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Karl von Smitten

Publications and source records attributed to Karl von Smitten.

13 recordsLinked to original sources
PubMed2006

Ki-67, p53, ER receptors, ploidy and S phase as long-term prognostic factors in T1 node-negative breast cancer.

BACKGROUND: The aim of the present study was to evaluate a series of biomarkers with regard to long-term prognostic value in patients with T1 (< or =2 cm) node-negative breast cancer. METHOD: The prognostic value of Ki-67, p53, oestrogen receptor (ER) immunohistochemical labelling, flow-cytometric S phase fraction and ploidy was evaluated in 212 patients with pT1N0M0 breast cancer. The median follow-up time was 15.9 years (range 0.2-27.2 years). RESULTS: In an analysis of breast cancer-specific survival up to 5 years, high Ki-67 (> or =10%; p = 0.002), high p53 (> or =20%; p = 0.01), negative ER (<30%; p = 0.01) as well as aneuploidy of the tumour (p = 0.02) were significant prognostic factors. When the follow-up was extended to 10 years, only Ki-67 (p = 0.03) was significantly associated with outcome and beyond 15 years none of the studied markers provided significant prognostic information when analyzed separately. There was a weak but significant difference in long-term survival when patients with a combination of high Ki-67 (> or =10%), high SPF (>3%) and high p53 (> or =20%) were compared to patients with other combinations (p = 0.03). CONCLUSION: According to the results of our series, it seems that several prognostic markers which are associated with short-term survival (< or =5 years) in pT1N0M0 breast cancer may not be significant predictors of long-term (>15 years) breast cancer-specific survival.

Adult↗
PubMed2006

BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition.

BARD1 (BRCA1-associated RING-domain 1) is a tumor suppressor whose protein product interacts with BRCA1, and in which rare somatic and germline mutations have been reported in breast, uterine, and endometrial cancers. We aimed to evaluate whether there are BARD1 genetic variants that contribute to breast cancer risk by screening the gene for germline alterations in 45 Finnish familial breast cancer patients and in seven patients with both breast and ovarian cancer. Two of the missense alterations identified (Cys557Ser and Val507Met) were recently suggested to associate with an increased breast cancer risk. We also analyzed these variants in large and independent series of familial and unselected breast cancer patients and healthy controls. No clearly deleterious mutations were detected in the initial mutation screening. No association of the Cys557Ser and breast cancer risk was observed as the variant was found altogether in 1.4% (16/1181) of familial and 2.2% (34/1565) of unselected breast cancer patients, and in 2.5% (27/1083) of healthy controls. The frequency of the Val-allele of the Val507Met variant was modestly higher among breast cancer patients than among healthy controls, although the difference did not reach statistical significance. No statistically significant association of the Cys557Ser or Val507Met variants with any clinicopathologic parameters was observed. These results suggest that the contribution of the BARD1 germline variants to breast cancer predisposition is very limited, and that neither Cys557Ser nor Val507Met have an effect on familial breast cancer susceptibility.

Breast Neoplasms↗
PubMed2005

Breast cancer patients with p53 Pro72 homozygous genotype have a poorer survival.

PURPOSE: The p53 R72P polymorphism has been suggested to play a role in many cancers, including breast cancer. Our aim was to evaluate association of R72P with breast cancer risk as well as histopathologic features of the breast tumors and survival. EXPERIMENTAL DESIGN: The germ line R72P genotype was defined among 939 Finnish familial and 888 unselected breast cancer patients and 736 healthy population controls. The clinical and biological variables were tested for association by univariate analysis and the effects of several variables on survival by Cox's proportional hazards regression model. RESULTS: The distribution of the genotypes was similar in all groups studied, suggesting no association with breast cancer risk. Unselected breast cancer patients with 72P homozygous genotype presented significantly more often with lobular carcinoma, whereas R72 allele carriers had a significantly higher frequency of ductal carcinomas (P = 0.004). No significant association with other histopathologic variables, like tumor grade, hormone receptor status (estrogen and progesterone receptors), or tumor-node-metastasis stage, was observed. Survival analysis showed that unselected breast cancer patients with 72P homozygous genotype had significantly poorer survival than patients with other genotypes (P = 0.003). This effect on survival was independent of p53 expression in the tumors and multivariate analysis showed that 72P homozygous genotype was overall an independent prognostic factor (risk ratio of death, 2.1; 95% confidence interval, 1.4-3.3; P = 0.001). CONCLUSIONS: These results suggest no effect of either R72P allele on breast cancer risk but a significantly reduced survival for 72P homozygous breast cancer patients. The finding of codon 72 genotype as an independent prognostic marker for breast cancer warrants further studies.

Biomarkers, Tumor↗
PubMed2005

Human breast cancer in vitro: matching histo-pathology with small-angle x-ray scattering and diffraction enhanced x-ray imaging.

Twenty-eight human breast tumour specimens were studied with small-angle x-ray scattering (SAXS), and 10 of those were imaged by the diffraction enhanced x-ray imaging (DEI) technique. The sample diameter was 20 mm and the thickness 1 mm. Two examples of ductal carcinoma are illustrated by histology images, DEI, and maps of the collagen d-spacing and scattered intensity in the Porod regime, which characterize the SAXS patterns from collagen-rich regions of the samples. Histo-pathology reveals the cancer-invaded regions, and the maps of the SAXS parameters show that in these regions the scattering signal differs significantly from scattering by the surrounding tissue, indicating a degradation of the collagen structure in the invaded regions. The DEI images show the borders between collagen and adipose tissue and provide a co-ordinate system for tissue mapping by SAXS. In addition, degradation of the collagen structure in an invaded region is revealed by fading contrast of the DEI refraction image. The 28 samples include fresh, defrosted tissue and formalin-fixed tissue. The d-values with their standard deviations are given. In the fresh samples there is a systematic 0.76% increase of the d-value in the invaded regions, averaged over 11 samples. Only intra-sample comparisons are made for the formalin-fixed samples, and with a long fixation time, the difference in the d-value stabilizes at about 0.7%. The correspondence between the DEI images, the SAXS maps and the histo-pathology suggests that definitive information on tumour growth and malignancy is obtained by combining these x-ray methods.

Breast Neoplasms↗
PubMed2005

Quantitative comparison between two phase contrast techniques: diffraction enhanced imaging and phase propagation imaging.

Two x-ray phase contrast imaging techniques are compared in a quantitative way for future mammographic applications: diffraction enhanced imaging (DEI) and phase propagation imaging (PPI). DEI involves, downstream of the sample, an analyser crystal acting as an angular filter for x-rays refracted by the sample. PPI simply uses the propagation (Fresnel diffraction) of the monochromatic and partially coherent x-ray beam over large distances. The information given by the two techniques is assessed by theoretical simulations and compared at the level of the experimental results for different kinds of samples (phantoms and real tissues). The imaging parameters such as the energy, the angular position of the analyser crystal in the DEI case or the sample to detector distance in the PPI case were varied in order to optimize the image quality in terms of contrast, visibility and figure of merit.

Breast Neoplasms↗
PubMed2004

Radio-guided occult lesion localization in patients undergoing breast-conserving surgery and sentinel node biopsy.

BACKGROUND: The objective of the study was to evaluate the feasibility of radio-guided occult lesion localization (ROLL) in breast-conserving surgery for nonpalpable breast cancer. METHODS: Altogether 215 breast cancer patients were included in a prospective study. Ultrasonographically guided intratumoral injection of radioactive tracer was used for tumor localization in 64 patients with nonpalpable tumors, visible in breast ultrasonography (the ROLL group). Nonpalpable tumors, visible only in mammography, were localized with a help of a guidewire in 14 patients (the WGR group). The remaining 137 patients had palpable tumors. RESULTS: The proportion of specimens with close or involved margins (0 to 3 mm) was the same in the ROLL group (6%) and among cases with palpable tumors (5%). In addition the median length of the closest margin did not differ significantly between the groups. CONCLUSIONS: The results of ROLL for nonpalpable breast cancer are comparable with those for resection of palpable tumors.

Adult↗
PubMed2004

Reinnervation of arterial grafts by adrenergic nerves occurs in rats as indicated by increased levels of noradrenaline.

To investigate the changes in noradrenaline concentrations in transplanted arterial grafts in rats, 31 female rats 4 to 6 weeks old of the AO/Ks:OC strain were operated on. Femoral arterial grafts were anastomosed to carotid arteries and compared with control femoral segments. Six rats were included in each follow-up group at 0, 1, 4, and 12 weeks, and there were seven rats in the 20-week follow-up group. High-performance liquid chromatography was used to determine the concentrations of noradrenaline. The operation itself decreased noradrenaline concentrations in the grafts to 76 percent of that in the control segments. One week after the operation, the noradrenaline concentration had fallen to 1.7 percent of the control values and started to recover thereafter. One month after the operation, it was 23 percent; at 3 months, it was 31 percent; and at 5 months, it was 43 percent of control values. The decrease from time 0 to 1 week was significant (p = 0.001), as was the increase from 1 week to 20 weeks (p = 0.004). Noradrenaline concentrations had fallen significantly 1 week after the operation and thereafter they increased to levels comparable to those seen in the immediate postoperative period.

Adrenergic Fibers↗
PubMed2003

Motion restriction and axillary web syndrome after sentinel node biopsy and axillary clearance in breast cancer.

BACKGROUND: We evaluated the prevalence of motion restriction and axillary web syndrome (AWS) after sentinel node biopsy (SNB) and axillary clearance (AC) in a prospective study. AWS is a self-limiting cause of early postoperative morbidity after axillary surgery. Limited range of motion associated with palpable cords of tissue in the axilla are typical for AWS. METHODS: Altogether 85 breast cancer patients who underwent SNB only (49 patients) or SNB and AC (36 patients) were examined before and after surgery. The range of shoulder flexion and abduction and the presence of AWS were registered. RESULTS: The range of shoulder movements was restricted in 24 (45%) patients after SNB only and in 31 (86%) patients who also underwent AC (P = 0.002). AWS was encountered in 10 (20%) patients with SNB and in 26 (72%) with AC (P <0.00005). CONCLUSIONS: In the SNB group, significantly less early postoperative morbidity was observed.

Adult↗
PubMed2003

Predictive factors for the status of non-sentinel nodes in breast cancer patients with tumor positive sentinel nodes.

In patients with tumor positive sentinel nodes, axillary lymph node dissection is routinely performed while a majority of these patients have no tumor involvement in the non-sentinel nodes. The authors tried to identify a subgroup of patients with a tumor positive sentinel node without non-sentinel node tumor involvement. In 135 consecutive patients with tumor positive sentinel nodes and axillary lymph node dissection performed, the incidence of non-sentinel node involvement according to tumor and sentinel node related factors was examined. The size of the sentinel node metastasis, size of primary tumor and number of tumor positive sentinel nodes were the three factors significantly predicting the status of the non-sentinel nodes. The size of the sentinel node metastasis was the strongest predictive factor (P < 0.0001). In a subgroup of 41 patients with a stage T1 tumor and micrometastatic involvement in the sentinel node only 2 patients (5%) had non-sentinel node involvement. In patients with small primary tumors and micrometastatic involvement of the sentinel nodes, the chance of non-sentinel node involvement is small but cannot be discarded. Because the clinical relevance of micrometastases in lymph nodes is still unclear it is not advisable to omit axillary lymph node dissection even in these patients.

Adult↗
PubMed2003

Prophylactic mastectomy: why and when?

Introduction of BRCA1 and BRCA2 gene mutation analysis has increased interest in prophylactic mastectomy and immediate breast reconstruction as a risk reduction measure for women at increased risk of breast cancer. Prophylactic mastectomy has been suggested to decrease the risk of breast cancer by at least 90%. Because the cosmetic result of immediate breast reconstruction may not be optimal, nipple sensation is lost, and capsule contraction may cause problems when silicon prostheses are used, the patients should be well informed of risks and other preventive methods. Surveillance or chemoprevention are suggested as alternatives to risk reduction mastectomy, but there is lack of prospective randomised trials comparing these options. Because BRCA1 and BRCA2 gene mutations also increase risk of ovarian cancer, management of these patients should be shared by the breast surgeon and gynaecologist.

Adult↗
PubMed2003

Amplification of erbB2 and erbB2 expression are superior to estrogen receptor status as risk factors for distant recurrence in pT1N0M0 breast cancer: a nationwide population-based study.

PURPOSE: To assess the relative importance of 10 prognostic factors in pT1N0M0 breast cancer (< or =2 cm in diameter, node negative). EXPERIMENTAL DESIGN: Women diagnosed with breast cancer in Finland from 1991 to 1992 were identified from the files of the Finnish Cancer Registry, and individual clinicopathological data were collected from the hospital case records of women living in five regions comprising about one-half of the Finnish population. Of the women with minimum required information available (n = 2842), 852 had unilateral pT(1)N(0)M(0) cancer. The median follow-up time was 9.5 years, and only 5% had received systemic adjuvant therapy. Estrogen receptor (ER), progesterone receptor, erbB2, p53, and Ki-67 expression was determined from tumor tissue microarrays using immunohistochemistry, and the erbB2 (HER-2) amplification status was determined using chromogenic in situ hybridization. RESULTS: Primary tumor size < or =5 mm and histological grade 1 were associated with 100 and 95% (95% confidence interval, 92-98%) 9-year distant disease-free survival, respectively, whereas strong erbB2 expression or the presence of >20% Ki-67-positive cells was associated with >20% risk. ER and progesterone receptor values obtained from the hospital case records or tumor microarrays showed weaker association with outcome than the erbB2 status. Small (< or =10 mm) erbB2-negative cancers were associated with >90% 9-year distant disease-free survival, irrespective of histological grade. CONCLUSIONS: Prognosis of pT(1)N(0)M(0) breast cancer is generally well defined by the histological grade and primary tumor size. The erbB2 status was superior to ER as a prognostic factor in these tumors.

Adult↗
PubMedDate not supplied

Accuracy of axillary staging using sentinel node biopsy or diagnostic axillary lymph node dissection--a case-control study.

We aimed to compare the accuracy of axillary staging in breast cancer between sentinel node biopsy (SNB) and axillary lymph node dissection (ALND). The prevalence of axillary metastases was studied in 166 breast cancer patients with SNB and pair-matched control patients with ALND. The matching factors included age of the patient and grade, histological type and histological size of the tumour. There were 37% of patients with axillary metastases in the SNB group and 31% in the ALND group. Altogether, 57 pairs were discordant in relation to axillary metastases. In 34 discordant pairs the SNB patient and in 23 the ALND patient had axillary metastases, p=ns. Among the 36 discordant pairs with invasive ductal carcinoma (IDC), axillary metastases were detected as often in the SNB and the ALND patients. In the 21 discordant pairs with other histological types, the SNB patient had axillary metastases in 16 pairs and the ALND patient in 5 pairs, p<0.03. SNB seems to be as accurate a method for axillary staging as ALND. However, SNB generated no upstaging effect in IDC, only in other histological tumour types.

Adult↗