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Wiesbaden, Germany

Noske A.,University of Zurich | Noske A.,Charite - Medical University of Berlin | Loibl S.,German Breast Group | Darb-Esfahani S.,Charite - Medical University of Berlin | And 14 more authors.
Breast Cancer Research and Treatment | Year: 2011

Human epidermal growth factor receptor 2 (HER2) testing is an essential part of pathological assessment in breast cancer patients, as HER2 provides not only prognostic but also predictive information on response to targeted therapy. So far, HER2 test accuracy of immunohistochemistry/in situ-hybridization techniques is still under debate, and more reliable and robust technologies are needed. To address this issue and to evaluate the predictive value of HER2 on chemotherapy, we investigated a cohort of 278 patients from the GeparTrio trial, a prospective neoadjuvant anthracycline/taxane-based multicenter study. In the GeparTrio trial, patients were not treated with any anti-HER2 therapy, as this was not standard therapy at this time. The HER2 status was analyzed by three different approaches: local and central evaluation using immunohistochemistry combined with in situ-hybridization as well as evaluation of HER2 mRNA expression using kinetic RT-PCR from formalin-fixed, paraffin-embedded (FFPE) tissue samples using a predefined cutoff. HER2 overexpression/amplification was observed in 37.3% (91/244) and 17.9% (41/229) of the informative samples in the local and central evaluations, respectively. Positive HER2 mRNA levels were found in 19.8% (55/278). We observed a highly significant correlation between central HER2 expression and HER2 status measured by kinetic RT-PCR (r = 0.856, P < 0.0001) and an overall agreement of 95.6% (κ statistic, 0.862, CI 0.77-0.94). Further, central HER2 as well as HER2 mRNA expression were predictors for a pathological complete response after neoadjuvant anthracycline/taxane-based primary chemotherapy in a univariate binary logistic regression analysis (OR 3.29, P = 0.002; OR 2.65, P = 0.004). The predictive value could be confirmed for the central HER2 status by multivariate analysis (OR 3.04, P = 0.027). The locally assessed HER2 status was not predictive of response to chemotherapy. Our results suggest that standardized methods are preferable for evaluation of HER2 status. The kinetic RT-PCR from FFPE tissue might be an additional approach for assessment of this important prognostic and predictive parameter but has to be confirmed by other studies. © 2010 Springer Science+Business Media, LLC.

Sinn B.V.,Charite - Medical University of Berlin | Von Minckwitz G.,German Breast Group | Denkert C.,Charite - Medical University of Berlin | Eidtmann H.,Universitatsklinikum Schleswig Holstein | And 12 more authors.
Annals of Oncology | Year: 2013

Background: Mucin-1 (MUC1) is a promising antigen for the development of tumor vaccines. We evaluated the frequency of MUC1 expression and its impact on therapy response and survival after neoadjuvant chemotherapy for breast cancer. Patients and methods: Pre-treatment core biopsies of patients from the GeparTrio neoadjuvant trial (NCT 00544765) were evaluated for MUC1 by immunohistochemistry (IHC; N = 691) and quantitative RT-PCR (qRT-PCR; N = 286) from formalin-fixed paraffin-embedded (FFPE) samples. Results: MUC1 protein and mRNAwas detectable in the majority of cases and was associated with hormone-receptorpositive status (P < 0.001). High MUC1 protein and mRNA expression were associated with lower probability of pathologic complete response (P = 0.017 and P < 0.001) and with longer patient survival (P = 0.03 and P < 0.001). In multivariable analysis, MUC1 protein and mRNA expression were independently predictive (P = 0.001 and P < 0.001). MUC1 protein and mRNA expression were independently prognostic for overall survival (P = 0.029 and P = 0.015). Conclusions: MUC1 is frequently expressed in breast cancer and detectable on mRNA and protein level from FFPE tissue. It provides independent predictive information for therapy response and survival after neoadjuvant chemotherapy. In clinical immunotherapy trials, MUC1 expression may serve as a predictive marker. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Elsen C.,St. Josefs Hospital Wiesbaden | Rivas-Echeverria C.,Programa de Prevencion de Preeclampsia PPP | Sahland K.,Programa de Prevencion de Preeclampsia PPP | Sanchez R.,Programa de Prevencion de Preeclampsia PPP | And 6 more authors.
Geburtshilfe und Frauenheilkunde | Year: 2012

In the course of the prospective, randomized, double-blind trial the influence of a high-dose riboflavin substitution on the risk for preeclampsia was studied in a high-risk collective 1. The present contribution evaluates supplementary data from the already published PROPER trial. The patients were from the two study centers Mérida, Venezuela, and Moshi, Tanzania, they were randomized from the 20th week of pregnancy and received either 15mg riboflavin daily or placebo. Clinical and laboratory checks were carried out at four-week intervals up to childbirth. Concerning the question of whether there is a relationship between the serum levels of antioxidative vitamins and the risk of developing preeclampsia, it was found that no relationship could be detected between the measured laboratory values of vitamins E, A and Band the total risk of developing a hypertensive disease of pregnancy. On comparisons between patients with severe preeclampsia, those with a mild form, and the general healthy population, however, significant differences in the levels of antioxidative vitamins E and A as well as the FAD level were seen. The patients from Tanzania showed on the whole significantly lower vitamin levels than those from Venezuela, possibly due to the better nutritional situation in Venezuela. Considering the results altogether, the role of antioxidative parameters in the pathophysiology of preeclampsia remains unclear. However, the collected data provide valuable hints for future preventative strategies. © Georg Thieme Verlag KG Stuttgart, New York.

Kutzner K.P.,St. Josefs Hospital Wiesbaden | Kovacevic M.P.,St. Josefs Hospital Wiesbaden | Roeder C.,University of Bern | Rehbein P.,St. Josefs Hospital Wiesbaden | Pfeil J.,St. Josefs Hospital Wiesbaden
International Orthopaedics | Year: 2015

Purpose: Despite the fact that new and modern short-stems allow bone sparing and saving of soft-tissue and muscles, we still face the challenge of anatomically reconstructing the femoro-acetabular offset and leg length. Therefore a radiological and clinical analysis of a short-stem reconstruction of the femoro-acetabular offset and leg length was performed. Methods: Using an antero-lateral approach, the optimys short-stem (Mathys Ltd, Bettlach, Switzerland) was implanted in 114 consecutive patients in combination with a cementless cup (Fitmore, Zimmer, Indiana, USA; vitamys RM Pressfit, Mathys Ltd, Bettlach, Switzerland). Pre- and postoperative X-rays were done in a standardized technique. In order to better analyse and compare X-ray data a special double coordinate system was developed for measuring femoral- and acetabular offset. Harris hip score was assessed before and six weeks after surgery. Visual analogue scale (VAS) satisfaction, leg length difference and the existence of gluteal muscle insufficiency were also examined. Results: Postoperative femoral offset was significantly increased by a mean of 5.8 mm. At the same time cup implantation significantly decreased the acetabular offset by a mean of 3.7 mm, which resulted in an increased combined femoro-acetabular offset of 2.1 mm. Postoperatively, 81.7 % of patients presented with equal leg length. The maximum discrepancy was 10 mm. Clinically, there were no signs of gluteal insufficiency. No luxation occurred during hospitalization. The Harris hip score improved from 47.3 before to 90.1 points already at six weeks after surgery while the mean VAS satisfaction was 9.1. Conclusion: The analysis showed that loss of femoro-acetabular offset can be reduced with an appropriate stem design. Consequently, a good reconstruction of anatomy and leg length can be achieved. In the early postoperative stage the clinical results are excellent. © 2014, The Author(s).

Kutzner K.P.,St. Josefs Hospital Wiesbaden | Freitag T.,University of Ulm | Kovacevis M.-P.,St. Josefs Hospital Wiesbaden | Pfeil D.,St. Josefs Hospital Wiesbaden | And 2 more authors.
International Orthopaedics | Year: 2016

Purpose: The hypothesis of this study was that femoral implant migration would not differ between simultaneous bilateral or unilateral short-stem THA. Method: Implant migration of 202 femoral short-stems (100 unilateral and 102 one-stage bilateral cases) in 151 patients was assessed by “Ein-Bild-Roentgen-Analysis Femoral-Component-Analysis” in a two years follow-up (2.0-3.0 years). Migration patterns of unilateral and simultaneous cases were analysed and compared. Results: There was no difference between the two groups regarding age, body mass index and gender. After two years mean subsidence of all 202 implants was 1.43 mm (-6.5 mm to 2.0 mm). After initial subsidence of 0.37 mm per month within the first six weeks, the mean monthly migration was reduced to 0.02 mm between one and two years post-operative. There was no statistical difference in mean migration between unilateral (1.34 mm) and simultaneous bilateral (1.51 mm) THA (p = 0.33). Conclusion: In summary, two years post-operative there was no difference in the amount of mean implant subsidence between unilateral compared to simultaneous bilateral short-stem THA. This suggests that regarding implant fixation simultaneous bilateral short-stem THA is as safe and successful as a solely unilateral intervention. © 2016 SICOT aisbl

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