No abstract

Endothelin-1 (ET-1) and its receptors (ET A R and ET B R), referred to as the endothelin (ET) axis, are overexpressed in breast carcinomas and appear to influence tumour growth and progression. The objective of this study was to determine the effect of expression of the ET axis in breast carcinomas on response to cytotoxic chemotherapy. The study included 44 patients with locally advanced breast cancer participating in a prospective phase III study evaluating high-dose neoadjuvant chemotherapy of epirubicin and cyclophosphamide. Expression of ET-1, ET A R and ET B R was determined by semiquantitative immunohistochemical analysis of breast cancer tissue from prechemotherapy tru-cut biopsies. Immunohistochemical staining was positive for ET-1 in 61.5%, for ET A R in 35% and for ET B R in 35.9% of breast carcinomas. Pathological response to chemotherapy was significantly decreased in ET A Rpositive patients (P ¼ 0.002). In total, 50% of ET A R-positive patients as compared to 7.7% of ET A R-negative patients attained pathologically 'no change'. Logistic regression confirmed ET A R as an independent predictive marker for pathological response (P ¼ 0.009). These data indicate that increased expression of ET A R in breast carcinomas is associated with resistance to chemotherapy. Determination of ET A R status may serve as a predictive marker for identifying patients less likely to be responsive to conventional chemotherapy.

We report about the 2-year results of a physician-based active cost management model for oncological therapies in a German OB/GYN university clinic. Over 2 years more than 4,000 oncological cycles were prospectively and individually analyzed regarding costs and reimbursement mode. Main aim was reducing costs without lowering cycle number and standard of care. Within two years pharmaceutical costs were reduced by 83.4% or 785,976.- EUR. All causes for a previous financial loss were identified and eliminated. Debts were paid back and employment of new staff and investments were possible. With this first active cost management model by and for physicians, oncological therapies can be performed cost covering even in a university clinic. Although developed for optimization of cost coverage of oncological therapies in Germany, this model is universally transferable.

Wax has been used for illustration purposes back to antiquity. Since the renaissance period human anatomy and different diseases have often been depicted in wax. During the last century the art of moulage preparation evolved to three-dimensional, realistic representations of diseased parts of the human body. Its heyday and wide spread distribution paralleled the growing independence of dermatology. Apart from few exceptions, most mouleurs did not permit access to their technique either to successors or the public. Just like other European hospitals, the Department of Dermatology at Kiel University houses a comprehensive collection of moulages dating back to a century. The 455 objects left today were collected by Professor Viktor Felix Karl Klingmüller (1870-1942) who was head of the department from 1906 to 1937. The mouleur Alfons Kröner from Breslau who died 1937 supplied most (354) of the wax models. Highly esteemed at his time, Kröner was quite secretive about his art of moulagig. 35 of his moulages bear the abbreviation "DRP" standing for Deutsches Reichspatent (German patent); Kröner was granted a patent in 1902. In his patent application both wax mixtures and technical procedure of moulaging are described in great detail. Kröner, similarly to Jules Baretta (Paris), coloured his moulages at the back of the wax layers. Applying for a patent demonstrates his effort to meet increasing commercial pressure among suppliers of teaching aids at that time. Knowledge of individual technical procedures is essential for medical history as well as proper restauration of moulages as they continually deteriorate with time. Because of their three-dimensional and realistic disease representations, moulages still compare well to modern media used today. Consequently, the "dying of moulages" concerning the wax objects themselves as well as public or medical interest has to be stopped to preserve moulages for future generations.

Even in elderly patients, greater consideration is now being given to tumor volume reduction in locally advanced breast cancer, with increased subsequent breast-conserving surgery. Neoadjuvant endocrine therapy offers the possibility of testing therapeutic efficacy in vivo, which is of great importance for optimal adjuvant treatment. Resulting therapy modifications can be expected to increase disease-free as well as overall survival. Recent results indicate that remission rates with primary chemotherapy are significantly lower in receptor-positive than in receptor-negative breast cancer and that efficacy parameters in receptor-positive tumors tend to favor primary endocrine therapy, highlighting the increased importance of this type of treatment. Aromatase inhibitors are superior to tamoxifen in terms of clinical response as well as breast conservation rate. Results from a small number of studies suggest that prolonged preoperative aromatase inhibitor therapy for up to 12 months can increase the rate of clinical and pathological complete remissions. In conclusion, primary endocrine therapy is a valid therapeutic option for postmenopausal patients with locally advanced hormone receptor-positive breast cancer and significant comorbidity, increased risk of complications with regard to anesthesia and surgery, desire for breast-conserving surgery and/or reduced suitability for chemotherapy, as well as in very old patients.