Konrad Wilhelm

// Antje Neeb 1,* , Simon Hefele 2,* , Stefanie Bormann 1,8 , Walther Parson 3,4 , Fabian Adams 5 , Philipp Wolf 5 , Arkadiusz Miernik 5 , Martin Schoenthaler 5 , Malte Kroenig 5 , Konrad Wilhelm 5 , Wolfgang Schultze-Seemann 5 , Sigrun Nestel 6 , Georg Schaefer 7 , Huajie Bu 7 , Helmut Klocker 7 , Irina Nazarenko 2,* and Andrew C. B. Cato 1,* 1 Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Eggenstein-Leopoldshafen, Germany 2 Department of Environmental Health Sciences and Hospital Infection Control, Medical Center-University of Freiburg, Freiburg, Germany 3 Institute of Legal Medicine, Innsbruck Medical University, Innsbruck, Austria 4 Penn State Eberly College of Science, University Park, PA, USA 5 Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany 6 Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany 7 Department of Urology, Division of Experimental Urology, Innsbruck Medical University, Innsbruck, Austria 8 Heinrich Heine University, Institute of Toxicology, Düsseldorf, Germany * These authors contributed equally to this work Correspondence: Antje Neeb, email: // Irina Nazarenko, email: // Keywords : Anterior gradient 2 gene, Exosomes, Prostate cancer diagnosis, Urinary biomarkers, Splice variants Received : June 16, 2014 Accepted : August 18, 2014 Published : August 19, 2014 Abstract Anterior gradient 2 (AGR2) is a gene predominantly expressed in mucus-secreting tissues or in endocrine cells. Its expression is drastically increased in tumors including prostate cancer. Here we investigated whether AGR2 transcript levels can be used as a biomarker to detect prostate cancer (PCa). Using a PCR-based approach, we could show that in addition to the wild-type (AGRwt long and short) transcripts, five other AGR2 splice variants (SV) (referred to as AGR2 SV-C, -E, -F, -G and -H) were present in cancer cell lines. In tissue biopsies, SV-H and AGR2wt (short) distinguished between benign and PCa (p ≤ 0.05 n = 32). In urine exosomes, AGR2 SV-G and SV-H outperformed serum PSA. Receiver operating characteristic (ROC) curves showed the highest discriminatory power of SV-G and SV-H in predicting PCa. AGR2 SV-G and SV-H are potential diagnostic biomarkers for the non-invasive detection of PCa using urine exosomes.

BACKGROUND AND PURPOSE: Objective parameters for the classification of ureteral injuries and resulting indications for ureteral stent placement after ureteroscopy are lacking. We hereby present a new classification system including proof of interrater reliability and validation of recommendations for postoperative ureteral stent placement. PATIENTS AND METHODS: The Postureteroscopic Lesion Scale (PULS) was applied in 435 patients undergoing ureteroscopy. Interrater reliability between three surgeons (junior resident, senior resident, and specialist) was evaluated in 112 patients. Postoperative ureteral stent placement was performed according to PULS. For follow-up with ultrasonography, we assumed hydronephrosis to be an indirect sign for significant postoperative ureteral obstruction. RESULTS: No ureteral lesion was seen in 46.2% of patients (grade 0). A grade 1, 2, or 3 lesion was seen in 30.8%, 19.1%, and 3.9% of patients, respectively. No grade 4 or 5 lesions were observed in our series. Interrater reliability was high (Kendall W=0.91; mean Spearman Rho=0.86). This was particularly true between senior resident and specialist (Rho=0.95), compared with junior resident and senior resident or specialist (Rho=0.83, Rho=0.79, respectively). All patients with documented lesions had a Double-J stent placed. Indwelling time varied according to PULS. Results of a postoperative ultrasonographic follow-up could be obtained in 95.6% of cases. No patient showed clinical or sonographic signs of upper urinary tract obstruction. CONCLUSIONS: According to these preliminary data for the clinical application of PULS, interrater reliability is high. Standardized empiric recommendations for the use and duration of postoperative stent placement after ureteroscopy might be useful in guiding urologists in this conversely discussed issue, ultimately preventing ureteral strictures as a late complication of ureteroscopy. These will have to be confirmed, however, by controlled trials in the future.