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V Dimmer

Publications and source records attributed to V Dimmer.

At least 19 recordsLinked to original sources

[Tonsillectomy by CO@ laser microsurgery--an analysis of clinical and morphological data].

BACKGROUND: Tonsillectomy by CO(2) laser microsurgery is an almost bloodless procedure that has developed to an alternative to traditional dissection tonsillectomy during recent years. It has been suggested that the laser technique more precise than the conventional one, however, attempts to investigate this morphologically have not yet been undertaken. In addition, there is a need for large clinical studies to compare the postoperative bleeding risk of both procedures. METHODS: The charts of 617 patients who underwent routine tonsillectomy between 1995 and 1998 at the ENT department of Darmstadt Hospital, were retrospectively investigated with regard to postoperative bleeding events. A total of 467 patients were treated by the conventional technique and 150 by CO(2) laser microsurgery (continuous mode, 5 W). Moreover, 2 mm serial sections of tonsils of 56 consecutive patients treated in 1999 (31 conventional and 25 laser tonsillectomies) were used to determine peritonsillar (Vp) and tonsillar tissue volumes (Vt). RESULTS: The postoperative bleeding risk following laser tonsillectomy differed slightly from that following the conventional technique (12.0% vs 14.6%; P=0.499; Fisher's exact test). However, the incidence of severe bleeding events requiring revision in general anesthesia was significantly reduced (0.7% vs 4.9%; P=0.015; Fisher's exact test). Tonsillar specimens that were removed by laser surgery contained significantly less peritonsillar tissue than those from conventional procedures (Vp/Vt 5.1%+/-0.6% vs 10.8%+/-1.1%; P below 0.001; Mann-Whitney U-test). CONCLUSION: CO(2) laser microsurgery improves the precision of tonsillectomy and provides a maximum protection for the peritonsillar tissue. The incidence of severe bleeding events is markedly reduced. Laser tonsillectomy is therefore recommended for patients with clotting disorders or those requiring a particularly exact preparation technique.

Adolescent↗

DNA ploidy and chromosomal imbalances in invasive ductal breast cancer. A comparative study of DNA image cytometry and comparative genomic hybridization (CGH).

Chromosomal imbalances were analyzed in 62 breast cancers with different DNA ploidy by CGH. The results of DNA image cytometry and CGH are consistent with peridiploid and aneuploid cases. The peritetraploid tumors harbored a high number of chromosomal imbalances, as a hint for an unfavorable prognosis. The quantitative analysis of imbalances highlighted the role of different physical constituents of the chromosome, and of chromosomal losses in different DNA ploidy groups. The peritetraploid and aneuploid tumors differed from the peridiploid tumors in losses at 8p and 18q. The peritetraploid cancers exhibited more gains at 8q, the aneuploid tumors more losses at 17p than their peridiploid counterparts. The aneuploid cases differed from the peritetraploid tumors in a higher number of losses at 11q and 14q. Combinations of imbalances provide further insights into the genetic background of DNA ploidy. Hypotheses for the progression from peridiploid to nondiploid breast cancers are given.

Breast Neoplasms↗

Loss of caveolin expression in type I pneumocytes as an indicator of subcellular alterations during lung fibrogenesis.

Caveolin is a major structural protein of caveolae, also known as plasmalemmal vesicles, which are particularly abundant in type I pneumocytes and capillary endothelial cells of lung parenchyma. Here we demonstrate that caveolin expression in the alveolar epithelium of rats and mini pigs is strikingly downregulated after irradiation-induced lung injury. Indirect immunoperoxidase staining with polyclonal anti-caveolin antibodies, confirmed by double fluorescence studies with type I cell-specific monoclonal anti-cytokeratin antibodies or lectins, revealed a dramatic loss of caveolin immunoreactivity in type I pneumocytes. In contrast, caveolin expression increased in endothelial cells. Immunoblotting of lung homogenates from normal and irradiated rats using specific anti-caveolin antibodies confirmed the presence of caveolin in normal tissue and its marked decrease of expression in fibrotic tissue. The loss of caveolin as an important structural protein of caveolae in alveolar epithelial cells may be an early indicator of serious type I cell injury during fibrogenesis. The increase of caveolin immunoreactivity in endothelia of blood vessels may indicate that different types of caveolae and/or different regulatory mechanisms of caveolin expression exist.

Animals↗

Morphological heterogeneity of p53 positive and p53 negative nuclei in breast cancers stratified by clinicopathological variables.

The study was aimed to detect differences in nuclear morphology between nuclear populations as well as between tumours with different p53 expression in breast cancers with different clinicopathological features, which also reflect the stage of tumour progression. The p53 immunohistochemistry was performed on paraffin sections from 88 tumour samples. After the cells had been localised by means of an image cytometry workstation and their immunostaining had been categorised visually, the sections were destained and stained by the Feulgen protocol. The nuclei were relocated and measured cytometrically by the workstation. There were significant differences in the nuclear features between tumours as well as between nuclear populations with different p53 expression in the most subgroups. The variability of nuclear shape in tumour groups, classified by the tumour size or the lymph node status, increase with the p53 immunoreactive score, whereas in tumours grouped by the Bloom-Richardson grade features of the chromatin distribution were different between the p53 staining categories. The nuclear subpopulations showed differences in the amount and distribution of chromatin in most subgroups. The results demonstrate the relationship between the nuclear morphology and the p53 expression in different stages of breast cancers. The p53 status is an important factor of the biological behaviour but not the only one.

Breast Neoplasms↗

Correlation between p53 status, DNA ploidy, proliferation rate and nuclear morphology in breast cancer. An image cytometric study.

The study was designed to detect differences in the nuclear morphology of tumours and tumour cell populations with different p53 expression in correlation with DNA ploidy and proliferation rate. The paraffin sections from routinely processed samples of 88 breast cancers were immunostained with the monoclonal p53-antibody DO-1. After localization and evaluation with a scoring system the sections were destained and stained by the Feulgen method. The nuclei were relocated automatically and measured by means of the image cytometry workstation. Significant differences between the tumours and tumour cell populations with different p53 expression were found in the euploid tumours as well as in the aneuploid tumours and in the breast cancers with a high proliferation rate. The breast cancers with a low immunoreactive score (IRS 1-4) differ from the negative cancers as well as from the cancers with a higher immunoreactive score (IRS 5-12). Evaluating the nuclear populations of the p53 positive cancers, there were differences in the features of the chromatin amount and distribution in the groups of the euploid breast cancers and in cancer with a high proliferation rate. In contrast, the nuclear populations of the aneuploid cancers did not show any differences in their nuclear morphology. The results showed the different impacts of the p53 expression, DNA ploidy and the proliferation rate on the nuclear morphology in breast cancer.

Adult↗

DNA histogram interpretation based on statistical approaches.

Image cytometric DNA measurements provide data which are most often interpreted as equivalent to the chromosomal ploidy although the chromosomal and the DNA ploidy are not identical. The common link between them is the cell cycle. Therefore, if destined for DNA ploidy interpretations, the DNA cytometry should be performed on a population-oriented stochastic basis. Using stochastic sampling the data can be interpreted by applying the rules of stochastic processes. A set of statistical methods is given that enables a DNA histogram to be interpreted objectively and without human interaction. These statistics analyse the precision and accuracy of the entire measurement process. They give in error probabilities for accepting a measurement as reliable, for recognition of stemlines, stemline aneuploidy, and for evaluating so-called rare events. Nearly 300 image cytometric DNA measurements from breast cancers and rat liver imprints examples have been selected to demonstrate the efficiency of the statistics in each step of interpreting DNA histograms.

Aneuploidy↗

Nuclear image analysis of p53-positive and -negative cells in breast carcinoma.

OBJECTIVE: To detect differences in nuclear morphology in breast carcinoma cells with different p53 expression. STUDY DESIGN: Immunohistochemical reactions were performed on paraffin sections from 88 breast cancers with the monoclonal antibody DO-1. By means of an image cytometry workstation, 500 nuclei were localized and categorized in an immunohistochemical staining scoring system in each case. After destaining and Feulgen staining, the nuclei were relocated and measured by means of the workstation. RESULTS: P53-positive nuclei showed greater irregularity of the chromatin pattern and stronger granularity of the chromatin. There were also differences in the chromatin texture and nuclear shape between tumors different in their p53 expression. The p53-negative nuclear population from the p53-positive tumors and the whole nuclear population of the p53-negative tumors were morphologically different, also. CONCLUSION: Nuclear image analysis of immunohistochemically characterized cells allows further insight into the relationship of structure and function in malignant tumor cells.

Adult↗

Nuclear image analysis of immunohistochemically stained cells in breast carcinomas.

Hitherto, the relationship between malignancy-associated morphological features in single tumour cells and the expression of markers indicating functional properties of these cells remained widely unknown. This study was aimed at describing differences in the size, shape and chromatin structure between tumour cells with different marker expression for progesterone receptors (PgR) and p53. Two series of breast cancers, consisting of 50 PgR-positive, and 39 p53-negative and 49 p53-positive mammary carcinomas, were investigated. The immunohistochemical staining was performed on paraffin sections using 3-amino-9-ethylcarbazole as the chromogenic substrate. By means of a cytometry workstation equipped with a computer-controlled motorised scanning stage, about 500 positive and negative tumour cells in each case were localised in the microscope and categorised by a scoring system for their staining intensity. After destaining, the tissue sections were Feulgen-stained. Then, all the tumour cells were relocated automatically and analysed by high resolution image cytometry. Among the numerous size, shape, and texture features used in the system, several variables of the nuclear contour and chromatin structure were found to be significantly different between the positive and negative tumour cell populations. Nuclei without PgR had more malignancy-associated morphological features than PgR-positive cells. Whereas p53-negative nuclei had a higher degree of regularity, their positive counterparts exhibited higher DNA ploidy values.

Biomarkers, Tumor↗

Distribution of von Willebrand factor in capillary endothelial cells of rat lungs with pulmonary fibrosis.

To determine the value of von Willebrand factor (vWF) antigen as a marker of endothelial injury in radiation-induced fibrosis of rat lungs, we studied endothelial immunoreactivity to antibodies against vWF using the indirect immunoperoxidase technique combined with morphometric analysis. Using immunoelectron microscopy of LR White embedded lung samples to detect vWF, immunogold-labelled Weibel Palade bodies were found in endothelial cells of capillary endothelium. The irradiated lungs showed a statistically significant elevation of vWF expression, ie, vWF positive endothelia per unit area, and a significant increase of vWF expression per unit of parenchyma as well. The results suggest that vWF antigen expression and the number of vWF positive structures is modulated under condition of injury in radiation-induced fibrosis.

Animals↗

Cellular sociology of proliferating tumor cells in invasive ductal breast cancer.

OBJECTIVE: The topology of proliferating cells in tissue sections of breast cancers was studied as the static expression of the cellular sociology of distinct subpopulations of tumor cells. With the terms neighborhood and connectivity, an attempt was made to describe the mutual interrelations of cycling tumor cells objectively in different prognostic subgroups of invasive ductal breast carcinomas. STUDY DESIGN: For these studies the spatial distribution of Ki-67 (Mib1)-positive tumor cells was investigated by means of Voronoi tesselation, minimum spanning tree techniques, cluster analysis and second-order stereology in a series of 80 breast tumors. Thirty-nine basic features were used for describing the topology of tumor cells with different degrees of Mib-1 reactivity. RESULTS: Multivariate analyses demonstrated different proliferation patterns associated with tumor size, nodal status, histopathologic grade, DNA ploidy and flow cytometric proliferation variables. CONCLUSION: Independent of the spatial organization of the tumor cells, their tissue pattern of proliferation activity correlated with the tumor properties.

Antigens, Nuclear↗

Expression of p53 and bcl-2 in correlation to clinicopathological parameters, hormone receptor status and DNA ploidy in breast cancers.

The expression of p53 and bcl-2 was immunohistochemically investigated in 61 formalin-fixed, paraffin-embedded invasive breast carcinomas. The study was aimed to elucidate the relationship between both markers and the correlation of p53 and bcl-2, respectively, to clinicopathological variables, to hormone receptor status and to DNA-ploidy. Twenty tumors showed a positive reaction with the monoclonal antibody DO-1 against p53 protein. Its immunohistochemical demonstration was significantly correlated with a tumor size larger than 2 cm, a low estrogen receptor status and DNA-aneuploidy. Bcl-2 was demonstrated in 51 breast cancers. Bcl-2 was preferably seen in low grade and hormone receptor positive tumors. We found a negative correlation between the immunoreactive scores of p53 and bcl-2, but in 17 carcinomas a coexpression of both proteins was seen. Cases with this coexpression did not differ significantly from the other tumors in clinicopathological parameters. In eight of these cases more than 10% of the cells were found to be positive for both markers. In four cases we could show many cells to exhibit both markers as it was assessed by an immunofluorescence double labeling technique.

Breast Neoplasms↗

Feasibility and limitations of a cytometric DNA ploidy analysis procedure in tissue sections.

To produce IOD histograms from tissue sections interpretable in terms of DNA ploidy, compromises between section thickness, nuclear volume and cellularity have to be found. In most cases, some kind of correction for capping effects will be inevitable. One of the correction procedures for that purpose was studied, i.e. that concerning the extent of errors which are necessarily introduced by assuming a distributional model of nuclei in the tissue slide. This procedure is mainly based on the assumptions of a spherical shape of the nuclei, of their homogeneous chromatin distribution, and of an equal distribution of the equatorial plane inside the tissue slide sectioned. Measurements on rat liver sections with a series of section thicknesses demonstrated that the correction procedure would lead to an exact position of the IOD peaks from the tetraploid nuclei on the ploidy axis. The width of the IOD peaks will not be diminished considerably as compared to uncorrected IOD histograms. Therefore, there are serious limitations to the procedure as compared to the DNA ploidy analysis on smears or imprints. If applied very critically in the case of tissue sections, the method may provide additional information about the DNA ploidy in those cases which lack a uniform tumour cell population or adequate material for smear preparations.

Animals↗

["Nucleolar organizer regions" as a factor for the prognosis of laryngeal cancer?].

The prognostic significance of silver-binding nucleolar organizer regions (AgNORs) was assessed in tissue sections of primary tumours taken from 30 patients with squamous cell carcinomas of the larynx. By means of semiautomated image analysis the AgNORs of 100 tumour cell nuclei were measured. Their number as well as their area were evaluated together with morphometrical features (obtained by automated image analysis) and histopathological and clinical data. Considering the mean number of AgNORs the multivariate discriminant analysis revealed significant differences between carcinomas of patients, who were alive of at least 3 years without local or distant recurrence and those, who had died of laryngeal cancer (p less than 0.03%). There was, however, no correlation between the AgNOR number and the DNA features. But, on the other hand, the DNA features, e.g. the 5c exceeding rate according to Böcking and the DNA index according to Atkin were found to be correlated with the tumour size (p less than 0.08%). These preliminary results indicate that the AgNOR number as well as the DNA features could be independent prognostic parameter in laryngeal squamous cell carcinoma, complementary to the staging categories.

Adult↗

The impact of nucleolar organizer regions for the lymph node spread and prognosis of invasive ductal mammary carcinoma.

In primary tumours of 40 patients with invasive ductal carcinomas the significance of nucleolar organizer regions (NORs) for metastatic spread to the axillary lymph nodes and for the prognosis was assessed. Silver-stained tissue sections were investigated by means of semiautomated image analysis. The nucleolar organizer regions of 100 tumour cell nuclei per specimen were measured. The number as well as the area of the NORs were evaluated together with morphometrical and DNA features, histopathological and clinical data. By means of multivariate discriminant analysis, significant differences between tumours of 20 node-negative and 20 node-positive patients could be found. The mean number of NORs was significantly higher in patients with lymph node metastases (p = 0.0059), whereas the mean area was significantly lower in node-positive patients. By using the NOR number as the only parameter both groups were classified with an overall efficiency of 95%. There was also a significant difference between long-term and short-term survivors by considering the mean number of NORs, but the Auer-type, the 2 cDl value, and the DNA-grade of malignancy were of better predictive value. Within the group of node-negative patients the NOR number was most suitable for distinguishing between good and poor prognosis, whereas within the group of node-positive patients once more the DNA parameters played the most decisive role for predicting prognosis. With regard to the small number of patients the results have to be considered as preliminary. Further investigations in a more extensive population are necessary.

Adult↗

[Morphological possibilities for objectification of the prognosis for invasive ductal carcinoma of the breast].

Tissue sections were taken from 187 cases of invasive ductal mammary carcinoma (among them 94 cases with lymph node metastases, average follow-up period being 44 months) and, after Feulgen staining, were investigated by automated microscopic image analysis. A comparison was made, with reference to survival periods, between the relevance to prognosis of nuclear image analysis and results obtained from histopathological grading, according to Bloom and Richardson (1957), as well as findings recorded from image analysis of DNA. Histopathological grading was found to be of poor reproducibility (71.1%). While statistically significant differences were found to exist between survival curves of Grades I and III patients, grading proved to be of minor importance to prognostic assessment of the individual case, with the number of G-II cases being relatively high (42.7%). Results of better reproducibility were achievable from the quantitative morphological method of nuclear image analysis. Its forecasting value with regard to good or poor prognosis was clearly higher than that of histopathological grading, and the number of cases with obscure or dubious prognosis was clearly lower (18.9%). DNA ploidy measurement, using DNA histogram types according to Auer (1980), has proved to be another method by which prognostically favourable and unfavourable cases can be distinguished from each other with statistical significance, though its classification quality (70.5%) still was unambiguously below that achievable by nuclear image analysis (79%).

Adult↗

Use of nuclear image cytometry, histopathological grading and DNA cytometry to make breast cancer prognosis more objective.

Feulgen-stained tissue sections of 187 invasive ductal carcinomas (94 with lymph node metastases; mean follow-up: 44 months) were studied using computer assisted image cytometry. Based on survival time, the prognostic significance of nuclear image analysis was compared with the results using conventional histopathological grading according to Bloom and Richardson, as well as with image cytometric DNA measurements. The histopathological grading has the disadvantage of poor interobserver reproducibility (71.1%). Despite statistically significant differences between the actuarial survival curves of grade 1 and grade 3 patients, the prognostic significance of the conventional grading method for individual patients seems to be low and the number of grade 2 cases (42.8%) is large. The quantitative morphological method for analyzing nuclear images gives more reproducible results. Compared to histopathological grading, the predictive values for good or poor prognosis are clearly higher and the number of cases with uncertain prognosis is significantly smaller (20.9%). DNA ploidy measurements also make it possible to distinguish statistically significant differences between favorable and unfavorable prognoses with respect to over-all survival time. However, the classification accuracy based on the best single parameter (DNA-histogram type according to Auer) is 70.2% compared with 78.9% for nuclear image analysis.

Breast Neoplasms↗

[Results of flow image analytic DNA determination in histologic preparations of malignant tumors].

The steadily increasing interest in DNA and ploidy determination of malignant tumours led to an increased application of flow image cytometric methods in tumour research and clinical pathology for some years. The investigations are mainly designed to explore the proliferative capacity and deviations in the characteristic DNA-content, finally to obtain clues about the actual malignancy grade and the prognostic outcome of a given malignant tumour therapy. The results of the study on 84 breast and 30 gastric cancers show the principal opportunity to use image cytometric techniques for DNA determination in histological sections. Apart from all disadvantages of these methods compared with flow cytometry, the image cytometry is capable of giving prognostic information with respect to survival as well as to the metastatic potential. Although several significant differences exist between the prognostic subgroups in seven and four DNA parameters, respectively, the case-related decision is not satisfying the clinical demands. Gastric cancers did not show any significant differences on the single-parameter level. Single distinct DNA parameters having the same diagnostic importance in both different tumour types and different prognostic problems could not be found.

Adenocarcinoma↗

[Cell nucleus analyses on the heterogenicity, proliferation and metastasis of malignant tumors].

The heterogeneity of primary and metastatic tumors was studied on the basis of their nuclear images. Feulgen-stained tissue sections of invasive ductal carcinomas of the breast (84 primaries, 15 lymph node metastases), adenocarcinomas of the stomach (30 primaries) and colorectal adenocarcinomas (30 primaries, 10 lymph node metastases) were investigated by high resolution image analysis. At least 150 tumour cell nuclei as well as 50 diploid reference cells were measured in each case. By means of multivariate statistical analysis significant differences could be found between primary tumors with and without lymph node involvement or distant metastases. In contrast, in a majority of the cases primary tumors and their metastases were largely identical with regard to the nuclear image and the DNA content. Features with high discriminant power for differentiation of metastasising tumors and malignant tumors without metastatic spread were the nuclear area, the number of coarse chromatin particles and other descriptors of the chromatin structure. The DNA content as a useful tool for the prediction of prognosis was of minor importance for the prediction of the metastatic phenotype.

Adenocarcinoma↗