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Biomedical subjects

F Theissig

Publications and source records attributed to F Theissig.

At least 19 recordsLinked to original sources

An experimental in vivo analysis of the resorption to ultrasound activated pins (Sonic weld) and standard biodegradable screws (ResorbX) in sheep.

We compared the healing and reaction in the mandibles of 11 sheep of a conventional bioresorbable screw osteosynthesis with the newly developed ultrasound-activated pin osteosynthesis. The thermal stress caused by insertion of the ultrasound-aided pins leads to no cellular reaction around the pin. There is neither clinical nor histological evidence of any initial inflammation that could have been induced by the insertion. Adequate attachment of fibrous tissue to the pin head and the absence of any inflammation are important preconditions for the introduction of this new method of osteosynthesis into clinical practice. Further advantageous characteristics are easy intraoperative handling and a reduction in operating time, because cutting the thread is not required. There must be sufficient interlinkage of the polymer and the trabecular structures to ensure stability.

Absorbable Implants↗

[Necrotizing lymphadenitis (Kikuchi-Fujimoto disease) as a rare cause of cervical lymphadenopathies. Diagnosis and differential diagnosis].

BACKGROUND: The ENT specialist is often confronted with the inquiry as to the cause of lymph node enlargements. Common causes include inflammations, neoplastic, or autoimmune diseases. We report on three cases of Kikuchi-Fujimoto disease as a benign self-limiting lymphadenopathy of unknown etiology, which is usually found in young women between 20 and 30 years of age. Main symptoms are indolent or light tender, enlarged lymph nodes in the neck area. The correct diagnosis requires the histologic examination of the lymph node. Even for the experienced pathologist the differential diagnosis of malignant systemic disorders can be difficult. PATIENTS: Three female patients suffering from Kikuchi-Fujimoto disease were treated in our department between September 1997 and March 1998. RESULTS: All patients showed indolent and enlarged lymph nodes in the neck. In one case we were able to diagnose an acute cytomegalovirus infection; in another case an acute Epstein-Barr virus infection. After 3-5 months the symptoms disappeared spontaneously in all patients. In two of the three cases, histologic lymph node examination revealed T-cell lymphoma and Hodgkin's disease and in one case led to initial chemotherapeutic treatment. As a result of a second histologic examination, both diagnoses were reviewed and Kikuchi-Fujimoto disease was diagnosed. Chemotherapy was discontinued. CONCLUSIONS: Kikuchi-Fujimoto disease is a benign, self-limiting lymphadenopathy which is usually diagnosed in young women. Distinguishing Kikuchi-Fujimoto disease from malignant systemic disorders may even be difficult for pathologists using histological examination techniques and requires close cooperation between the ENT specialist and the pathologist. In order to minimize the risk of misdiagnosis and incorrect treatment, the ENT specialist should inform the pathologist about the differential diagnosis of Kikuchi-Fujimoto disease in such cases.

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↗

Is systematic sextant biopsy suitable for the detection of clinically significant prostate cancer?

BACKGROUND: The optimal extent of the prostate biopsy remains controversial. There is a need to avoid detection of insignificant cancer but not to miss significant and curable tumors. In alternative treatments of prostate cancer, repeated sextant biopsies are used to estimate the response. The aim of this study was to investigate the reliability of a repeated systematic sextant biopsy as the standard biopsy technique in patients with significant tumors which are being considered for curative treatment. METHODS: Systematic sextant biopsy was performed in vitro in 92 radical prostatectomy specimens. Of these patients, 81 (88.0%) had palpable lesions. RESULTS: Of the 92 investigated patients, 70 (76.1%) had potentially curable pT2-3pN0 prostate cancers. In these patients, the cancer was detected only in 72.9% of cases by a repeated in vitro biopsy. In the pT2 tumors, there was a detection rate of only 66.7%. CONCLUSIONS: This study underlines the fact that a considerable number of significant and potentially curable tumors remain undetected by the conventional sextant biopsy. A negative sextant biopsy does not rule out significant prostate cancer.

Aged↗

[An unusual picture of insulinoma in type-2 diabetes mellitus and morbid obesity].

HISTORY AND CLINICAL FINDINGS: Marked hyperinsulinism was demonstrated in the course of an oral glucose tolerance test (oGTT) in a 63-year-old woman with severe obesity (height 1.59 m, body weight 123 kg, body-mass index 46.4 kg/m2). The diabetic metabolic state, first diagnosed 12 years ago, had been replaced by a low plasma glucose level: she often had attacks of ravenous hunger. A reducing diet of 800 kcal had not been tolerated. She had not had any syncopes. She had continually gained weight since puberty, but her weight had remained relatively constant for the past 5 years during which she had been treated with L-thyroxine for a diffuse goitre (stage II). INVESTIGATIONS: In the course of an oGTT (75 g glucose) the basal insulin concentration (146 pmol/l) had risen to 1663 pmol/l at 30 min. The basal proinsulin level was 50 times normal (66 pmol/l vs. 1.418 pmol/l), while the initial plasma glucose level had fallen from 4.3 mmol/l to 3.8 mmol/l. Spiral computed tomography of the pancreas showed a 3 x 2.5 cm mass in the region of the tail of the pancreas. TREATMENT AND COURSE: At laparoscopy a 4 cm tumor was palpated in the region of the pancreatic tail. Left resection of the pancreas was performed. Histopathological examination of the surgical specimen confirmed an insulinoma. A repeat of oGTT 6 months postoperatively demonstrated a markedly diminished insulin level compared with the preoperative results, as well as a diabetic metabolic state. CONCLUSION: In case of dramatic improvement of diabetes mellitus in an obese patient without drug treatment or weight reduction an insulin-producing tumour should be considered in the differential diagnosis. There may be no typical hypoglycaemic symptoms because of insulin resistance associated with the obesity.

Combined Modality Therapy↗

Remote quantitation server for quality assurance in DNA ploidy analysis.

OBJECTIVE: To remotely test a stepwise framework of quality control measures, developed according to the 1997 European Society of Analytical Cellular Pathology consensus on diagnostic DNA image cytometry, in two series of measurements by means of the quantitation server EUROQUANT. STUDY DESIGN: In each of these series, 104 fine needle aspiration biopsies, imprints from breast cancer specimens and 28 rat liver imprints were measured twice at two different cytometry workstations. Further measurements on special rat liver specimens for evaluation of the stability of the machinery and of the preparation process were done at both workstations. Afterwards the measurement data from both machines were transferred to the quantitation server and analyzed automatically. Beside the classical DNA histograms, a set of further evaluations was performed to detect optical errors as well as inhomogeneities in the measurements. Running values for mean integrated optical density values, mean corrective factors and mean coefficients of variations of corrective factors were computed to control the stability of the entire methodology over time. RESULTS: The study demonstrated the preconditions and outcome of server-based quality control in DNA ploidy analysis. The results show that such a remote analysis is feasible and comparable to local DNA ploidy analysis. It is also demonstrated how quality control tests reflect the process performance of ploidy analysis at its different levels. CONCLUSION: Quality control must be an inherent part of the daily routine to allow a reliable diagnostic interpretation and ensure steadily high product quality.

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↗

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↗

'Blind' multicenter evaluation of the prognostic value of DNA image cytometric and morphometric features in invasive breast cancer.

The prognostic value of classical prognosticators in 92 invasive breast cancers with long follow-up has been compared with a number of DNA-related image cytometric features (2c deviation index (2cDI)), Auer (histogram) type, 5c exceeding rate (5cER), DNA malignancy grade (MG), and the morphometrically assessed mitotic activity index (MAI) and mean nuclear area (MNA). The quantitative analyses were carried out without knowledge of the outcome nor of clinicopathological features. The cytometric analyses and assessments of MNA were performed on Feulgen stained, 4-microns thick tissue sections in Dresden. The MAI was assessed in Amsterdam. Thereafter, the survival data were matched with the classical variables, the cytometric features, the MAI and the MNA in univariate and multivariate analyses. Lymph node status (LN) and tumour stage were significantly different, tumour stage being the strongest discriminator between survivors and non-survivors (Mantel-Cox value = MC = 30.7, P < 0.0001). Grade was (just) significant (P = 0.05). The cytometric features, the MAI and the MNA were all highly significant prognosticators. The strongest cytometric feature was the Auer type followed by the 5cER, and the 2cDI. The MNA was also significant. The MAI was the strongest single prognostic factor in this blind analysis (MC = 50.8, P < 0.0001), and the MAI combined with the lymph node status, tumour stage and the cytometric features Auer type and 2cDI was the best multivariate combination (MC = 94.0). Separate analyses of the lymph node negative (LN-, n = 39) and positive (LN+, n = 53) groups showed that the 5cER and MAI were the most important in the LN- and the MAI in the LN+ patients.

Breast Neoplasms↗

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↗

[Syringocystadenoma papilliferum of the outer ear canal].

Ceruminomata are tumours spreading from the ceruminous glands of the external auditory canal. Since 1894 190 cases have been described, but nomenclature is still confusing to some extent. Syringocystadenoma papilliferum is a special subgroup. 189 cases are reported in the literature; 11 tumours have been observed in the auditory canal. A further case is reported in this paper.

Adenoma, Sweat Gland↗

Heterogeneity of the chromatin fine structure in DNA-diploid breast cancer cells.

The chromatin fine structure of Feulgen-stained DNA-diploid tumour cells was studied by means of image cytometry in fine-needle aspiration biopsies of 115 breast cancer patients. The investigation was focused on diploid, several subtypes of polyploid, and aneuploid tumours. Only the clearly separable diploid peaks of these tumours were measured cytometrically by an OPTIMAS-based image analysis system, which led to a set of 93 primary cytometric features in each diploid subpopulation. The results demonstrate that the diploid tumours are clearly different to the diploid compartments of various subtypes of polyploid and aneuploid tumours. Between those diploid subpopulations from polyploid tumours, chromatin structure differences also exist. A higher degree of similarity between polyploid and aneuploid tumours, compared to diploid, became evident. The actual structural differences between the diploid subpopulations indicate both increasing variances within the peak and increasingly coarse and contrasted, irregular chromatin structure with the occurrence of tetraploid, octoploid, and aneuploid DNA-histogram peaks. Therefore, the structural effects of an increasing genomic instability seems not to be restricted to the non-diploid cell populations.

Adenocarcinoma↗

Increase of precision and accuracy of DNA cytometry by correcting diffraction and glare errors.

In recent TV-based image cytometers considerable disproportionalities exist between the IOD values of reference cells, as well as diploid, tetraploid, and octoploid analysis cells compared with their theoretical IOD ratios. An important source of these deviations is the limited spatial resolution of the microscopic objectives, based on the effects of diffraction. Compared to these influences the glare is less important. A correcting method is given for reducing both effects on the DNA measurements, which considers a narrow region along the nuclear contour to be optically disturbed. The correction of this mean optical density (MOD)- and size-dependent geometric resolution error is applicable to any cell type. The method was tested on 25 rat liver imprints and 29 fine needle aspirates from breast cancers. The resulting stemline ratios are close to the theoretical ones. A further improvement was then reached by a glare correction. The slide-by-slide variations of stemline ratios, remaining after the corrections, were considered in a test statistic for defining the aneuploidy of a given stemline. Statistically based clear-cut decision rules were obtained for DNA histogram interpretation.

Animals↗

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↗