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Biomedical subjects

S Biesterfeld

Publications and source records attributed to S Biesterfeld.

At least 73 records · Page 4Linked to original sources

DNA grading of malignancy in breast cancer. Prognostic validity, reproducibility and comparison with other classifications.

The prognostic significance of the "DNA malignancy grade" (DNA-MG) was tested in a series of 104 breast cancer patients in comparison with TNM staging, histomorphologic grading according to Bloom and Richardson, mean nuclear area (MNA) and DNA-histogram classification according to Auer. The reproducibility and representativity of the grading systems were investigated, and their results in primary tumors and lymph node metastases were compared. The scalar DNA-MG was assessed on monolayer smears prepared from paraffin-embedded tissues; the smears were automatically Feulgen stained and used for rapid interactive DNA cytometric evaluation by an automated microscope and a TV image-analysis system. TNM staging showed the highest correlation with survival, followed by histomorphologic grading and DNA-MG; MNA and the DNA-histogram classification failed to give statistically significant prognostic information. Both histomorphologic grading and DNA-MG were identified as parameters adding independent prognostic information to the TNM staging. However, only DNA-MG demonstrated an acceptable reliability, with small 95% ranges between repeated measurements within the primary tumor (+/- 0.3 DNA-MG) and a strong correlation between the results in the primary tumor and its lymph node metastases. These findings show that the DNA-MG is a valid and reliable prognostic index that adds significant prognostic information to TNM staging.

Aged↗

Suitability of incorporated vascular stents for surgical patch-plasty: an experimental study.

PURPOSE: Evaluate the feasibility of expanding arterial and venous stents incorporated into the vessel wall by surgical patch-plasty in an experimental study. METHODS: An 8-mm Wallstent was percutaneously implanted into the carotid artery of 11 sheep and into the ipsilateral jugular vein in three of them. Three months after implantation, a patch-plasty was performed on the incorporated stents using a 0.4-mm-thick synthetic patch made of polytetrafluoroethylene (PTFE). Stent patency was monitored by color-coded duplex ultrasound and angiography for 6 months after operation. RESULTS: No suture dehiscence or aneurysm formation were observed. Nine of 11 arterial and 2 of 3 venous stents remained fully patent during follow-up. In arteries, complications encountered were a complete stent thrombosis early after surgery, as well as a floating thrombus in the stent, found at final angiography after 6 months. In veins, one partial stent thrombosis was observed. Microradiographic and histological examinations revealed marked intimal hyperplasia in both arterial and venous stents. Intimal hyperplasia was significantly more pronounced in patched than in stented arterial segments (p < 0.005). CONCLUSION: Patch-plasty surgery of previously incorporated vascular stents is technically feasible. Mid-term patency rates were acceptable.

Aneurysm↗

Puncture of stents implanted into veins and arteriovenous fistulas: an experimental study.

PURPOSE: Puncture of venous Wallstents and nitinol stents with dialysis needles was tested in an animal study. METHODS: In 15 sheep, divided into a group with prior surgical unilateral carotid-jugular shunt creation (9 sheep) and a second group without shunt creation (6 sheep), a self-expanding nitinol stent and/or a Wallstent were bilaterally placed into the jugular veins. After 1 month, 10 nitinol stents and 9 Wallstents were punctured weekly with a 15-gauge cannula over a period of 15 weeks. Stent patency was followed up by color-coded duplex ultrasound and angiography. After sacrifice, high resolution X-rays of the removed vessels were taken to assess stent deformation. From histological slices, neointimal thickness inside the stents was measured and analyzed statistically. RESULTS: Puncturing of both the nitinol stent and the Wallstent was technically feasible. Stent deformations were not found. One stent stenosis, probably related to puncture, was observed. The pattern of intimal hyperplasia differed between the nitinol stent and the Wall-stent. Outward bulge of the vascular layers over the stent struts was greater in nitinol stents. In the relevant area in between the stent struts there was no significant difference in intimal thickness between the two types of stents. Intimal thickness was more pronounced in shunted than in nonshunted animals only in the Wall-stent subgroup (p = 0.025) and more pronounced in punctured than in nonpunctured stents only in the nitinol stent subgroup (p = 0.018). CONCLUSION: Puncturing of stents was feasible without major short-term complications. Therefore, stent implantation into the punctured segment of a hemodialysis fistula may be indicated if there is no alternative treatment.

Alloys↗

Neointimal hyperplasia in low-profile Nitinol stents, Palmaz stents, and Wallstents: a comparative experimental study.

PURPOSE: To compare neointima formation following insertion of low-profile Nitinol stents, Palmaz stents, and Wallstents. METHODS: Nitinol stents, Palmaz stents, and Wallstents similar in size were transfemorally inserted into the iliac arteries of 12 sheep. Four stents per sheep were deployed; the position of the stents was varied so that each type of stent was placed in each position (right or left, proximal or distal) with equal frequency. Stent patency was followed by angiography. Six sheep were euthanized after 1 month, and the remaining six after 6 months. Iliac arteries were removed en bloc and prepared for histological examination. Neointimal and medial thickness were measured by light microscopy, and measurements were analyzed statistically. RESULTS: Mean neointimal thickness both over (NO) and between (NB) the stent struts was greater in Wallstents (NO = 0.341 mm, NB = 0.368 mm) than in the Nitinol (NO = 0.260 mm, NB = 0.220 mm) and Palmaz stents (NO = 0.199 mm, NB = 0. 204 mm), but differences were not significant (p > 0.05). Medial atrophy in the area between the stent struts was greater in Wallstents compared with Nitinol and Palmaz stents (p < 0.007 and p < 0.02, respectively); in the area under the stent struts there was a significant difference only between Palmaz stents and Wallstents (p < 0.02). CONCLUSION: Under defined experimental conditions, none of the three types of stent appears to be preferable to the others regarding neointima formation in the short- to mid-term follow-up period.

Alloys↗

Percutaneous fragmentation of pulmonary emboli in dogs with the impeller-basket catheter.

A new catheter system for rapid percutaneous fragmentation of pulmonary emboli was tested in nine dogs. The system consisted of a high-speed rotating impeller, placed within the center of a self-expandable basket. Preformed radiopaque emboli were introduced via the right external jugular vein. In nine tests in five dogs, a single embolus was launched after the right pulmonary artery had been balloon occluded and the impeller-basket catheter had been positioned into the left pulmonary artery. Seven of nine emboli were completely fragmented, each within less than 10 s. In two tests, performed in two different dogs, the catheter was positioned after complete embolization of the left pulmonary artery. In both cases, the central pulmonary arteries could be fully, and the segmental arteries partly, recanalized. Mobility of the system within the pulmonary arteries was limited. There was no evidence of wall damage at the rotation site of the impeller. Free serum hemoglobin did not increase after treatment. We conclude that the device can be safely operated in the left pulmonary artery system of dogs. It causes no significant hemolysis, and is able to accomplish rapid recanalization of the central arteries. Due to limited steerability, occluded side branches cannot be treated consistently.

Animals↗

Effectiveness and safety of ultrasonic atherosclerotic plaque ablation: in vitro investigation.

Ultrasound energy was applied to 137 segments of human cadaver atherosclerotic arteries, 90 with calcified and 47 with noncalcified atheromatous plaque, and to 100 segments of healthy swine aorta. The average depth of penetration was dependent on the forward force of the ultrasonic probe, the duration of treatment, and the degree of atherosclerosis. There was one perforation of a fibrous plaque using a forward force of 2 Newton and 45 sec of application time. Injury of healthy intima was minimal. It is concluded that catheter-delivered ultrasound is effective and safe for the disintegration of atherosclerotic plaques. Presently, the main limitations of the system are the lack of flexibility and steerability.

Angioplasty, Balloon↗

Prognostic significance of vascular endothelial growth factor expression in ovarian cancer patients: a long-term follow-up.

The purpose of the study was to determine vascular endothelial growth factor (VEGF) concentrations in ascites from ovarian cancer and to correlate these data with VEGF expression in ovarian tumors, serum VEGF concentrations, and clinicopathologic characteristics. Ascites, serum, and tumor tissue from 65 ovarian carcinomas and eight borderline tumors were collected. VEGF concentration in peritoneal fluids and sera was determined using enzyme immunoassay. VEGF tumor expression was evaluated immunohistochemically. Significantly higher VEGF concentrations were found in ascites from malignant tumors (median, 2575 pg mL(-1)) compared with borderline tumors (median 181.9 pg mL(-1)) and benign peritoneal fluid (184.5 pg mL(-1)). Both VEGF ascites concentration and tumor expression correlated with advanced tumor stages and ascites volume. Elevated VEGF ascites levels were negatively correlated to patient survival. No differences between VEGF serum levels could be observed between ovarian cancer patients and patients with benign cysts. This study showed for the first time the clinical significance of elevated VEGF ascites level in ovarian carcinomas. VEGF is expressed by ovarian tumor cells and locally released in the malignant peritoneal fluid but is not increased in the serum of preoperative ovarian cancer patients. The enhanced VEGF level support novel therapeutic perspectives by VEGF inhibition.

Adenocarcinoma↗

Quantification of nitrifying bacterial populations in a full-scale nitrifying trickling filter using fluorescent in situ hybridization.

Fluorescent in situ hybridization (FISH) was used to quantify the ammonia-oxidizing populations within intact biofilm samples collected from a full-scale nitrifying trickling filter (NTF). Ammonia, nitrite, and nitrate concentrations were measured for aqueous samples taken in conjunction with biofilm samples at multiple filter depths. Correlation coefficients for individual sampling events, calculated by simple linear regression of FISH signal area and ammonia removal rates, ranged from 0.558 when using probe NEU23a to 0.982 when using probe Nso190. The improved correlations with Nso190 suggest that genera other than Nitrosomonas are present in this system. Percent biofilm coverage, as determined by 4',6-diamidino-2-phenylindole counterstaining and dry weight biomass measurements, did not change throughout the NTF. This indicates that biofilm growth is fairly uniform throughout the filter even if nitrifier growth is not.

Ammonia↗

Absence of epidermal growth factor receptor expression in squamous cell carcinoma of the uterine cervix is an indicator of limited tumor disease.

The expression of growth factors is considered as an important diagnostic and prognostic feature in tumor pathology. We investigated the value of the immunohistochemical EGF-receptor expression (EGF-R) in 30 squamous cell carcinomas of the uterine cervix, treated by radical hysterectomy and lymphadenectomy according to the Wertheim-Meigs-Okabayashi technique. Immunohistochemical reactions were performed on 4 microm sections from paraffin-embedded tissue, using an indirect peroxidase method. The staining results were evaluated semiquantitatively as negative (n=9; 30%) or as slightly, moderately or severely positive (n=21; 70%). The EGF-R-negative tumors were found in less advanced tumor stages. None had invaded into the parametrium (100%), eight were staged as T1 (89%), seven as N0 (78%), and seven showed no evidence for lymphangiosis carcinomatosa (78%). The respective values for the EGF-R-positive tumors ranged from 52% to 67%. However, only the difference in parametral invasion (EGF-R-negative: 0%, EGF-R-positive: 38%) was statistically significant (p=0.0306), probably due to the small number of cases. The EGF-R-expression was not correlated to histomorphological tumor grading. The results of this study indicate an inverse correlation between EGF-R expression and tumor spread. Assuming that this trend could be confirmed by a larger group of patients, immunostaining for EGF-R in a tumor biopsy could be useful to adapt surgical strategies and adjuvant therapy in the individual patient. Moreover, the EGF-R is an interesting target for immunotherapeutic approaches in squamous cell cervical carcinoma.

Adult↗

Immunohistochemical analysis of prostate-specific antigen does not correlate to other prognostic factors in breast cancer.

BACKGROUND: Prostate-specific antigen (PSA) is found in 30-40% of female breast tumors, as recently described. Diamandis and co-workers could demonstrate that PSA correlate significantly to a relapse-free survival and lower tumor stages in patients with breast cancer using a time-resolved immunofluorometric analysis. The presence of PSA in these tumors seems to reflect a favourable prognostic marker for that disease. The aim of our study was to evaluate the role of PSA as a prognostic factor in breast cancer using an immunohistochemical technique. MATERIALS AND METHODS: The PSA immunoreactivity of tissues from one-hundred women with malignant breast tumors was correlated to tumor staging, histomorphological tumor type, and biochemical estrogen and progesterone receptor content. Additionally, survival analysis was performed according to Kaplan and Meier. RESULTS: 49% of the tumors revealed positive staining for PSA. No significant correlation between PSA and the other parameters, or the mean survival time (PSA pos.: 5.3 years, PSA neg.: 5.4 years) could be demonstrated. CONCLUSIONS: As there were no significant correlations between PSA and other prognostic markers, PSA detected by immunohistochemistry seems not to be helpful in prognostic evaluation of breast cancer.

Biomarkers, Tumor↗

Expression of CD44(v5-10) splicing variants in primary ovarian cancer and lymph node metastases.

BACKGROUND: This study was designed to detect the expression of CD44v splicing variants in primary ovarian carcinomas and their lymph node metastases, in order to evaluate the possible role in intraperitoneal and lymphogenic metastasization. MATERIAL AND METHODS: Paraffin-embedded tissue of 50 patients with ovarian cancer was available from both the primary tumors and from the lymph node metastases. The expression of the CD44 standard from (CD44s) and of the variant isoforms CD44v5, CD44v6, CD44v7 and 8, and CD44v10 was investigated in the tumor cell regions by immunohistochemistry. RESULTS: 45/50 (90%) primary ovarian carcinomas were found to be immunohistochemically positive for the CD44v5 splicing variant; 10 (20%) tumors expressed both CD44v5 and CD44v6. Apart from an additional v7 stain, all of the ovarian carcinomas studied were negative for the splicing variants v7, v7-8 and v10. No differences were revealed in the pattern of CD44 variants expression investigated in primary tumors and in the lymph node metastases. CONCLUSIONS: In ovarian cancer the expression of CD44v5 as a possible first step, as well as CD44v6, probably plays an important role in intraperitoneal implantation. In view of the comparatively heterogeneous expression patterns of CD44v in individual organs, it may be assumed that there are organ-specific differences in this respect, and that the invasion potential is influenced by both the expression pattern and the extent of expression.

Adult↗

Re-evaluation of prognostic mitotic figure counting in breast cancer: results of a prospective clinical follow-up study.

Some years ago we were able to confirm reports on the prognostic meaning of mitotic figure counting in breast cancer on a retrospective series of 104 breast cancer cases (Hum Pathol 26: 47-52, 1995). An independent influence of mitotic figure counting on prognosis could be proven in stage I and stage II tumors. Using the same methodological approach, the investigation has been repeated recently on a prospectively collected series of breast cancer patients (n = 108). A strong benefit for the patients' outcome was found for patients with stage II tumors (p = 0.0093), but not for patients with stage I tumors (p > 0.05). Regarding the differences between the two studies, most probably the effects of therapeutic changes between the late 1970s and the late 1980s and aspects of the patients' selection may be responsible.

Aged↗

Diagnosis of bronchial carcinoma on sections of paraffin-embedded sputum. Sensitivity and specificity of an alternative to routine cytology.

The diagnostic accuracy of sputum cytology for the diagnosis of bronchial carcinoma using paraffin-embedded, serially sectioned and hematoxylin and eosin-stained specimens was tested in 4,297 sputum samples from 1,889 patients, 219 of whom had bronchial carcinoma. The diagnostic sensitivity depended mainly on the number of investigated samples and was 85.4% with three sufficient sputa. The sensitivity was not influenced by the histologic types, location or TNM stage of the tumor. The specificity of the method was 99.5%. In three cases localization of sputum cytologically diagnosed bronchial carcinomas was not possible immediately (occult carcinomas, pTx); in two of these cases the bronchial carcinomas were located during follow-up. The third patient died without verification of the cytologic diagnosis. According to our results, sputum cytology on serial sections is a valuable instrument for mass screening of high-risk groups for the early detection of bronchial carcinoma. Lower sensitivities of sputum cytology in mass screening programs for the early diagnosis of lung cancer are discussed critically.

Carcinoma, Bronchogenic↗

Differential diagnosis and evaluation of the clinical course of transurethrally resected T1G3 urothelial carcinoma of the bladder by DNA image cytometry.

The value of DNA image cytometry in the differential diagnosis of 106 T1G3 urothelial carcinomas of the bladder and the long-term prognosis (recurrence-free interval, survival) of the patients was tested in comparison with Ta/T1G1 (n=30) and Ta/T1G2 carcinoma (n=54). Monolayer smears were prepared from three 50-microm-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen at random, was determined using a TV-image analysis system CM-1 (Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every individual case. Different DNA cytometric parameters and the mean nuclear area were calculated. In comparison with G1- and G2-cases, the mean values of all DNA cytometric variables were markedly increased in the group of T1G3 cases, most obviously for the 5cEE, the mean ploidy and the ploidy imbalance (0.0006 > or = p > or = 0.0001). However, a remarkable overlay of the data distribution had to be considered. An aneuploid DNA stemline ploidy was highly characteristic for T1G3 urothelial carcinoma (sensitivity: 92%), but not sufficiently specific (57%). However, if increased values for the mean ploidy, the 2cDI, the 5cEE or the 9cEE (specificity: 86%-89%) were present additionally, the diagnosis of a T1G3 urothelial carcinoma could be made cytometrically. Follow-up data for survival (recurrence) analysis was available for 90 (82) patients of the T1G3 group. Using the median value as threshold, significant differences in survival were found for the mean ploidy only (p=0.0353). The length of the recurrence-free interval was significantly different for the entropy (p=0.0205), the 2cDI (p=0.0309) and the mean ploidy (p=0.0442). In conclusion, DNA single cell cytometry represents a highly relevant tool in the objective identification of T1G3 urothelial carcinoma of the bladder, with a sufficient sensitivity and specificity. Further, this method enables prediction of tumor recurrence if suitable variables are chosen. The long-term survival of patients with T1G3 urothelial carcinoma can be estimated by DNA cytometry only in a limited manner, possibly due to the fact that the causes of death in the mostly elderly patients will be independent from the limited tumor disease.

Aged↗

Detection of high risk patients in chronic myelogenous leukemia by DNA-image cytometry.

Peripheral blood smears from the time of diagnosis of 64 patients with chronic myelogenous leukemia (CML) in chronic phase were restained according to Feulgen. Nuclear DNA content of at least 100 myeloblasts and promyelocytes was measured by interactive DNA-cytometry using a TV-image analysis system, combined with an automated microscope. From the resulting DNA values the DNA parameters stemline ploidy, stemline shoulder fraction and "proliferative" fraction, which reflect cytogenetic and cell kinetic characteristics of CML, were derived. Each of these DNA parameters identified subgroups with a significantly different survival time and duration of chronic phase. Indicators for a good prognosis were a near-diploid stemline ploidy (median survival time 49 v. 26 months), a low percentage of nuclei in the stemline shoulder fraction (45 v. 28 months) and a high "proliferative" fraction (45 v. 23 months). Independently of clinical and hematological features, the DNA-cytometric parameters yielded additional prognostic information both in the univariate and multivariate analysis.

Adult↗

Healing of bone defects in combination with immediate implants using the membrane technique.

Twenty Brånemark implants were placed with membranes (Gore-Tex Augmentation Material) as immediate or delayed implants in the extraction sockets of 15 patients. Membrane perforations through the mucous membrane occurred in 10 patients after 6 to 24 weeks and once after 2 weeks. Histologic examination of 15 tissue samples taken when the membrane was removed showed genuine bone regeneration in three patients, connective tissue regeneration with intermittent bone regeneration in eight patients, purely fibrous healing in two patients, and inflammatory granulation tissue in two patients. The high proportion of membrane perforations with immediate implants should be taken into account in the assessment and clinical application of this therapy principle.

Alveolar Process↗

Principal component analysis. A factor analytical technique for the determination of interobserver variation in histomorphologic tumor grading.

The insufficient interobserver reproducibility limits the practical use of histomorphological tumor grading in daily routine pathology. In this study, the reasons for the quite low rates of agreement between different observers have been investigated by the application of a factor analytical technique, i.e. principal component analysis with varimax rotation, on a tumor grading system. Grading results from 44 cases of G1 and G2 giant cell tumors of the bone (GCT), graded by three different observers according to the five criteria of Jaffe, were taken as an example. It could be proven that the single criteria were used in an observer-specific way. Two criteria, for example, which are scored highly correlated by one observer, may be used independently by another. The resulting observer-specific different recognition patterns may provide an explanation for their quite different grading results, which were identical in only 48.6% to 54.1% (mean: 50.9%) of the cases. No correlation of GCT grading with recurrence was found in 31 cases which had been treated by intralesional surgery.

Adult↗

Interobserver reproducibility of immunocytochemical estrogen- and progesterone receptor status assessment in breast cancer.

The interobserver reproducibility in the immunocyto-chemical assessment of estrogen- and progesterone receptor status was investigated in a series of 102 cases of primary breast carcinomas. Immunostaining was performed on 4 microns cryostat sections using estrogen- and progesterone immunocytochemical assays (ER-ICA and PR-ICA) with methylgreen counterstaining. The slides were evaluated independently by two observers. The proportion and staining intensity of ER- or PR-positive tumor cells in areas of invasive tumor growth was subjectively assessed based on the examination of the entire slide. Scoring was performed according to the proposals of Remmele and Reiner. Additionally, the cytosol estrogen- and progesterone receptor content was determined by a standard dextran-coated charcoal (DCC-) assay. Observer 1 interpreted 60 (59%) of the ER-stained specimens and 50 (49%) of the PR-stained specimens as receptor-positive; for observer 2 the respective values were 59 (58%) for ER-stained specimens and 51 (50%) for PR-stained specimens. Positive biochemical receptor status was found in 68 cases with the ER-DCC (67%) and in 47 with the PR-DCC (46%). The interobserver agreement between the two observers on the immunocytochemical receptor status was 89% for the estrogen receptor and 93% for the progesterone receptor 8.8% of the specimens were interpreted differently. Using the Remmele score, the concordance within the group of cases, which had been interpreted as receptor-positive by both observers, was 54% for the estrogen receptor and 57% for the progesterone receptor. The Reiner score showed concordant scorings of 72% for the estrogen receptor and 79% for the progesterone receptor. The present study indicates that complete agreement between scorings of different observers may not be expected, mainly due to differences in the interpretation of the specificity of staining and of the histological structures after immunostaining. The concordance of positive results using the three-graded Reiner score is comparable to that of the three-graded Bloom and Richardson grading system of breast cancer and reflects the limitation of subjective evaluation of morphology in general.

Breast Neoplasms↗