invasion, architecture and nuclear atypia. The best intra- and interobserver results were obtained with the PRP criteria (interobserver agreement rate: 84.3%, ϰ 0.67; intraobserver agreement rate: 87.3%, K 0.76). Univariate survival analyses showed significant differences between grades for all methods and observers. Results of the PRP method were clearly better than for the FIGO method (PRP, Mantel-Cox range 6.70–24.52,P-value range 0.07 − 〈 0.0001; FIGO, Mantel-Cox range 5.31–6.77,P-value range 0.07–0.034). The 5-year survival per grade showed considerable variation within and between the observers, and was higher with higher grade. We conclude that the assessment of histologic type was reproducible but prognostically not significant in this set of FIGO stage I ovarian cancer patients. The intra- and interobserver reproducibility of the same grading method was fair to good, and showed highly significant results for survival from the PRP method. However, application of different grading methods could result in considerable prognostic variations for the ‘same’ grades.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    238 Main Street, Cambridge, Massachusetts 02142, USA : Blackwell Scientific Publications
    International journal of gynecological cancer 4 (1994), S. 0 
    ISSN: 1525-1438
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: The prognostic value of morphometric and DNA flow cytometric features were studied and compared with FIGO stage, preoperative tumor load, residual disease status, Karnofsky index and classic pathologic features such as Broders’ grade and histologic type in 58 FIGO stage III and IV adequately debulked ovarian patients with long-term follow-up. The mitotic activity index, volume percentage of epithelium, and mean and SD of nuclear area were assessed by interactive morphometry, and tumor material was routinely processed for DNA flow cytometric assessment of DNA ploidy and S-phase fraction. Survival analysis (Kaplan-Meier curves, Mantel-Cox test), revealed FIGO stage (P = 0.013) and the mean and SD of nuclear area to be significant prognosticators (P = 0.027 and P = 0.012, respectively). In multivariate survival analysis (Cox model), a multivariate combination of FIGO stage, preoperative tumor load and mean nuclear area was the best prognostic combination of features (P = 0.0034). These results confirm the findings of previous studies. We conclude that, in accord with previous studies, morphometric features are good predictors of survival after cisplatin treatment in advanced ovarian cancer, especially in combination with FIGO stage and preoperative tumor load.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Suite 500, 5th Floor, 238 Main Street, Cambridge, Massachussets 02142, USA : Blackwell Science Inc.
    International journal of gynecological cancer 6 (1996), S. 0 
    ISSN: 1525-1438
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: In a previous investigation, a group of Danish FIGO III and IV ovarian cancer patients from Aarhus were found to have more aggressive tumor characteristics compared with Dutch patients, concerning histologic grade, morphometric features and residual disease status. The aim of the present investigation was to investigate possible geographic differences in clinicopathologic and quantitative prognostic features in a large group of Dutch and Danish patients only with FIGO III ovarian carcinoma, from Copenhagen and to compare the survival of these two groups. One hundred and sixty-nine patients were included in the current investigation, all were treated with debulking surgery followed by cisplatin combination chemotherapy. Dutch patients (42% survived, median survival time 48 months) had a significantly better survival than the Danish patients (33% survived, median survival time 27 months) (Mantel-Cox (MC) = 6.0, P = 0.01). In the subgroup with residual disease larger than 2 cm, survival differences were even more striking: survival was 32% in Dutch patients (median survival time 24 months) and 15% in Danish patients (median survival time, 16 months). Logistic regression analysis revealed that the geographic survival difference was associated with differences in the morphometric feature mean nuclear area (MNA). The MNA was significantly larger in the Danish ovarian tumors (78 µm2 vs 63 µm2). With a cut-off point for MNA of 75 µm2, survival was similar for the Dutch and Danish patients with values below and also for those above that value, but Danish patients had many more values above 75 µm2. Therefore, the MNA is a useful prognosticator in patients with FIGO III ovarian cancer treated with cisplatin combination chemotherapy, especially since this variable is not susceptible to geographic differences. The reason for the difference in MNA, and consequently worse survival in Danish patients, remains to be elucidated.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Suite 500, 5th Floor, 238 Main Street, Cambridge, Massachussetts 02142, USA : Blackwell Science Inc.
    International journal of gynecological cancer 5 (1995), S. 0 
    ISSN: 1525-1438
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: In FIGO stage I endometrial cancer patients, histologic type and grade are correlated with prognosis and used for therapeutic decision making. However, assessment of these histologic features is subjective, and the results are not always perfectly reproducible. Contrarily, previous studies have shown that DNA-ploidy and morphometric features are highly reproducible and have a strong prognostic value in these cancers. Multivariate analysis has demonstrated that a combination of mean shortest nuclear axis (MSNA), DNA-ploidy and depth of myometrial invasion (the so-called ECPI-1 score) overshadowed the value of all other features investigated. The present study was set up to evaluate further and compare the prognostic power of the ECPI-1 score in 77 FIGO I patients with long follow-up (10–15 years). Grade (revised), invasion depth, MSNA and ploidy were all highly significant. However, the ECPI-1 score (with exactly the same threshold as in the previous study, 0.87) greatly exceeded the prognostic value of these single features. Only two (3%) of the 64 patients with ECPI-1 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:1048891X:IJG05020112:les" location="les.gif"/〉0.87 died (at 14 and 62 months), in contrast to 11 (84.6%) of the 13 cases with ECPI-1〉 0.87 (10 died within 42 months) (P 〈 0.0001, Mantel-Cox value = 51.1). These results confirm the prognostic strength of the ECPI-1 score in stage I endometrial carcinoma.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Histopathology 21 (1992), S. 0 
    ISSN: 1365-2559
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: The intra-patient variations of some clinically relevant quantifiable features, between axillary lymph node metastases were evaluated in 44 breast cancer patients. In all lymph node metastases detected (range 2-33 per patient), the mitotic figures were counted, the volume percentage epithelium was assessed and the mean nuclear area was measured. The intra-patient variation for each quantifiable feature was expressed by the coefficient of variation (CV). Since the measurement techniques used introduce a certain, well known variation themselves because of sampling and measurement errors, the CVs found had to be greater than methodological tolerance limits (established in previous studies) to be interpreted as indicating biological variation.The CVs exceeded the methodological tolerance limits in 86% of the cases for the mitotic count, in 48% of the cases for the volume percentage epithelium, and in 47% of the cases for the mean nuclear area. This indicated that in these cases, the variation found in the quantifiable features could not be explained by sampling or measurement errors and should be regarded as real biological variation. Furthermore, the variation in the quantifiable features studied showed a significant positive correlation with the number of lymph node metastases.Thus, there may be considerable intra-patient variation in quantifiable features between axillary lymph node metastases in breast cancer. This may indicate that these lymph node metastases originate independently from different clones within the primary tumour, that they are independently formed in different stages of tumour development, or that they, as an expression of intrinsic tumour heterogeneity, may develop in different directions from the start.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1365-2559
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Histological typing of invasive breast cancer according to the World Health Organisation criteria is prognostically relevant, because some histological subtypes have a markedly better prognosis. However, reproducibility of histological typing is not high because of the absence of strict typing criteria, variations in the application of the typing criteria and the usually limited illustration of the relevant criteria. The aim of this study was to develop an expert system based on highly structured histological typing criteria, integrated with high-quality microscope images to illustrate the typing criteria. This system should be useful as a decision support system in the diagnosis of breast cancers and should increase the reproducibility of histological typing. Criteria for typing were extracted from textbooks and, based on experience, these criteria were structured and implemented in the Relation Oriented Inference System (ROIS), in which information can be structured by defining relations. Illustrative black and white images were digitized and integrated into the shell. The performance of the resulting decision support system was evaluated by a group of six pathologists using a set of slides covering the spectrum of the most frequently occurring histological types of invasive breast cancer. The pathologists first assessed histological type according to standard morphological procedures. The cases were then reassessed with the decision support system available for consultation. The use of the decision support system appeared to influence the previously assessed histological type in about half of the cases. Using the decision support system, histological typing was more uniform and more in accord with a ‘gold standard’ set by two experts. The integrated decision support system/image archive for histological typing of breast cancer seems to be a useful instrument in daily diagnostic breast histopathology as well as being a potential teaching tool. It may contribute to a more reproducible and prognostically relevant histological typing of breast cancer.
    Materialart: Digitale Medien
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