Empirische Befunde zur Entwicklung der Lebensverhältnisse in den Ländern Sachsen, Sachsen-Anhalt und Thüringen

Ein wesentliches Leitziel der Raumordnungspolitik in Deutschland ist es, gleichwertige Lebensverhältnisse in allen Teilräumen herzustellen. Die Frage, was heute unter diesem in § 1 Abs. 2 ROG formuliertem Leitziel zu verstehen ist, wird unter Fachleuten und im politischen Raum intensiv diskutiert. Das Sozialstaatsprinzip (Art. 20 Abs. 1 GG) und Artikel 72 Abs. 2 GG gelten allgemein als politische Forderung, zurückgebliebene Regionen so zu entwickeln, dass sie einen Anschluss an die Gebiete finden können, die die Spitze der wirtschaftlichen und gesellschaftlichen Entwicklung darstellen. Dies zeigt die wachstumsorientierte Politik in den 70er und 80er Jahren in Westdeutschland, die darauf ausgerichtet war, durch gezielte Förderprogramme zum Abbau regionaler Disparitäten beizutragen. Ein Süd-Nord-Gefälle blieb jedoch, wie der Raumordnungsbericht des Bundes von 1986 zeigt, innerhalb der damaligen Bundesrepublik bestehen. Wesentlich größere Disparitäten zeigten sich allerdings mit der Einheit Deutschlands im West-Ost-Gefälle. Anhand von ausgewählten, für die Bewertung der Lebensverhältnisse relevanten Indikatoren sollen in diesem Beitrag der Zustand und die Entwicklung der drei mitteldeutschen Bundesländer dargestellt werden.One of the key goals of spatial-planning policy in Germany is the creation of balanced living conditions throughout all sections of the national territory. Just how this requirement – contained in Section 1 para. 2 of the Federal Regional Planning Act (ROG) – is to be interpreted today is a matter of intensive debate both among planning experts and in political circles. The “social state principle” (Article 20 para. 1 of the Basic Law) together with Article 72 para. 2 are generally regarded as the political mandate to promote development in laggard regions to such an extent that they remain within reach of those areas which represent the spearheads of economic and social development. This is reflected in the growth-oriented policies of the 1970s and ’80s in West Germany, which employed targeted economic-assistance programmes specifically as a means of mitigating regional disparities. Nonetheless, within the then Federal Republic of Germany there remained a north-south divide, as attested by the Federal Government’s spatial planning report in 1986. German unification, however, revealed significantly greater disparities between east and west. Drawing on three selected indicators relevant to assessing living conditions, this paper describes conditions and developments in three states of central Germany

Benign Breast Tumours - Diagnosis and Management

With improvements in breast imaging, mammography, ultrasound and minimally invasive interventions, the detection of early breast cancer, non-invasive cancers, lesions of uncertain malignant potential, and benign lesions has increased. However, with the improved diagnostic capabilities comes a substantial risk of false-positive benign lesions and vice versa false-negative malignant lesions. A statement is provided on the manifestation, imaging, and diagnostic verification of isolated benign breast tumours that have a frequent manifestation, in addition to general therapy management recommendations. Histological evaluation of benign breast tumours is the most reliable diagnostic method. According to the S3 guideline and information gained from analysis of the literature, preference is to be given to core biopsy for each type of tumour as the preferred diagnostic method. An indication for open biopsy is also to be established should the tumour increase in size in the follow-up interval, after recurring discrepancies in the vacuum biopsy results, or at the request of the patient. As an alternative, minimally invasive procedures such as therapeutic vacuum biopsy, cryoablation or high-intensity focused ultrasound are also becoming possible alternatives in definitive surgical management. The newer minimally invasive methods show an adequate degree of accuracy and hardly any restrictions in terms of post-interventional cosmetics so that current requirements of extensive breast imaging can be thoroughly met

Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: A phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy

<p>Abstract</p> <p>Background</p> <p>In recent years, preoperative volume reduction of locally advanced breast cancers, resulting in higher rates of breast-conserving surgery (BCS), has become increasingly important also in postmenopausal women. Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors (AIs), including letrozole, for such neoadjuvant endocrine treatment. This usually lasts 3–4 months and has been extended to up to 12 months, but optimal treatment duration has not been fully established.</p> <p>Methods</p> <p>This study was designed as a multicenter, open-label, single-arm, exploratory phase IIb/III clinical trial of letrozole 2.5 mg, one tablet daily, for 4–8 months. The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration. Tumor regression (by clinical examination, mammography, and ultrasound), shift towards BCS eligibility, and safety assessments were the main outcome measures. Standard parametric and nonparametric descriptive statistics were performed.</p> <p>Results</p> <p>Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women (median (range): 67.0 (56–85) years) with unilateral, initially BCS-ineligible primary breast cancer (clinical stage ≥ T2, N0, M0). Letrozole treatment duration in the modified intent-to-treat (ITT; required 4 months' letrozole treatment) analysis population (29 patients) was 4 months in 14 patients and > 4 months in 15 patients. The respective per-protocol (PP) subgroup sizes were 14 and 11. The majority of partial or complete responses were observed at 4 months, though some beneficial responses occurred during prolonged letrozole treatment. Compared with baseline, median tumor size in the ITT population was reduced by 62.5% at Month 4 and by 70.0% at final study visit (Individual End). Similarly, in the PP population, respective reductions were 64.0% and 67.0%. Whereas initially all patients were mastectomy candidates, letrozole treatment enabled BCS (lumpectomy) in 22 ITT (75.9%) and 18 PP (72.0%) patients.</p> <p>Conclusion</p> <p>Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment. While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients, there is no clear optimum for treatment duration. Letrozole has a favorable overall safety and tolerability profile.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier NCT00535418.</p

Synthese und Funktionalisierung von 2,3-Diacetamido-2,3-didesoxy-uronsäure-Derivaten

Diese Dissertation befasst sich mit der Synthese von D-gluco-, D-galacto- und D-manno-konfigurierten 2,3-Diacetamido-2,3-didesoxy-hexopyranosiden. Dabei konnte durch Oxidation und Reduktion an 6-C der D-gluco-, D-galacto- und D-manno-konfigurierten 2,3-Diacetamido-2,3-didesoxy-hexopyranoside korrespondierende Uronsäuren sowie 6-Desoxy-Verbindungen dargestellt werden. Die Uronsäure-Derivate wurden erfolgreich in Glykosyldonatoren durch Einführung geeigneter Schutzgruppen bzw. Aktivierung des anomeren Zentrums umgesetzt. Erste Glycosylierungen haben Disaccharide in 44 - 57 % Ausbeute ergeben

Testing chemotherapy efficacy in HER2 negative breast cancer using patient-derived spheroids

Background Targeted anti-HER2 therapy has greatly improved the prognosis for many breast cancer patients. However, treatment for HER2 negative disease is currently still selected from a multitude of untargeted chemotherapeutic treatment options. A predictive test was developed using patient-derived spheroids to identify the most effective therapy for patients with HER2 negative breast cancer of all stages, for clinically relevant subgroups, as well as individual patients. Methods Tumor samples from 120 HER2 negative patients obtained through biopsy or surgical excision were tested in the breast cancer spheroid model using scaffold-free cell culture. Similarly, spheroids were also generated from established HER2 negative breast cancer cell lines T-47D, MCF7, HCC1143, and HCC1937 to compare treatment efficacy of heterogeneous cell populations from patient tumor tissue with homogeneous cell lines. Spheroids were treated in vitro with guideline-recommended compounds. Treatment mediated impact on cell survival was subsequently quantified using an ATP assay. Results Differences were observed in the metabolic activity of the untreated spheroids, whereby cell lines consistently achieved higher values compared to tissue spheroids (p < 0.001). A higher number of cells per spheroid correlated with a higher basal metabolic activity in tissue-derived spheroids (p < 0.01), while the opposite was observed for cell line spheroids (p < 0.01). Recurrent tumors showed a higher mean vitality (p < 0.01) compared to primary tumors. Except for taxanes, treatment efficacy for most tested compounds differed significantly between breast cancer tissue spheroids and breast cancer cell lines. Overall a high variability in treatment response in vitro was seen in the tissue spheroids regardless of the tested substances. A greater response to anthracycline/docetaxel was observed for hormone receptor negative samples (p < 0.01). A higher response to 5-FU (p < 0.01) and anthracycline (p < 0.05) was seen in high grade tumors. Smaller tumor size and negative lymph node status were both associated with a higher treatment efficacy to anthracycline treatment combined with 5-FU (cT1/2 vs cT3/4, p = 0.035, cN+ vs cN−, p < 0.05). Conclusions The tissue spheroid model reflects current guideline treatment recommendations for HER2 negative breast cancer, whereas tested cell lines did not. This model represents a unique diagnostic method to select the most effective therapy out of several equivalent treatment options

The Predictive Value of PITX2 DNA Methylation for High-Risk Breast Cancer Therapy: Current Guidelines, Medical Needs, and Challenges

High-risk breast cancer comprises distinct tumor entities such as triple-negative breast cancer (TNBC) which is characterized by lack of estrogen (ER) and progesterone (PR) and the HER2 receptor and breast malignancies which have spread to more than three lymph nodes. For such patients, current (inter)national guidelines recommend anthracycline-based chemotherapy as the standard of care, but not all patients do equally benefit from such a chemotherapy. To further improve therapy decision-making, predictive biomarkers are of high, so far unmet, medical need. In this respect, predictive biomarkers would permit patient selection for a particular kind of chemotherapy and, by this, guide physicians to optimize the treatment plan for each patient individually. Besides DNA mutations, DNA methylation as a patient selection marker has received increasing clinical attention. For instance, significant evidence has accumulated that methylation of the PITX2 (paired-like homeodomain transcription factor 2) gene might serve as a novel predictive and prognostic biomarker, for a variety of cancer diseases. This review highlights the current understanding of treatment modalities of high-risk breast cancer patients with a focus on recommended treatment options, with special attention on the future clinical application of PITX2 as a predictive biomarker to personalize breast cancer management

Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: Phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6 × FEC versus 3 × FEC/3 × Docetaxel

Contains fulltext : 98255.pdf (publisher's version ) (Open Access)BACKGROUND: Today, more than 70% of patients with primary node-negative breast cancer are cured by local therapy alone. Many patients receive overtreatment by adjuvant chemotherapy due to inadequate risk assessment. So far, few clinical trials have prospectively evaluated tumor biology based prognostic factors. Risk assessment by a biological algorithm including invasion factors urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) will assess up to 35-55% of node-negative patients as low-risk and thus avoid chemotherapy. In contrast, a clinical-pathological algorithm will only classify 20-40% of patients as low-risk. High-risk node-negative patients should receive chemotherapy. Anthracycline-based regimens are accepted as a standard, the additional benefit of taxanes remains an open question. METHODS/DESIGN: The international NNBC3 ("Node Negative Breast Cancer 3-Europe") trial compares biological risk assessment (UP) using invasion factors uPA/PAI-1 with a clinical-pathological algorithm (CP). In this trial, the type of risk assessment (CP or UP) was chosen upfront by each center for its patients. Fresh frozen tissue was obtained to determine uPA/PAI-1 using an enzyme-linked immunosorbent assay (ELISA). Patients assessed as high-risk were stratified by human epidermal growth factor receptor 2 (HER2) status and then randomised to receive anthracycline-containing chemotherapy 5-Fluorouracil (F)/Epirubicin (E)/Cyclophosphymide (C) or an anthracycline-taxane sequence (FE(100)C*6 versus FE(100)C*3 followed by Docetaxel(100)*3). DISCUSSION: In this trial, 4,149 node-negative patients with operable breast cancer from 153 centers in Germany and France were included since 2002. Measurement of uPA/PAI-1 by ELISA was performed with standardised central quality assurance for 2,497 patients (60%) from 56 "UP"-centers. The NNBC 3-Europe trial showed that inclusion of patients into a clinical phase III trial is feasible based on biological testing of fresh frozen tumor material. In addition, 2,661 patients were classified as high-risk and thus received chemotherapy. As adjuvant chemotherapy, 1,334 high-risk patients received FE(100)C-Docetaxel(100), and 1,327 received French FE(100)C. No unexpected toxicities were observed. Chemotherapy efficacy and comparison of UP with CP will be evaluated after longer follow-up. TRIAL REGISTRATION: clinical Trials.gov NCT01222052

Ductoscopic Detection of Intraductal Lesions in Cases of Pathologic Nipple Discharge in Comparison with Standard Diagnostics: The German Multicenter Study

SummaryBackground: According to the literature, ductoscopy is gaining increasing importance in the diagnosis of intraductal anomalies in cases of pathologic nipple discharge. In a multicenter study, the impact of this method was assessed in comparison with that of standard diagnostics. Patients and Methods: Between 09/2006 and 05/2009, a total of 214 patients from 7 German breast centers were included. All patients underwent elective ductoscopy and subsequent ductal excision because of pathologic nipple discharge. Ductoscopy was compared with the following standard diagnostics: breast sonography, mammography, magnetic resonance imaging (MRI), galactography, cytologic nipple swab, and ductal lavage cytology. The histological and imaging results were compared and contrasted to the results obtained from the nipple swab and cytologic assessment. Results: Sonography had the highest (82.9%) sensitivity, followed by MRI (82.5%), galactography (81.3%), ductoscopy (71.2%), lavage cytology (57.8%), mammography (57.1%), and nipple swab (22.8%). Nipple swabs had the highest (85.5%) specificity, followed by lavage cytology (85.2%), ductoscopy (49.4%), galactography (44.4%), mammography (33.3%), sonography (17.9%), and MRI (11.8%). Conclusion: Currently, ductoscopy provides a direct intraoperative visualization of intraductal lesions. Sensitivity and specificity are similar to those of standard diagnostics. The technique supports selective duct excision, in contrast to the unselective technique according to Urban. Therefore, ductoscopy extends the interventional/diagnostic armamentarium