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For classification of breast cancer (BC), tumor-node-metastasis (TNM) staging has been considered state of the art for more than 50 years. The T category is well defined, and in multicentric and multifocal tumors, tumor size is assessed by the largest tumor focus. The aim of this study was to compare multicentric/multifocal tumor spread in breast cancer with unifocal disease and to evaluate the diagnostic relevance of multifocality. A retrospective analysis was performed on survival related events in a series of 5,691 breast cancer patients between 1963 and 2007. By matched-pair analysis, patients were entered into two comparable groups of 288 patients after categorizing them as having multifocal/multicentric or unifocal breast cancers. Matching criteria were tumor size, grading, and hormone receptor status, which were equally distributed between both groups (P = 1.000 each). Disease free survival and the occurrence of relapse or of metastatic disease were evaluated. Cox's regression analysis was used for multivariate analysis. In the unifocal group, the mean breast cancer-specific survival time was 221.6 months as opposed to 203.3 months in the multicentric/multifocal group (P < 0.001, log-rank test). The occurrence of local relapse and distant metastasis was significantly increased in the multifocal group in comparison to the unifocal equivalent group (P < 0.001 and P < 0.003, respectively). Cox regression analysis for multivariate analyses demonstrated focality and centricity to be highly significant predictors for reduced overall survival (P = 0.016), local relapse (P = 0.001) and distant metastasis (P = 0.038). Tumor size, histopathological grading, hormone receptor status, and staging of lymph nodes are well-established prognostic parameters. Additionally, the number of foci should be considered as an independent prognostic parameter, which is currently not reflected in the TNM classification. We conclude that multicentric/multifocal BC is an independent BC risk factor and should be included in the risk assessment by re-evaluating the current TNM classification of the UICC.

BackgroundCirculating tumor cells (CTC) in the peripheral blood in women with breast cancer has been found to be an indicator of prognosis before the start of systemic treatment. The aim of this study is the assessment of specific cytokine profiles as markers for CTC involvement that could act as independent prognostic markers in terms of survival outcome for breast cancer patients.MethodsPatients selected for this study were defined as women with breast cancer of the SUCCESS study. A total of 200 patients’ sera were included in this study, 100 patients being positive for circulating tumor cells (CTC) and 100 patients being CTC negative. The matching criteria were histo-pathological grading, lymph node metastasis, hormone receptor status, TNM classification, and patient survival. Commercial ELISA with a multi cytokine/chemokine array was used to screen the sera for Interleukin 15 (IL-15) and eotaxin. ResultsStatistically significant concentrations were exposed for IL-15 levels regardless of the CTC-Status, lymph node involvement, or hormone receptor status. Significantly enhanced serum IL-15 concentrations were observed in those patients with worse overall survival (OS) and disease-free survival (DFS). Elevated serum concentrations of IL-15 significantly correlate with patients diagnosed with Grade 3 tumor and worse OS. In contrast, patients with a Grade 3 tumor with a favourable OS and DFS demonstrated significantly decreased IL-15 values. The CTC negative patient subgroup with a favourable OS and DFS, showed statistically significant elevated eotaxin values.ConclusionThese findings suggest a potential functional interaction of increased IL-15 concentrations in the peripheral blood of patients with a worse OS and DFS, regardless of prognostic factors at primary diagnosis. The increased levels of the chemokine eotaxin in CTC negative patients and a favourable OS and DFS, on the other hand, suggest that the overexpression inhibits CTCs entering the peripheral blood, thus emphasizing a significant inhibition of circulation specific metastasis. To sum up, IL-15 could be used as an independent prognostic marker in terms of survival outcome for breast cancer patients and used as an early indicator to highlight high-risk patients and consequently the adjustment of cancer therapy strategies.

The progesterone receptor (PR) has been increasingly well described as an important mediator of the pathogenesis and progression of breast cancer. The aim of this study was to assess the role of PR status as a prognostic factor in addition to other well-established prognostic factors. Data from five independent German breast cancer centers were pooled. A total of 7,965 breast cancer patients were included for whom information about their PR status was known, as well as other patient and tumor characteristics commonly used as prognostic factors. Cox proportional hazards models were built to compare the predictive value of PR status in addition to age at diagnosis, tumor size, nodal status, grading, and estrogen receptor (ER) status. PR status significantly increased the accuracy of prognostic predictions with regard to overall survival, distant disease-free survival, and local recurrence-free survival. There were differences with regard to its prognostic value relative to subgroups such as nodal status, ER status, and grading. The prognostic value of PR status was greatest in patients with a positive nodal status, negative ER status, and low grading. The PR-status adds prognostic value in addition to ER status and should not be omitted from clinical routine testing. The significantly greater prognostic value in node-positive and high-grade tumors suggests a greater role in the progression of advanced and aggressive tumors.

Objective Chlamydia trachomatis infection is the most common bacterial sexual transmitted disease. Nearly 75% of all cases appear clinically unapparent and can cause, especially when getting chronically, infertility. Regarding pregnancy, a nationwide screening for C. trachomatis was established since April 1995. The aim of this study was to determine the percentage of tested patients throughout these 7 years to evaluate the execution of the German guidelines. Materials and methods Between 2001 and 2007, 12,865 patients were evaluated retrospectively concerning a Chlamydia trachomatis testing. Results A test was performed for chlamydial infection in 10,088 patients (78.4%). 65 pregnant patients (0.5%) out of 1,008 tested patients were positive for Chlamydia trachomatis . The part of tested patients was rising significantly from 2001 to 2007. In 2001, 68.3% pregnant patients were tested. The number of screened patients increased continuously up to 85.2% in 2007 ( p  < 0.001). The percentage of positive tested patients ranged from 0.27% in 2003 to 0.74% in 2005 (mean 0.50%). Conclusion Since 1995, a screening for Chlamydia trachomatis has to be offered to every pregnant woman according to the German guidelines. The number of tested pregnant patients was rising from 68.3 to 85.2% within the evaluated 7 years, which would be a necessary and welcome trend. Interestingly, the mean prevalence of 0.5% of positive tested patients in this analysed urban population seems to be very low. An explanation might be the usage of the point-of-care (POC) tests and its low sensitivity. Testing by nucleic acid amplification might lead to a higher detection rate. Although the awareness concerning Chlamydia trachomatis testing during pregnancy seems to have been changed over the recent years, these data are still dissatisfactory.

Introduction and hypothesis The use of synthetic mesh for prolapse and incontinence surgery is discussed controversially and in several countries is either no longer used or permissible. Previous approaches with autologous tissue did not show from a patient´s perspective convincing long-term results. As there have been repeatedly significant complications with synthetic mesh, a new approach is urgently needed. During orthopedics and trauma surgeries, tendons from the thigh have been used for decades to replace cruciate ligament. The procedure of tendon removal from the thigh is fast, easy to learn and morbidity is low. In addition, a long-term durability of the transplant ought to be expected. The objective of this investigation was to show our experience with a semitendinosus tendon instead of a mesh for genital prolapse repair. Method After the first successful attempts using such tendons in cervicosacropexy and pectopexy in patients with genital prolapse, we initiated a national multicenter study in 2020. Five German hospitals participated in order to determine the feasibility of cervicosacropexy with tendon tissue instead of mesh. Result Up until now, we have operated and observed 113 patients for at least 6 months and have seen stable results in terms of fixation of the apical compartment. The expected low morbidity at the donor site was also confirmed through subjective assessment of the patients (Knee and Osteoarthritis Outcome Score). Improvement of quality of life was confirmed after the procedure with the Short Form Health Survey 12, Version 2.0. The results of this multicenter study showed that the desired elevation of the apical compartment with tendon tissue can be achieved with low morbidity and without a synthetic mesh. Conclusion Women with uterine prolapse can be treated minimally invasively and with very low morbidity by using the semitendinosus tendon. The involvement of multiple (five) medical centers confirms that the technique is easy to learn and be transferred to other clinical centers.

Background Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated. Findings Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender. Significant differences were found in IL-4, IL-10, IL-12, TNF- alpha, GRO-alpha and MIP1-beta with respect to gestational age and in GRO-alpha regarding maternal age. Conclusion Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender but may vary with respect to maternal age and gestational age.

Introduction and hypothesisThe use of synthetic mesh for prolapse and incontinence surgery is discussed controversially and in several countries is either no longer used or permissible. Previous approaches with autologous tissue did not show from a patient´s perspective convincing long-term results. As there have been repeatedly significant complications with synthetic mesh, a new approach is urgently needed.During orthopedics and trauma surgeries, tendons from the thigh have been used for decades to replace cruciate ligament. The procedure of tendon removal from the thigh is fast, easy to learn and morbidity is low. In addition, a long-term durability of the transplant ought to be expected. The objective of this investigation was to show our experience with a semitendinosus tendon instead of a mesh for genital prolapse repair.MethodAfter the first successful attempts using such tendons in cervicosacropexy and pectopexy in patients with genital prolapse, we initiated a national multicenter study in 2020. Five German hospitals participated in order to determine the feasibility of cervicosacropexy with tendon tissue instead of mesh.ResultUp until now, we have operated and observed 113 patients for at least 6 months and have seen stable results in terms of fixation of the apical compartment. The expected low morbidity at the donor site was also confirmed through subjective assessment of the patients (Knee and Osteoarthritis Outcome Score). Improvement of quality of life was confirmed after the procedure with the Short Form Health Survey 12, Version 2.0. The results of this multicenter study showed that the desired elevation of the apical compartment with tendon tissue can be achieved with low morbidity and without a synthetic mesh.ConclusionWomen with uterine prolapse can be treated minimally invasively and with very low morbidity by using the semitendinosus tendon. The involvement of multiple (five) medical centers confirms that the technique is easy to learn and be transferred to other clinical centers.

Introduction Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear. Methods This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0–29.9), slightly obese (BMI 30.0–34.9), moderately obese (BMI 35.0–39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors. Results Multivariate analyses revealed an independent prognostic effect of BMI on DFS ( p  = 0.001) and OS ( p  = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71–4.28, p  < 0.001) and OS (HR 2.79, 95 % CI 1.63–4.77, p  < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes. Conclusions Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors. Trial registration Clinicaltrials.gov NCT02181101 . Registered September 2005.

Background Circulating tumour cells (CTCs) have been found to be a prognostic marker for reduced disease free survival, breast cancer–specific survival, and overall survival before the start of systemic treatment. Methods A total of 200 patients’ sera were included in this study, 100 patients being CTC positive and 100 patients being CTC negative. Matching criteria were histo-pathological grading, lymph node metastasis, hormone receptor status, TNM classification and survived breast cancer patients vs. deceased tumor associated patients. A multi cytokine/chemokine array was used to screen the sera for the angiogenic markers. Results Statistical significant correlation was exposed for sFlt1 values in regard to the CTC-Status. CTC negative patients displayed increased sFlt1 expression opposed to CTC positive breast cancer patients. Furthermore, significant enhanced PIGF values were also disclosed in CTC negative patients compared to patients being CTC positive. Analyzing the living patient collective we found significant differences in sFlt1 and PlGF values in regard to CTC negative and CTC positive patients. Conclusion Both vascular markers showed enhanced expression in the CTC negative patient collective. To continue, the collective graded G2 showed significantly enhanced sFlt1 expressions amongst patients with no CTCs. Moreover, the patient collective with no lymph node metastasis and CTC negativity indicated statistically significant increased sFlt1 values. A functional interaction of sFlt1 and PlGF was found, suggesting that their overexpression in tumour cells inhibits CTCs entering the peripheral blood. Furthermore, in regard to CTC negativity, sFlt1 and PlGF values may potentially serve as predictive markers. Trial registration The TRN of this study is NCT02181101 and the date of registration was the 4 th of June 2014. The study was retrospectively registered.

Background Galectin-1 (gal-1) belongs to the family of β-galactoside-binding proteins which primarily recognizes the Galβ1-4GlcNAc sequences of oligosaccharides associated with several cell surface glycoconjugates. The lectin recognizes correspondent glycoepitopes on human breast cancer cells. Galectin-1 is expressed both in normal and malignant tissues. Lymphatic organs naturally possessing high rates of apoptotic cells, express high levels of Galectin-1. Furthermore galectin-1 can initiate T cell apoptosis. Binding of galectin-1 to trophoblast tumor cells presenting the oncofetal Thomsen-Friedenreich (TF) carbohydrate antigen inhibits tumor cell proliferation. In this study we examined the impact galectin-1 has in vitro on cell proliferation, apoptotic potential and metabolic activity of MCF-7 and T-47D breast cancer cells in dependence to their expression of the Thomsen-Friedenreich (TF) tumor antigen. Methods For proliferation and apoptosis assays cells were grown in presence of 10, 30 and 60 μg gal-1/ml medium. Cell proliferation was determined by a BrdU uptake ELISA. Detection of apoptotic cells was done by M30 cyto death staining, in situ nick translation and by a nucleosome ELISA method. Furthermore we studied the impact galectin-1 has on the metabolic activity of MCF-7 and T-47D cells in a homotypic three-dimensional spheroid cell culture model mimicking a micro tumour environment. Results Gal-1 inhibited proliferation of MCF-7 cells (strong expression of the TF epitope) but did not significantly change proliferation of T-47D cells (weak expression of the TF epitope). The incubation of MCF-7 cells with gal-1 raised number of apoptotic cells significantly. Treating the spheroids with 30 μg/ml galectin-1 in addition to standard chemotherapeutic regimes (FEC, TAC) resulted in further suppression of the metabolic activity in MCF-7 cells whereas T-47D cells were not affected. Conclusions Our results demonstrate that galectin-1 can inhibit proliferation und metabolic cell activity and induce apoptosis in breast tumor cell lines with high expression levels of the Thomsen-Friedenreich (TF) antigen in monolayer and spheroid cell culture models.