PubMed Health⌕ Search

Biomedical subjects

T Sauer

Publications and source records attributed to T Sauer.

At least 19 recordsLinked to original sources

Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer.

PURPOSE: This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer. PATIENTS AND METHODS: BM aspirates were collected from 817 patients at primary surgery. Tumor cells in BM were detected by immunocytochemistry using anticytokeratin antibodies (AE1/AE3). Analyses of the primary tumor included histologic grading, vascular invasion, and immunohistochemical detection of c-erbB-2, cathepsin D, p53, and estrogen receptor (ER)/progesterone receptor (PgR) expression. These analyses were compared with clinical outcome. The median follow-up was 49 months. RESULTS: ITC were detected in 13.2% of the patients. The detection rate rose with increasing tumor size (P =.011) and lymph node involvement (P <.001). Systemic relapse and death from breast cancer occurred in 31.7% and 26.9% of the BM-positive patients versus 13.7% and 10.9% of BM-negative patients, respectively (P <.001). Analyzing node-positive and node-negative patients separately, ITC positivity was associated with poor prognosis in the node-positive group and in node-negative patients not receiving adjuvant therapy (T1N0). In multivariate analysis, ITC in BM was an independent prognostic factor together with node, tumor, and ER/PgR status, histologic grade, and vascular invasion. In separate analysis of the T1N0 patients, histologic grade was independently associated with both distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS), ITC detection was associated with BCSS, and vascular invasion was associated with DDFS. CONCLUSION: ITC in BM is an independent predictor of DDFS and BCSS. An unfavorable prognosis was observed for node-positive patients and for node-negative patients not receiving systemic therapy. A combination of several independent prognostic factors can classify subgroups of patients into excellent and high-risk prognosis groups.

Biopsy, Needle↗

Logistics of referral, diagnostic assessment and treatment of patients with breast symptoms and signs.

BACKGROUND AND AIMS: The logistics of diagnosis and treatment in a hospital with slightly above 400 new cases of breast cancer per year is analysed. MATERIALS AND METHODS: The patient flow from referral, through the diagnostic procedures and through surgical treatment is described. RESULTS AND CONCLUSIONS: The basic principle of the diagnostic assessment is the triple diagnostic procedure including mammography supplemented by ultrasonography, fine needle aspiration cytology and clinical examination. The radiologist and pathologist are working together in the breast diagnostic centre and are thus able to give a "single visit diagnosis" in most cases. The surgeon sees the patient either the same day or the next. A "consensus meeting" held each week with representatives for all specialities present has an important function in quality assurance and education. If one or more of the triple diagnostic components reach conclusion level "suspicious lesion", surgery is indicated. In hospital management is based on day surgery for all biopsies, wide excisions with or without sentinel node and some ablatio simplex mammae. For wide excision and ablation with complete axillary node clearance, the patients are transferred from the day surgery unit to a patient hotel after 3-4 hours of observation and stay till the drain can be removed. Only in rare case of high cardiopulmonary risk, beds in ordinary wards are used. This is a highly cost efficient logistic saving the hospital approximately 400,000 EUR a year compared to ordinary in hospital treatment.

Breast Neoplasms↗

Immunocytochemical expression of E-cadherin on fine-needle aspirates from breast carcinomas correlate with the cell dissociation pattern seen on smears.

Altered E-cadherin expression has been suggested to be of prognostic significance in breast cancers and to correlate with tumor subtype and grade. A dysfunctional, intercellular adhesion system may be responsible for the tumor cell dissociation pattern seen on fine-needle aspirate cytology (FNAC). The aim of our study was to determine E-cadherin expression on direct FNAC smears from breast carcinomas and compare the results with the dyscohesion grade of the tumor cells and the cytological grading. The material consisted of FNAs from 56 breast carcinomas. The degree of cellular cohesion was estimated semiquantitatively. Full expression of E-cadherin was defined as a complete and strong membrane staining of virtually all tumor cells. All nonductal as well as 85% of the invasive ductal carcinomas revealed reduced expression or negativity for E-cadherin. In all, 25% of carcinomas with dyscohesion Grade 1 (mainly in groups) revealed full expression of E-cadherin, in contrast to 12.5% of tumors with dyscohesion Grade 3 (mainly dispersed cells). Nuclear positivity was seen in 21% of the tumors (12 cases) and seven of these were G3 ductal carcinomas. In conclusion, E-cadherin expression correlated with the cell dissociation pattern seen on direct smears from FNAC of breast carcinomas, but is only one of several markers that modulate this pattern. High-grade carcinomas rarely revealed full expression and had a high incidence of aberrant nuclear localization of E-cadherin.

Biopsy, Needle↗

Early seizure detection.

For patients with medically intractable epilepsy, there have been few effective alternatives to resective surgery, a destructive, irreversible treatment. A strategy receiving increased attention is using interictal spike patterns and continuous EEG measurements from epileptic patients to predict and ultimately control seizure activity via chemical or electrical control systems. This work compares results of seven linear and nonlinear methods (analysis of power spectra, cross-correlation, principal components, phase, wavelets, correlation integral, and mutual prediction) in detecting the earliest dynamical changes preceding 12 intracranially-recorded seizures from 4 patients. A method of counting standard deviations was used to compare across methods, and the earliest departures from thresholds determined from non-seizure EEG were compared to a neurologist's judgement. For these data, the nonlinear methods offered no predictive advantage over the linear methods. All the methods described here were successful in detecting changes leading to a seizure between one and two minutes before the first changes noted by the neurologist, although analysis of phase correlation proved the most robust. The success of phase analysis may be due in part to its complete insensitivity to amplitude, which may provide a significant source of error.

Brain Mapping↗

Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics.

UNLABELLED: PURPOSE/EXPERIMENTAL DESIGN: The importance of detection of disseminated isolated tumor cells (ITCs) in bone marrow (BM) is still not settled. BM aspirates from 920 patients with primary breast cancer were analyzed for tumor cells by standardized direct immunocytochemical analysis (ICC) of 2 x 10(6) mononuclear cells (MNCs) using anticytokeratin monoclonal antibody (AE1/AE3). Samples (637) were analyzed by negative immunomagnetic enrichment (IMS) followed by ICC (10 x 10(6) MNCs). Analyses of the primary tumor specimens have been performed, including histomorphology, tumor-node-metastasis (TNM) staging, grading, and immunohistochemical analyses. RESULTS: Of the patients with infiltrating carcinoma, 63% were node negative (N0) and 33%, node positive (N+). The results show the presence of tumor cells in 13.4% of the evaluable patients after direct ICC analysis. The presence of tumor cells correlated to the nodal- and tumor stage, showing BM positivity in 9.9% of the N0 cases and 20.6% in the N+ group (P < 0.0005), 11.2% of the stage T(1) were positive, and 15.0% and 22.6% were positive in the T(2) and T(3/4) groups, respectively (P = 0.013). No correlation between detection of ITC and detection of p53 and cathepsin D expression was found. Vascular invasion and c-erbB2 expression were associated with ITCs in BM (P = 0.045 and P = 0.024, respectively). Node-negative patients with estrogen receptor (ER)+ and/or progesterone receptor (PgR)+ tumors had lower frequency of ITCs than ER-/PgR- (P = 0.004). The use of negative IMS increased the frequency of positive BM by 63% (P < 0.0005). CONCLUSIONS: The direct ICC detection of ITCs in BM correlated with primary tumor stage, nodal stage, vascular invasion, c-erbB2 expression, and ER/PgR status. Analysis of larger BM samples by negative IMS resulted in increased number of ITC-positive patients.

Antibodies, Monoclonal↗

[Diagnostic and therapeutic localized breast biopsy].

Preoperative localized mammary biopsy has been used as a diagnostic tool since before 1983 in the Breast Clinic, Ullevål Hospital. The great majority of procedures have been performed in the outpatient clinic with use of local anesthesia. Since 1988 all activity has been registered prospectively in a database. We discuss the use of the procedure and the results obtained during the period 1983-95. In the later part of the observed period, the use of the procedure as a diagnostic tool has been less frequent, but it has been increasingly used as a tool to identify the pathologic process when performing breast-conserving surgery. Surveillance of the malign-benign ratio is an important parameter in the quality assurance of the procedure. The malign-benign ratio has been greater than 0.3 during the period of observation. Continuous registration of procedure-related parameters is necessary for documentation of the results.

Biopsy, Needle↗

Endothelial cell autoantibodies are a marker of disease susceptibility in inflammatory bowel disease but apparently not linked to persistent measles virus infection.

Intestinal vasculitis caused by persistent measles virus infection of intestinal endothelial cells was described in Crohn's disease. Furthermore, endothelial cell autoantibodies have been demonstrated in inflammatory bowel disease (IBD). Autoantibodies against intestinal endothelial cells were visualized by indirect immunofluorescence in patients with IBD, in their healthy first-degree relatives, in patients with infectious enterocolitis, and in healthy, unrelated controls. In intestinal tissue specimens of 22 antibody-positive IBD patients a search for the measles virus genome was performed. Endothelial cell autoantibodies were significantly more frequent in patients with IBD, in both groups of first-degree relatives, and in patients with infectious enterocolitis than in the healthy controls (P = 0.0002 or less). The measles virus genome was found in none of the intestinal biopsies. Endothelial cell autoantibodies are not a genetic but rather an epigenetic (infectious) marker of disease susceptibility. The expression of these autoantibodies is unlikely to be triggered by a persistent measles virus infection.

Adolescent↗

Cell cycle dependence of gene transfer by lipoplex, polyplex and recombinant adenovirus.

The aim of this study was to investigate the influence of cell cycle on transfection efficiency. Counterflow centrifugal elutriation was used which avoids possible side-effects from chemical treatment of cells. With this method, cell populations were fractionated by means of size and density, and fractions corresponding to discrete cell cycle phase-specific populations were transfected with various nonviral methods (Lipofectamine, TfpLys and TfPEI), adenovirus-enhanced transferrinfection (AVET system) and recombinant adenovirus. Transfection efficiency was found to be strongly dependent on the cell cycle stage at the time of transfection. Luciferase activity from cells transfected with polycation- or lipid-based transfection systems was 30- to more than 500-fold higher when transfection was performed during S or G2 phase compared with cells in G1 phase which have the lowest expression levels. In contrast, this effect was not observed with recombinant adenovirus which varied only four-fold. Our results indicate that mitotic activity enhances transfection not only by lipoplexes but also by polyplexes, but not a viral system which has an efficient nuclear entry machinery, suggesting that transfection close to M phase is facilitated perhaps by nuclear membrane breakdown. Furthermore, low transfection success into G1 cells indicates that DNA complexes deposited in G1 cells are probably not retained long enough to take advantage of mitosis effects or that passage of transfected cells through S phase is inhibitory. Gene Therapy (2000) 7, 401-407.

Adenoviridae↗

Physicochemical analysis of purified diphtheria toxoids: is toxoided then purified the same as purified then toxoided?

Diphtheria toxin can be converted into a highly immunogenic and irreversibly detoxified vaccine either using the conventional process in which the crude toxin is formalinised and subsequently purified (DTxd(conv)) or by detoxification of the highly purified toxin (DTxd(new)). In this study, both DTxd(new) and DTxd(conv) were evaluated by use of physico-chemical methods. For some methods, results were also compared to those obtained for cross-reacting material (CRM197), which is a non-toxic mutant of diphtheria toxin. DTxd(new) was assayed to have a specific purity of at least 2300 LF/mg protein N, thereby exceeding Pharm. Eur. requirements by up to 35%. Superior purity of DTxd(new) could also be demonstrated by size exclusion HPLC experiments and by amino acid composition studies. Far-UV circular dichroism spectroscopy revealed that the secondary structure of DTxd(new) almost resembled that of CRM197, suggesting only minor molecular changes during detoxification. This study worked out differences between purified diphtheria toxoids. Physico-chemical means revealed the advantages of DTxd(new) being the purer and more defined product, thus making it highly efficient for its use as a vaccine carrier as well as a component of vaccine combinations.

Amino Acids↗

[A prospective registration of diagnosis and treatment of breast tumors at the Ulleval hospital 1988-1995].

During the years 1988 to 1995, all diagnostic and therapeutic activities in the Breast Clinic, Ullevål Hospital, Oslo, Norway were registered prospectively. This paper presents the results from the registration. Of 4,436 new referrals, 1,169 had infiltrating mammary carcinoma and 63 ductal carcinoma in situ. 13.6% of those with breast carcinoma and 12.3% of those with benign breast disease had a first degree relative with breast cancer. The use of diagnostic biopsies for palpable and nonpalpable lesions decreased significantly through the period, from 155/112 in 1988 to 65/78 in 1995. For palpable lesions, the malign/benign ratio decreased from 0.82 in 1988 to 0.54 in 1995 while it improved from 0.43 to 0.88 for marked biopsies for nonpalpable lesions. Excluding those with mammographically and/or cytologically suspicious lesions from those who had a biopsy for a palpable lesion, we found that only seven out of 101 had cancer (ratio 0.07). Radical surgery was done in 790 cases with cytology as the only pre- and peroperative cancer verification. Three of them had a false positive cytology, as cancer was not found in the breast. One patient had metastasis later confirming that a cancer had been present; thus we had two false positive cytologies (2.5 per thousand). More than six axillary lymph nodes have to be examined in order to avoid false negative axillary status. In 1988 we had 41% with less than six nodes examined. This improved to 15% in 1995. Breast preserving therapy increased throughout the period from 4.1% in 1988 to 29.4% in 1995. Tumor size (pTI around 40%) and node positivity (35%) was fairly constant. In our opinion, a continuous prospective registration of the activity in a breast diagnostic centre is essential in order to improve and maintain service quality. The decision made by the Norwegian parliament in 1998 to introduce nation-wide mammography screening may be used to institute such continuous prospective registrations in all centres involved in the screening.

Breast Neoplasms↗

Estimating loss of the wild-type p53 gene by in situ hybridization of fine-needle aspirates from breast carcinomas.

TP53 mutations have been found in 16-64% of breast carcinomas. The aim of our study was to investigate loss of the wild-type TP53 gene by in situ hybridization (ISH) of fine-needle aspirates (FNAC) from breast carcinomas. The material consisted of FNAC from 33 breast carcinomas, with histologic specimens from 19 of the cases. Routine diagnostic smears were used for cytologic grading. ISH of the wild-type TP53 gene and chromosome 17 was performed on air-dried smears. Hybridization signals were counted in at least 100 nuclei, and the percentage for each signal number was calculated. FNAC from four fibroadenomas as well as cell preparations from five lymphocyte cultures were used as normal/benign controls. Cutoff for defining loss of p53 gene signals was set at 20% of cells with zero and one gene signal only. Concomitant p53 protein expression was determined on 20 histologic sections and eight additionally available air-dried smears. Loss of wild-type p53 gene was found in 20 carcinomas (60.6%). The rate of signal loss varied from 0.4% to 75.3% of the cells. All tumors with aneusomy of chromosome 17 revealed loss of p53 gene signals, as did 42% of the disome cases. Loss of wild-type p53 gene was present in 10 of 16 grade 1 cancers (62.5%), eight of 13 grade 2 tumors (61.5%), and two of four grade 3 cases. Signal loss did not correlate with p53 protein expression. In conclusion, subpopulations with loss of the wild-type p53 gene are a common finding in breast carcinomas; they are detected in more than 60% of the tumors, including grade 1 cancers.

Biopsy, Needle↗

Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count.

OBJECTIVE: To determine the aetiology and clinical significance of an elevated platelet count (thrombocytosis) in a large cohort of patients. DESIGN: A retrospective review of the medical records was performed on all patients, who had at least one platelet count > or = 500 x 10(9) L-1. SETTING: Departments of Medicine and Surgery, University of Ulm, Germany. SUBJECTS: A total of 732 patients with thrombocytosis. MAIN OUTCOME MEASURES: Classification of thrombocytosis and thromboembolic complications, and evaluation of laboratory parameters distinguishing between primary and secondary thrombocytosis. RESULTS: Of the total of 732 patients, 89 (12.3%) had primary and 643 (87.7%) had secondary thrombocytosis. Essential thrombocythaemia was observed in 40 of 89 patients (45%) with primary thrombocytosis. The most frequent causes of secondary thrombocytosis were tissue damage (42%), infection (24%), malignancy (13%) and chronic inflammation (10%). Primary thrombocytosis was significantly associated with a higher platelet count and an increased incidence of both arterial and venous thromboembolic complications. In secondary thrombocytosis, thromboembolic events were restricted to the venous system and occurred only in the presence of other risk factors. Mean values of leucocyte count, haematocrit, erythrocyte sedimentation rate, fibrinogen, serum potassium and lactate dehydrogenase were significantly different in primary and secondary thrombocytosis. CONCLUSIONS: The finding of an elevated platelet count on routine blood examination has diagnostic, prognostic and therapeutic implications. It is of clinical importance to distinguish between primary and secondary thrombocytosis, as thrombotic complications occur more frequently in primary thrombocytosis. Unless additional risk factors are present, secondary thrombocytosis is not associated with a significant risk for thromboembolic events.

Adolescent↗

Numerical abnormalities of chromosome 7 in interphase cell nuclei of breast carcinoma have no impact on immunohistochemically determined EGFR status.

AIM OF STUDY: To investigate the relationship between epidermal growth factor receptor (EGFR) status and numerical aberrations of chromosome 7 in breast carcinomas. DESIGN: In situ hybridization (ISH) of interphase cell nuclei on air-dried fine-needle aspirates (FNAC) from 33 breast carcinomas was evaluated for numerical abnormalities in chromosome 6, 7, 12 and 17. Immunohistochemical staining of EGFR was performed on corresponding histological specimens. RESULTS: 78% of the tumours were aneuploid by ISH. Aneusomy of chromosome 7 was found in 18 cases (60%). EGFR overexpression was observed in 30% of the carcinomas, and seven of nine were aneuploid by ISH. The same percentage of chromosome 7 aneusomy was found in both EGFR-positive and -negative cases. Five of seven EGFR-positive tumours revealed aneusomy of chromosome 7. CONCLUSION: Numerical gain of chromosome 7 is a common finding, occurring in about 60% of breast carcinomas. Most EGFR-positive tumours are aneuploid and show numerical gain of chromosome 7, but abnormal numbers of chromosome 7 have no impact on the EGFR status.

Breast Neoplasms↗

Ultrasonography of malignant breast neoplasms. Analysis of carcinomas missed as tumor.

PURPOSE: To analyze the malignant breast neoplasms missed as tumor on ultrasonography (US). MATERIAL AND METHODS: A total of 355 malignant tumors were confirmed at histology among 2,985 consecutive patients who underwent breast US. There were no prospectively recorded mammographic findings in 28 of the 355 tumors. The remaining 327 tumors included 16 ductal carcinomas in situ (DCIS) and 66 invasive carcinomas with suspicious microcalcifications on mammography. Excluding these 82 tumors because US would not have been indicated using strict criteria, a subpopulation of 245 noncalcified invasive malignant tumors remained for analysis. The neoplasms missed as tumor on US were analyzed for the whole tumor group (n=355) and the subpopulation (n=245). RESULTS: 42 (11.8%) of the 355 malignant neoplasms were missed as tumor on US, including 6 (2.5%) of the 243 palpable and 36 (32.1%) of the 1 12 nonpalpable malignancies. Most of the missed tumors were DCIS and microinvasive ductal carcinomas dominated by DCIS. In the subpopulation, 14 (5.7%) of the 245 malignancies were missed as tumor on US, including 4 (2.2%) of the 180 palpable and 10 (15.4%) of the 65 nonpalpable lesions. Of the 245 malignancies, 6 (2.4%) had a normal US finding, including 2 palpable retropapillary tumors and 4 incidental findings at histology. CONCLUSION: Using strict criteria for performing US as an adjunct to mammography, by far the most malignant breast neoplasms are diagnosed as a tumor on US.

Adolescent↗

[Breast conserving surgery for breast cancer--local recurrence].

One of the disadvantages of breast conserving treatment compared with mastectomy is the higher rate of local recurrence. Even though a local recurrence has no influence on survival, it is a psychological trauma for the woman it affects. Breast conserving treatment has been practised at Ullevaal Hospital since 1986. This study is based on data from 216 consecutive cases of breast conserving surgery, from January 1986 to March 1996. Mean observation time was 29 months. Nine (4.2%) patients experienced a local recurrence. Age, histological grade, and the size of the tumor were identified as risk factors, whereas there was no correlation between histology, axillary node involvement, and surgical margins.

Adult↗

nm23 protein expression in fine-needle aspirates from breast carcinoma: inverse correlation with cytologic grading, lymph node status, and ploidy.

BACKGROUND: nm23 has been recognized as a potential suppressor gene of metastasis. Reduced nm23 expression in breast carcinoma has been found to correlate with axillary lymph node metastases, high grade tumors, and shorter survival. METHODS: nm23 protein was detected immunocytochemically using an avidin-biotin complex technique. When a few cells showed negative or marked reduced cytoplasmic staining, expression was considered reduced. Cytologic grading was performed on routine fine-needle aspirates (FNAC). Ploidy was determined by in situ hybridization of chromosomes 6, 7, 12, and 17 on interphase cell nuclei from FNAC. When all four chromosomes revealed a disome pattern, the tumor was classified as diploid; mixed disome/aneusome carcinomas as well as those with aneusomy in all four chromosomes were considered aneuploid. RESULTS: Approximately 83% of specimens had reduced expression of nm23 protein. Forty-four of 45 lymph node positive tumors as well as 27 of 29 aneuploid tumors, were found to have reduced nm23 expression. Likewise, 49 of 57 Grade 2 (G2) carcinomas (86%) and 20 of 22 Grade 3 (G3) carcinomas (91%) showed reduced nm23 expression. Twenty-nine of 39 Grade 1 (G1) carcinomas (74%) had reduced nm23 expression. None of the G1 or G2 tumors with full nm23 expression had axillary lymph node metastases. CONCLUSIONS: nm23 protein showed a significant inverse correlation with lymph node status, cytologic grading, and ploidy. The nm23 protein antibody may have potential as a preoperative marker in identifying subgroups of patients who either may have a worse prognosis than expected (e.g., those with G1 carcinomas with reduced nm23 expression) or who may be able to avoid axillary lymph node dissection (e.g., those with G1 carcinoma with full nm23 protein expression). Cancer

Biomarkers, Tumor↗

An increased risk of cervical intra-epithelial neoplasia grade II-III among human papillomavirus positive patients with the HLA-DQA1*0102-DQB1*0602 haplotype: a population-based case-control study of Norwegian women.

Several recent studies have reported different associations between HLA specificities and human papillomavirus (HPV)-associated disease of the cervix. We report the distribution of DQA1 and DQB1 genes and HPV infection in a population-based case-control study including 92 patients with histologically verified cervical intraepithelial neoplasia grade II-III (CIN II-III) (thus including moderate and severe dysplasia and carcinoma in situ) and 225 control subjects. We found an overrepresentation of the DQA1*0102-DQB1*0602 haplotype among HPV-positive cases compared with controls. The association was even stronger when comparing HPV-16-positive cases with HPV-16-positive controls. In addition, among HPV-16-positive individuals, we observed a decreased frequency of DQA1*0102-DQB1*0604 in cases compared with controls. We were not able to detect any association between CIN II-III and DQB1*03. Compared with previous findings in cervical cancer, our data indicate that carrying the DQA1*0102-DQB1*0602 haplotype gives an increased risk of developing CIN when infected with HPV-16, without influencing progression to cancer.

Adult↗