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Biomedical subjects

G Mikuz

Publications and source records attributed to G Mikuz.

At least 37 records · Page 2Linked to original sources

Nuclear chromatin texture analysis of nonmalignant tissue can detect adjacent prostatic adenocarcinoma.

BACKGROUND: The aim of this study was to investigate the possibility of identifying prostatic adenocarcinoma by nuclear chromatin texture feature analysis of adjacent histologically benign-looking tissue. METHODS: Two hundred and forty prostatectomy specimens were selected from the archives of the Department of Pathology, University of Innsbruck. These consisted of 67 cases of benign prostatic hyperplasia (BPH) and 173 cases of prostatic adenocarcinoma (PAC). The specimen collection was divided randomly into a training set and test set. Cytospin preparations of disaggregated cells prepared from paraffin-embedded material were stained specifically for DNA by the Feulgen method. For the cancer cases, only tissue that histologically appeared nonmalignant, from the vicinity of the lesion, was used in the sample preparation. Only normal-appearing diploid cell nuclei were analyzed from both the BPH and PAC groups. A discriminator comprised of three nuclear texture features to separate BPH from PAC cases was derived from the training set of cases, and then applied to the independent test set cases. RESULTS: PAC cases were separated from BPH cases with a sensitivity of 90% and a specificity of 97% on the independent test set of cases. CONCLUSIONS: This retrospective investigation demonstrates that by high-resolution image cytometry it is possible to detect the presence of prostatic adenocarcinoma with very high reliability when examining prostate samples that only contain histologically normal-looking cells. This method could become clinically relevant in identification of cancers missed by histologically negative core needle biopsies.

Adenocarcinoma↗

Epithelial tumours of the adult kidney.

The epithelial tumours of the adult kidney, in particular renal cell carcinoma (RCC), are a variety of neoplasms that can be classified by morphology and genotype. Although most are well characterised, typical and less typical tumour variants are recognised. There is evidence to indicate that stage is one of the most important prognostic factors, irrespective of tumour subtype. However, the appropriate handling of nephrectomy specimens is essential for accurate evaluation of diagnostic and prognostic factors in RCC. The problem of how to achieve more objective nuclear grading is still unresolved. The use of diagnostic decision support systems offers the possibility of a flexible approach to this problem, while still utilising morphological criteria. The histopathological analysis remains important, but new techniques of molecular and cell biology will be providing new tools of extraordinary power to sharpen the diagnosis and give it a biological interpretation.

Adult↗

Angiosarcoma of the testis.

A primary angiosarcoma of the testis in a 74-year-old patient was a highly anaplastic epthelioid angiosarcoma, which was positive for endothelial markers immunohistochemically. The tumour was unrelated to testicular germ cell neoplasm; the patient had received no previous radiation or chemotherapy.

Aged↗

Are nuclear texture features a suitable tool for predicting non-organ-confined prostate cancer?

PURPOSE: We investigated the possibility of determining organ confinement of prostate cancer using multiple nuclear texture features determined by fully automated high resolution image analysis combined with preoperative serum PSA levels. MATERIALS AND METHODS: The study population consisted of 145 patients (61 organ confined and 84 non-organ-confined cases). Nuclear texture features were determined using single cell preparations of radical prostatectomy specimens. Nuclear texture features were extracted and analyzed by multivariate logistic regression analysis in order to build a classifier for distinguishing between organ confined and non-organ-confined tumors. The classifier was designed in a cell by cell model and tested on a case by case analysis. RESULTS: The predictive probability of the trained classifier in the cell by cell analysis had a sensitivity of 63%, a specificity of 53%, a positive predictive value of 75% and a negative predictive value of 38% and an area under the ROC curve of 0.58. In the case by case analysis the sensitivity was 70%, the specificity was 54%, positive predictive value 78%, negative predictive value 74%, area under the ROC curve 0.62. When preoperative PSA was included in the algorithm, sensitivity raised to 80%, specificity to 60%, the positive predictive value raised to 79%, the negative predictive value to 52% and the area under the ROC curve to 0.70. CONCLUSIONS: In contrast to former studies using tissue sections, our results suggest that nuclear texture features extracted from single cell preparations cannot be used as a reliable parameter for the determination of organ confinement in prostatic adenocarcinomas.

Adenocarcinoma↗

Quantitative assessment of bladder cancer by nuclear texture analysis using automated high resolution image cytometry.

The aim of this study was to investigate the possibility of identifying urothelial neoplasia by nuclear chromatin texture feature analysis using high resolution image cytometry to improve the diagnostic accuracy of cytologic examination in the detection and monitoring of bladder cancer. Touch imprints of transurethral resection material of 56 control group (CG) cases of nonmalignant urothelium and 94 tumor group (TG) cases of bladder cancer were analyzed. The specimen collection was divided randomly into a training set and a test set. Cells were stained specifically for DNA by the Feulgen method. Only diploid cell nuclei were analyzed from both groups. A discriminator comprised of three nuclear texture features was derived from the training set of cases to separate CG from TG cases. This discriminator was then applied to the independent test set. CG cases were separated from TG cases with a sensitivity of 97% and a specificity of 95% on the independent test set of cases. When dividing TG cases into high-risk and low-risk groups, sensitivity in the low-risk group was 93%. None of the high-risk cases was misclassified (sensitivity, 100%). This retrospective investigation demonstrates that by high-resolution image cytometry it is possible to distinguish between urothelial neoplasia and normal urothelium with high reliability when examining diploid cell nuclei only. This method is superior to DNA ploidy analysis using image or flow cytometry and may become clinically relevant as a supplement to conventional cytologic examination. These promising results should be confirmed on cytologic preparations derived from bladder washings or voided urine.

Adult↗

Malignant large cell calcifying Sertoli cell tumor of the testis (LCCSCTT). Report of a case in an elderly man and review of the literature.

Malignant Large Cell Calcifying Sertoli Cell Tumor of the Testis (LCCSCTT) is a rare histological variant of sex cordstromal tumors. It usually arises in young males, sometimes is associated with endocrine abnormalities and has a benign course. It is exceptional in elderly men and the outcome is rarely fatal. We report a case of LCCSCTT in a 73 year-old man with fatal outcome. The tumor involved the right testis and several areas of the tunica albuginea were grossly invaded. Serum levels of HCG, LH and testosterone were normal. Lymphoangiography performed after orchiectomy showed an involvement of the iliac and preaortic lymph nodes. X-ray of the chest showed no lung metastases. A thorough study of the light microscopic, immunohistochemical and ultrastructural appearances was performed. Immunohistochemistry revealed positivity to vimentin, S-100 and NSE. Our observations confirm the previous findings concerning malignant LCCSCTT and point out the histogenesis of the tumor from Sertoli cells.

Age of Onset↗

The impact of FISH on our understanding of testicular tumour development.

The fusion of techniques of classical cytogenetics and molecular biology has led to the establishment of the fluorescence in situ hybridization (FISH) technique. This method, allowing detailed chromosomal investigations in metaphase spreads as well as in interphase nuclei, has enabled pathologists to detect molecular changes in precancerous lesions such as carcinoma in situ of the testis. In particular, its application to paraffin material has allowed the correlation of chromosomal aberrations with morphological and immunohistochemical characteristics. Thus, recurrent chromosomal aberrations found in invasive testicular tumours, such as the occurrence of an isochromosome i(12p), are already present in preinvasive stages, indicating an early event in carcinogenesis. Recent work, published in this issue, presents the diagnostic impact of these investigations.

Carcinoma in Situ↗

Microvessel density in core biopsies of prostatic adenocarcinoma: a stage predictor?

Microvessel density was recently reported to be an independent correlate of tumour stage in whole mount prostatectomy specimens. This prompted an investigation of whether the quantitation of tumour microvessels could also be reliably applied to prostatic core biopsies, as a presurgical determinant of local tumour extension. The study was performed on a series of 46 unselected patients with prostatic adenocarcinomas undergoing radical prostatectomy. Intratumoural microvasculature was highlighted immunohistochemically using an antibody against CD31 and subsequently evaluated at x 400 magnification in both biopsies and corresponding prostatectomies. The highest microvessel count was reported for each case. Ten cases (22 per cent) had to be excluded because of insufficient measurable tumour areas in core biopsies. The remaining 36 cases (16 pT2; 20 pT3) showed a high degree of correlation between microvessel density in biopsies and prostatectomies (P < 0.0001). Similarly, pre- and post-operatively determined microvascular counts correlated well with tumour stage (P < 0.0001). Furthermore, the median microvessel density in core biopsies and tumours, i.e., 34, distinguished well between organ-confined and organ-extending tumours (positive predictive value for pT3 tumours 94.4 per cent; sensitivity 85 per cent). These data indicate that the evaluation of microvessels in core biopsies, eventually combined with other parameters, could be a reliable method for the individual prediction of the post-surgical tumour stage of prostatic adenocarcinoma.

Adenocarcinoma↗

Non-Hodgkin lymphoma with exclusive involvement of the heart and the gastrointestinal tract.

An extranodal high-grade B-cell lymphoma, centroblastic type, with exclusive involvement of the heart, stomach and small bowel was detected at post-mortem examination following the death of an 80-year-old man. Autopsy revealed massive cardiomegaly with a total heart weight of 1800 g owing to an intramyocardial tumour involving the right ventricle, and multiple mucosal tumour plaques and nodules in the stomach and small bowel. The case highlights the difficulties of diagnosing cardiac lymphoma clinically even in the presence of a large tumour mass.

Aged↗

Pathology of prostate cancer. Old problems and new facts.

Based on autopsy and epidemiologic data the lifetime risk of developing prostate cancer for a 50-year-old man is 42%, but only 9.5% will develop a clinically manifest disease and only 2.9% will die from this disease. The actual rate of carcinoma detection using PSA, digital rectal examination and transrectal ultrasound is 1%-3%. The majority of prostate carcinoma never progress to clinically significant disease, a minor portion remains confined to the prostate for many years and other carcinomas progress rapidly to a life threatening disease. The dilemma for clinicians and pathologists dealing with this tumor is how to distinguish these three biologically different types. Pathologists play an important role in preoperative diagnosis and in the postoperative prognosis oriented evaluation of the prostatectomy material. Volunteer PSA screening trials have led to an enormous increase in core-needle biopsies of the prostate. Since biopsies are often performed in men without palpable or ultrasound-visible nodules, are now faced with an increasing number of equivocal morphological features which can not be clearly defined, even with standardized criteria. Further investigations are also required to elucidate the clinical importance of PIN detection in biopsies. The heterogeneous histomorphology of prostate carcinoma can not be used as a prognostic factor. Therefore the histological grading is a very important factor for the assessment of prognosis. Carcinoma grading in biopsies is also of limited value in predicting tumor stage. Currently, several different grading systems are in use. Gleason's grading is the most favored, although its reproducibility is very low. The stage of the prostate carcinoma is still the best prognostic factor. In order to accurately assess the pTNM stage, TUR or prostatectomy material must be subject to extensive and standardized processing. Additionally, the volume of the tumor, the vascular invasion, the amount of extension of the tumor through the prostate capsule and perhaps the neoangiogenesis might be valid prognostic factors for disease progress and for survival. The value of novel methods (p53, bcl-2, apoptosis, microvessel density, interphase cytogenetics, androgen receptor mutation, neuroendocrine cells, E-Cadherin) remains to be proved. DNA ploidy is a good prognostic factor after prostatectomy and can be used to plan adjuvant hormone therapy.

Journal Article↗

Expression of vimentin, cytokeratin, and desmin in Sertoli cells of human fetal, cryptorchid, and tumour-adjacent testicular tissue.

The intermediate filament of mature human Sertoli cells is vimentin. A co-expression of vimentin together with cytokeratin has been demonstrated in Sertoli cells during embryonal development and under pathologic conditions in adult testes. We analysed the presence of vimentin, cytokeratin, and desmin in Sertoli cells of fetal testes (n=20), in seminiferous tubules of cryptorchid testes (n=10) and adjacent to testicular germ cell tumours (n=47) using specific monoclonal antibodies and single and double-labelling immunohistochemistry. During embryonal development prominent cytokeratin expression disappears after the 20th week of gestation. Interestingly, we also found desmin in immature intratubular Sertoli cells between weeks 11 and 14. In adult cryptorchid testes and in peritumour tubules, desmin was also prominently present in Sertoli cells in the vast majority of the cases investigated, as well as vimentin and cytokeratin co-expression. This first description of desmin immunoreactivity may shed some light on the ontogeny of human Sertoli cells and demonstrates that this cell type is able to express three types of intermediate filaments in a complex manner.

Adult↗

CD30 expression in seminoma.

In testicular germ cell tumors the CD30 antigen has been shown to be regularly expressed in embryonal carcinoma and was thus suggested as a marker for this particular neoplasm. Very recently, it has been proven that the monoclonal antibody Ber-H2 is suitable for the detection of this membrane antigen in paraffin sections. We conducted an immunohistochemical study to investigate the CD30 expression in a large series of different presentations of seminoma (ie, pure, mixed, and spermatocytic) because there is evidence from several sources that embryonal carcinoma is histogenetically closely related to, and probably derives from, seminoma. Sections from formalin-fixed, paraffin-embedded tissue from 38 cases of testicular seminomas were immunostained for the demonstration of the CD30 antigen using the monoclonal antibody Ber-H2, cytokeratins, and placental alkaline phosphatase following an indirect streptavidin-peroxidase regimen. In selected cases, immunostainings were performed on consecutive sections to investigate a possible colocalization of CD30 and cytokeratins in seminoma. Specific immunostaining for CD30 in seminoma cells could be detected in single minute foci in 4 of 21 cases of pure classic seminoma. Seminomatous components of mixed tumors showed CD30 positivity in single, but also multiple, foci in 7 of 14 cases. CD30 immunoreactivity in seminoma cells occurred with and without colocalized expression of cytokeratin. Spermatocytic seminoma (n = 3) as well as intratubular germ cell neoplasia in tumor adjacent parenchyma (n = 36) were negative in all cases investigated. We conclude that in testicular germ cell tumors, the expression of CD30 is not restricted to embryonal carcinoma but can also be found focally in seminoma, adding further evidence for a close relationship between these two tumors. The prevalence of CD30 expression in seminomatous components of mixed tumors, as well as the coexpression with cytokeratins, suggest that CD30 expression in seminomas might indicate their upcoming transformation to embryonal carcinoma. This conclusion coincides with a model featuring seminoma in a central role of germ cell tumor development.

Adolescent↗

What do physicians think of telemedicine? A survey in different European regions.

To discover the perception of telemedicine in a sample of physicians not yet participating in telemedicine networks, a questionnaire was sent to doctors in different European countries. The questions covered various general aspects of telemedicine. The percentage of questionnaires returned ranged from 12% (Central Europe) to 27% (Spain). Apart from the rather disappointing response rates the results document a strong interest in telemedicine on the part of the physicians surveyed. Knowledge of the existence of telemedicine was high. Most of the respondents would have liked to have had their clinic's telemedicine system in their own laboratory. More than 50% of the physicians thought that their work would be improved by using telemedicine. Respondents from Central Europe were significantly less enthusiastic about telemedicine than those from other regions. However, the answers to the majority of the questions were similar in the different groups.

Attitude of Health Personnel↗

[The legal status of telemedicine in Austria].

The rapid development of modern communication technologies offers new opportunities for medical diagnosis and treatment. In spite of the obvious theoretical benefits of telemedicine, which have been proven by many projects in practice, telemedicine has not become generally established in Europe. Besides lack of technical standardisation and high purchase costs, one of the reasons might be the as yet unclarified legal situation. Taking the present legal situation in Austria we tried to explore questions of liability concerning telemedicine. The outstanding point seems to lie in the contract between the participating physicians on the one hand and between the physicians and the patient on the other hand. If the consulting physician is self-employed he has to take responsibility for any error on the part of the consulted physician. However, if he is working in a hospital, then he is legally considered an "Erfüllungsgehilfe" (person employed by the debtor in the performance of his obligation) an any further doctor consulted is automatically also an "Erfüllungsgehilfe" of the hospital and therefore the hospital takes responsibility for any mistakes made by the consulted physician. Although there has not been any specific jurisdiction concerning telemedicine in Austria, the present legal provisions are adequate for reaching decisions on questions of liability, so that there are no objections from the legal point of view to the general implementation of telemedicine.

Austria↗

IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells.

Malignant ascites of epithelial ovarian cancer patients contains high levels of interleukin 6 (IL-6). The present study was conducted to compare the secretion of IL-6 by seven different human ovarian cancer cell lines (OVCA) and cultured human peritoneal mesothelial cells (HPMC) and to examine the regulation of its production by other cytokines. IL-6 was detected in supernatant medium of all mesothelial cell cultures (8/8) and 6/7 ovarian cancer cell lines. Levels of IL-6 secreted by HPMC (median 27,100 pg/1 x 10(5) cells; range 3870-168,200) were 590-fold higher (P < 0.01) than those secreted by OVCA (median 46 pg/1 x 10(5) cells; range 0-16,450). Treatment with TNF-alpha or IL-1 beta (both 10 ng/ml) for both types of cells and both cytokines resulted in a significant (P < 0.05) elevation of IL-6 production. In OVCA IL-6 secretion was increased 7- and 39-fold and in HPMC 6- and 8-fold, respectively. Under TNF-alpha treatment IL-6-levels secreted by HPMC were 149-fold higher (P < 0.01) than those generated by OVCA. Similarly, IL-1 beta-induced IL-6 levels were 102-fold higher in HPMC (median 288,800 pg/1 x 10(5) cells; range 93,125-552,800) than in OVCA. IFN-gamma (10 ng/ml) increased IL-6 generation in OVCA (6-fold) but not HPMC. The proliferation of both cell types however, was significantly (P < 0.05) inhibited by IFN-gamma. Our results suggest that peritoneal mesothelial cells may be a prominent source of IL-6 in ovarian cancer-related ascites.

Ascites↗

Solitary giant xanthogranuloma and benign cephalic histiocytosis--variants of juvenile xanthogranuloma.

Sequential biopsies taken from a patient with a solitary giant xanthogranuloma, an exaggerated macronodular (> 5 cm in diameter) variant of juvenile xanthogranuloma, and from a patient with benign cephalic histiocytosis, revealed a characteristic time sequence of histopathological findings. Early stages of the diseases showed a monomorphous infiltrate of mononuclear vacuolated histiocytes positive for KiM1p, HAM56 and factor XIIIa and were characterized by clusters of comma-shaped bodies. This was followed by a polymorphous mixture of various mononuclear and multinucleate histiocytes additionally labelling with KP1 (CD68) and, in occasional cells, for the adherence of peanut agglutinin. A variety of ultrastructural changes were found, including dense and regularly laminated bodies or lipid droplets. Our findings indicate that both entities are variants of a xanthogranulomatous reaction.

Antibodies↗