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Krefeld, Germany

Rink M.,University of Hamburg | Rink M.,Cornell University | Chun F.K.,University of Hamburg | Dahlem R.,University of Hamburg | And 12 more authors.
European Urology | Year: 2012

Background: Preliminary research has suggested the potential prognostic value of circulating tumor cells (CTC) in patients with advanced nonmetastatic urothelial carcinoma of the bladder (UCB). Objective: Prospectively analyze the clinical relevance and human epidermal growth factor receptor 2 (HER2) expression of CTC in patients with clinically nonmetastatic UCB. Design, setting, and participants: Blood samples from 100 consecutive UCB patients treated with radical cystectomy (RC) were investigated for the presence (CellSearch system) of CTC and their HER2 expression status (immunohistochemistry). HER2 expression of the corresponding primary tumors and lymph node metastasis were analyzed using fluorescence in situ hybridization. Intervention: Blood samples were taken preoperatively. Patients underwent RC with lymphadenectomy. Measurements: Outcomes were assessed according to CTC status. HER2 expression of CTC was compared with that of the corresponding primary tumor and lymph node metastasis. Results and limitations: CTC were detected in 23 of 100 patients (23%) with nonmetastatic UCB (median: 1; range: 1-100). Presence, number, and HER2 status of CTC were not associated with clinicopathologic features. CTC-positive patients had significantly higher risks of disease recurrence and cancer-specific and overall mortality (p values: ≤0.001). After adjusting for effects of standard clinicopathologic features, CTC positivity remained an independent predictor for all end points (hazard ratios: 4.6, 5.2, and 3.5, respectively; p values ≤0.003). HER2 was strongly positive in CTC from 3 of 22 patients (14%). There was discordance between HER2 expression on CTC and HER2 gene amplification status of the primary tumors in 23% of cases but concordance between CTC, primary tumors, and lymph node metastases in all CTC-positive cases (100%). The study was limited by its sample size. Conclusions: Preoperative CTC are already detectable in almost a quarter of patients with clinically nonmetastatic UCB treated with RC and were a powerful predictor of early disease recurrence and cancer-specific and overall mortality. Thus CTC may serve as an indication for multimodal therapy. Molecular characterization of CTC may serve as a liquid biopsy to guide individual targeted therapy in future clinical trials. © 2012 European Association of Urology. Source


Wojcinski S.,Hannover Medical School | Stefanidou N.,Helios Hospital Krefeld | Hillemanns P.,Hannover Medical School | Degenhardt F.,Franziskus Hospital Bielefeld
BMC Women's Health | Year: 2013

Background: The aim of this study was to evaluate the relation of some ultrasound morphological parameters to biological characteristics in breast carcinoma.Methods: Ultrasound data from 315 breast masses were collected. We analyzed the ultrasound features of the tumors according to the ACR BI-RADS®-US classification system stratified by hormone receptor status, HER2 status, histology grade, tumor type (ductal versus lobular), triple-negativity, breast density, tumor size, lymph node involvement and patient's age.Results: We found a variety of ultrasound features that varied between the groups. Invasive lobular tumors were more likely to have an angulated margin (39% versus 22%, p = 0.040) and less likely to show posterior acoustic enhancement (3% versus 16%, p = 0.023) compared to invasive ductal carcinoma. G3 tumors were linked to a higher chance of posterior acoustic enhancement and less shadowing and the margin of G3 tumors was more often described as lobulated or microlobulated compared to G1/G2 tumors (67% versus 46%, p = 0.001). Tumors with an over-expression of HER2 exhibited a higher rate of architectural distortions in the surrounding tissue, but there were no differences regarding the other features. Hormone receptor negative tumors were more likely to exhibit a lobulated or microlobulated margin (67% versus 50%, p = 0.037) and less likely to have an echogenic halo (39% versus 64%, p = 0.001). Furthermore, the posterior acoustic feature was more often described as enhancement (33% versus 13%, p = 0.001) and less often as shadowing (20% versus 47%, p < 0.001) compared to hormone receptor positive tumors.Conclusion: Depending on their biological and clinical profile, breast cancers are more or less likely to exhibit the typical criteria for malignancy in ultrasound. Moreover, certain types of breast cancer tend to possess criteria that are usually associated with benign masses. False-negative diagnosis may result in serious consequences for the patient. For the sonographer it is essential to be well aware of potential variations in the ultrasound morphology of breast tumors, as described in this paper. © 2013 Wojcinski et al.; licensee BioMed Central Ltd. Source


Lainka E.,University of Duisburg - Essen | Bielak M.,University of Duisburg - Essen | Lohse P.,Ludwig Maximilians University of Munich | Lohse P.,Institute for Laboratory Medicine and Human Genetics | And 5 more authors.
European Journal of Pediatrics | Year: 2012

Familial Mediterranean fever (FMF) is an autoinflammatory disease and belongs to the heterogeneous group of hereditary recurrent fever syndromes (HRFs). Aims: The aims of the study were to determine the incidence of FMF in Germany and to describe the spectrum of pyrin mutations and the clinical characteristics in children. A prospective surveillance of children with HRF including FMF was conducted in Germany during a time period of 3 years by the German paediatric surveillance unit for rare paediatric diseases (ESPED). Monthly inquiries were sent to 370 children's hospitals (Clinic-ESPED, n1) and to 23 laboratories (Laboratory-ESPED, n2). Inclusion criteria were children ≤16 years of age, disease-associated pyrin mutations, and more than three self-limiting episodes of fever >38.5 C with increased inflammation markers. In n1, 122 patients with FMF and 225 pyrin mutations were identified. Ninety-two of 122 (75 %) children were of Turkish origin. The minimum incidence of FMF was estimated to be 3 (95 % CI: 2.48-3.54) per 106 person-years in the whole children population and 55 (95 % CI: 46-66) per 106 person-years in Turkish children living in Germany. N1 U n2 amounted to 593 asymptomatic and symptomatic carriers of 895 mutations (overlap of 73 cases with 134 mutations). p.Met694Val (45 %), p.Met680Ile (14 %), p.Val726Ala (12 %), and p.Glu148Gln (11.5 %) were the most common pyrin mutations. Conclusions: Despite FMF being the most frequent of the HRFs, its incidence in Germany is low. Twenty-five to 50 FMF patients ≤16 years are newly diagnosed per year. The disease is most commonly observed in individuals of Turkish ancestry. Key Messages • The incidence of FMF in Germany is calculated as 3 per 10 6 person-years for the entire children population and as 55 per 10 6 person-years for children of Turkish ancestry. • The pyrin p.Met694Val, p.Met680Ile, p.Val726Ala, and p.Glu148Gln mutations are the prevailing missense mutations. • The awareness of the disease symptoms, especially for children with a migration background, must be increased, and the management of FMF as the most common AID must be improved. © 2012 Springer-Verlag. Source


Thill M.,University of Lubeck | Terjung A.,Helios Hospital Krefeld | Friedrich M.,Helios Hospital Krefeld
European Journal of Gynaecological Oncology | Year: 2014

Up until now there have been many advances in treatment options for breast cancers such as targeted therapies like monoclonal antibodies, tyrosine kinase inhibitors, mTOR antagonists, and vaccines. Despite these advances, there are still many more that warrant further exploration. Two of these targets might be the cyclooxygenase-2 (COX-2), the key enzyme required to convert arachidonic acid to prostaglandins, and calcitriol [1,25(OH)2D3] which is the biologically active form of vitamin D. Both calcitriol and the inhibition of COX-2 have shown antiproliferative and prodifferentiation, as well as pro-apoptotic effects in different malignancies in vitro and in vivo, and the key prostaglandin catabolic enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is known to have tumor suppressor activity. Furthermore, the combination of calcitriol and nonsteroidal anti-inflammatory drugs (NSAIDs), such as non-selective and selective COX-2 inhibitors, acting synergistically to achieve significant cell growth inhibition in prostate cancer. Some epidemiological studies suggest that vitamin D confers a moderate benefit against breast cancer while most epidemiological studies presume that NSAIDs confer the same. Nevertheless there is growing body of evidence that COX-2 expression is a fundamental step in breast cancer carcinogenesis. To date, clinical trials have been conducted in patients with different malignancies using treatment strategies including COX-2 inhibitors and calcitriol and are showing partially encouraging results. The goal of this review is to shed light on the association between the prostaglandin as well as vitamin D metabolism relating to the incidence and therapy of breast cancers. Moreover, this review will also highlight potential treatment options, as well as extract any existing interactions between the two metabolisms. Source


Tolsdorff B.,University of Wurzburg | Pommert A.,MAN Group | Hohne K.H.,MAN Group | Petersik A.,MAN Group | And 3 more authors.
Laryngoscope | Year: 2010

Objectives/Hypothesis: Virtual surgical training systems are of growing value. Current prototypes for endonasal sinus surgery simulation are very expensive or lack running stability. No reliable system is available to a notable number of users yet. The purpose of this work was to develop a dependable simulator running on standard PC hardware including a detailed anatomic model, realistic tools and handling, stereoscopic view, and force feedback. Study Design: Descriptive. Methods: A three-dimensional voxel model was created based on a high-resolution computed tomography study of a human skull, from which the bony structures were segmented. The mucosa and organs at risk were added manually. The model may be manipulated with virtual surgical tools controlled with a low-cost haptic device, which is also used to adjust microscopic or endoscopic views. Visualization, haptic rendering, and tissue removal are represented with subvoxel resolution. Results: The handling of the model is convincing. The haptic device provides a realistic feeling regarding the interaction between tool tip and anatomy. Three-dimensional orientation and the look and feel of virtual surgical interventions get close to reality. Conclusions: The newly developed system is a stable, fully operational simulator for sinus surgery based on standard PC hardware. Besides the limitations of a low-cost haptic device, the presented system is highly realistic regarding anatomy, visualization, manipulation, and the appearance of the tools. It is mainly intended for gaining surgical anatomy knowledge and for training navigation in a complex anatomical environment. Learning effects, including motor skills, have yet to be quantified. © 2009 The American Laryngological, Rhinological and Otological Society, Inc. Source

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