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Background: Stratification of cancer patients to identify those with worse prognosis is increasingly important. Through in silico analyses, we recently developed a gene expression-based prognostic score (S3-score) for clear cell renal cell carcinoma (ccRCC), using the cell type-specific expression of 97 genes within the human nephron. Herein, we verified the score using whole-transcriptome data of independent cohorts and extend its application for patients with metastatic disease receiving tyrosine kinase inhibitor treatment. Finally, we sought to improve the signature for clinical application using qRT-PCR., Methods: A 97 gene-based S3-score (S3 97 ) was evaluated in a set of 52 primary non-metastatic and metastatic ccRCC patients as well as in 53 primary metastatic tumors of sunitinib-treated patients. Gene expression data of The Cancer Genome Atlas (n = 463) was used for platform transfer and development of a simplified qRT-PCR-based 15-gene S3-score (S3 15 ). This S3 15 -score was validated in 108 metastatic and non-metastatic ccRCC patients and ccRCC-derived metastases including in part several regions from one metastasis. Univariate and multivariate Cox regression stratified by T, N, M, and G were performed with cancer-specific and progression-free survival as primary endpoints., Results: The S3 97 -score was significantly associated with cancer-specific survival (CSS) in 52 ccRCC patients (HR 2.9, 95% Cl 1.0-8.0, P Log-rank  = 3.3 × 10 -2 ) as well as progression-free survival in sunitinib-treated patients (2.1, 1.1-4.2, P Log-rank  = 2.2 × 10 -2 ). The qRT-PCR based S3 15 -score performed similarly to the S3 97 -score, and was significantly associated with CSS in our extended cohort of 108 patients (5.0, 2.1-11.7, P Log-rank  = 5.1 × 10 -5 ) including metastatic (9.3, 1.8-50.0, P Log-rank  = 2.3 × 10 -3 ) and non-metastatic patients (4.4, 1.2-16.3, P Log-rank  = 1.6 × 10 -2 ), even in multivariate Cox regression, including clinicopathological parameters (7.3, 2.5-21.5, P Wald  = 3.3 × 10 -4 ). Matched primary tumors and metastases revealed similar S3 15 -scores, thus allowing prediction of outcome from metastatic tissue. The molecular-based qRT-PCR S3 15 -score significantly improved prediction of CSS by the established clinicopathological-based SSIGN score (P = 1.6 × 10 -3 )., Conclusion: The S3-score offers a new clinical avenue for ccRCC risk stratification in the non-metastatic, metastatic, and sunitinib-treated setting.

Background: Urinary marker tests for bladder cancer (BC) detection and surveillance represent a desirable approach to diagnosis and follow-up. The SCIMEDX uCyt+ assay detects antigens expressed by BC cells (mucin glycoprotein and carcinoembryonic antigen) using green and red fluorescence and is interpreted according to specific manufacturer's recommendations. In the present study, we evaluated divergent approaches of numeric and morphological analysis of uCyt+ to generate a rationale for alternative test interpretation strategies., Methods: A total of 444 patients with hematuria and without history of BC underwent uCyt+ analysis, cystoscopy and histological examination of tissue biopsies. Beside positive cells according to the manufacturer's definition (definitely positive cells, DPC), (i) cells showing borderline character (borderline cells, BLC), and (ii) cells with staining present below defined border (subliminal cells, SLC) were included into the analytical algorithm. Different cut-off levels for cell counts (>0, ≥3, ≥5) were evaluated separately with regard to their diagnostic accuracy. Moreover, the influence of clinical factors on test results were evaluated., Results: Adding BLC at a cut-off of ≥3 cells resulted in Area Under the Curve (AUC) of 0.70 for green and 0.77 for red fluorescence, respectively. Adding SLC led to reduced AUC (0.62 and 0.73, respectively). Male gender was significantly associated with false positive results in the "best AUC" groups (P = .0101). No further correlations to clinical influencing factors were observed., Conclusions: Adding microscopic BLC as test-positive and adjusting cut-off level for the interpretation of uCyt+ may improve assay performance independent of clinical factors., (© 2017 Wiley Periodicals, Inc.)

Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer. In the last decade, the development and approval of substances inhibiting the vicious cycle of bone metastases have enabled the reduction of complications caused by bone metastases in patients with castration-resistant prostate cancer. These drugs have raised awareness of the importance of skeletal-related events which in the meantime represent an important end point also in trials using agents not specifically designed for bone lesions. Second-generation antihormonal drugs such as enzalutamide or abiraterone have been shown to have a positive impact on the incidence of skeletal complications and therefore provide an important tool in the armamentarium used for treating bone metastases. Radiopharmaceuticals such as radium-223 dichloride ([223Ra]) have been demonstrated not only to reduce skeletal-related events and bone-related pain, but also to prolong overall survival, thereby being the first bone-targeting agent showing a survival benefit. As previous studies have not provided an obvious benefit of bone-targeted lesions in castration-sensitive disease, the use of these agents is not recommended. In oligometastatic prostate cancer, the role of local treatment of metastases using stereotactic radiation or radiosurgery is a matter of intense debates and may play an increasing role in the future.

Urinary bladder injury or malfunction may occur due to a variety of underlying diseases or trauma mechanisms. This review discusses surgical principles and approaches for urinary bladder reconstruction and function preservation., Competing Interests: Interessenkonflikte: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Circulating tumor cells (CTC) have become an important biomarker in patients with advanced prostate cancer. CTC count has been demonstrated to be a prognostic factor for overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). In localized prostate cancer, a clear correlation between CTC counts and clinicopathological risk parameters and outcome has not been observed. Currently, the focus of research is shifting from CTC enumeration towards molecular characterization of CTC leading to the discovery of markers predicting treatment response. The role of androgen receptor splice variants expressed by CTC as markers of resistance to abiraterone and enzalutamide has been assessed by various studies. The identification of CTC markers predicting treatment response represents a key step to guide the selection of treatment (e.g., abiraterone/enzalutamide vs taxanes), particularly in patients with mCRPC. As an alternative to CTC, the analysis of circulating tumor DNA has been shown to enable a noninvasive disease characterization having high potential to promote precision oncology.

Background/aim: Chronic periodontitis (CP) has already been associated with altered PSA values in men undergoing biopsy. This study addressed the impact of CP treatment on PSA screening., Patients and Methods: Fifty-two asymptomatic men presenting for CP treatment were prospectively enrolled. Total (t)PSA, free (f)PSA and %PSA were determined (n=47) before and after therapy. Pre- and post-therapy values were correlated pairwise regarding patients and dental characteristics., Results: Median age was 54 years (SD=±7.7 years) and mean tPSA was 1.3 ng/ml (±1.9 ng/ml). tPSA and fPSA correlated linearly and positively with age (p<0.002). After stratification by age, tPSA/fPSA remained significantly lower in smokers (p<0.05). No other patient or dental factor was associated with tPSA, fPSA, %PSA. CP therapy had no effect on PSA reduction and did not affect indication for biopsy., Conclusion: The potential influence of CP on PSA testing seems to be excludable in asymptomatic men., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To evaluate the Mayo Adhesive Probability (MAP) score, renal pelvis score, and RENAL nephrometry score for the prediction of surgical outcome in patients with renal masses undergoing laparoscopic partial nephrectomy at a single center., Patients and Methods: A total of 280 patients who underwent laparoscopic partial nephrectomy were identified retrospectively. Thirty-eight patients were excluded because of a lack of preoperative imaging. The outcome measures included surgical technique, patient characteristics, MAP score, renal-pelvis-score, RENAL nephrometry score, and complication rates according to the Clavien-Dindo classification. Regression analysis was performed for assessment of the predictive value of the given scores., Results: Complications occurred after 32 (13%) operations. There was a significant positive association between the development of complications and RENAL nephrometry score (p=0.003). Prediction of complications was improved by the RENAL nephrometry score [area under the curve (AUC) =0.675] and the MAP score (AUC=0.655): With an increasing MAP score, there was a significantly increased operative time (p=0.033). The renal pelvis score had a minor predicitive role (AUC=0.516) and no correlation was found with postoperative urine leakage., Conclusion: The MAP score and RENAL nephrometry score seem to be able to predict a complex or complicated intra- and postoperative course, while the renal pelvis score is not suitable for predicting postoperative complications, especially urine leakage., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To determine the differential expression patterns and prognostic relevance of Mucin-1 (MUC1) expression in clear cell renal cell carcinoma (RCC) metastasis., Methods: Tissue microarrays (TMA) from samples of 151 RCC metastases, 61 primary RCCs and corresponding benign renal tissues were immunohistochemically stained for MUC1 and semi-quantitatively evaluated by immunoreactivity scores (IRS). MUC1 differential expression in metastasis, primary RCC and normal tissue were comparatively analyzed. Patient characteristics and clinical follow-up for patients with metastatic RCC (mRCC) were recorded. Correlations of MUC1 expression with mRCC survival were determined., Results: Median cytoplasmic expression was highest in benign tissue (IRS = 1.04). Primary RCC (0.50) and metastasis (0.12) showed significantly lower cytoplasmic staining intensity. Membranous expression in benign tissue was, however, significantly lower (0.21) compared with primary RCC (0.59) and metastasis (0.57). Notable differences of MUC1 cytoplasmic and membranous expression were observed between different metastasis sites. Significantly higher (P = 0.014) membranous expression was observed in pulmonary versus non-pulmonary lesions, while no significant differences of cytoplasmic MUC1 expression were observed. The prognostic relevance of MUC1 expression in metastatic RCC was limited., Conclusions: MUC1 is differentially expressed in benign renal tissue, primary RCC and RCC metastasis. Membranous MUC1 expression was significantly elevated in pulmonary metastases compared to non-pulmonary lesions, which may reflect individual biology and putative response to MUC1-based anti-cancer therapy.

Aim: The aim of the study was to investigate the clinical impact of the surgical margin width after nephron-sparing surgery (NSS) on the oncological course of renal cell carcinoma (RCC)., Patients and Methods: The study comprised of 126 RCC patients with NSS between 2002 and 2009. Inclusion criteria were negative resection margins and a tumor diameter of ≤100 mm with the possibility of a complete circumferential histopathological reevaluation. The minimal benign margin width was correlated to the patients' clinical course., Results: Median safety margin width was revealed to be 1 mm. Nine of 126 patients (7.1%) developed recurrent disease (five local, four distant). All patients with local recurrence had safety margins ≤1 mm, whereas out of 49 patients with a margin >1 mm no one developed local recurrence (p=0.0245). Safety margin ≤1 mm showed associations with increased risk for overall recurrence in univariate and multivariate analysis (p=0.0531 and 0.0539, respectively)., Conclusion: Tumor adjacent renal parenchyma may have oncological relevance, corroborating the need for further molecular investigation of tumor-adjacent tissue in RCC., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: To determine the expression patterns of the proliferation marker prostate tumor overexpressed 1 (PTOV1) in invasive urothelial cancer (UC)., Methods: Corresponding UC and benign samples from paraffin-embedded tissue of 102 patients treated with cystectomy for invasive UC were immunohistochemically (IHC) assessed for PTOV1. Expression was evaluated gradually separated for cytoplasmic and nuclear staining. Results were correlated to histological and clinical data. To correlate PTOV1 expression with molecular subtypes of UC, analysis of PTOV1 RNA expression data of the Cancer Genome Atlas UC cohort was performed., Results: PTOV1 expression was present in UC and benign urothelium, whereby nuclear staining was significantly more frequent in UC tissue (p = 0.0004). Lower cytoplasmic expression was significantly associated with pathological stage >pT2 (p = 0.0014) and grade ≥G3 (p = 0.0041), respectively. IHC expression patterns did not show correlation to survival data. PTOV1 RNA expression correlated with features of the luminal UC subtype., Conclusions: Subcellular distribution seems to be the most important feature of PTOV1 expression in UC. Nuclear localization of PTOV1 along with cytoplasmic decrease in PTOV1 expression was identified as putative surrogate for PTOV1-associated cellular proliferation and dedifferentiation in UC. The functional relevance as well as the potential role of PTOV1 as a biomarker in UC remains to be specified in future studies.

Purpose: To evaluate the influence of preoperative patient-associated parameters and comorbidities, with special focus on preoperative renal function on non-muscle-invasive bladder carcinoma (NMIBC) recurrence and progression., Patients and Methods: Medical records of 192 patients with first diagnosis of NMIBC from 1996 to 2006 treated at our department were reviewed for tumor stage and grade, comorbidities, and putative preoperative risk factors (diabetes mellitus, smoking habits, C-reactive protein levels, estimated glomerular filtration rate [eGFR] by chronic kidney disease-epidemiology collaboration formula, patient age, and sex)., Results: Median follow-up was 80 months. Tumor recurrence was observed in 104 patients (54%); progression to higher pT category or grade was found in 43 patients (22%). Overall, 20 (10%) patients had progression to category pT2, with a median time to progression of 11 months (95% CI: 3.16-55.77). Overall, median time to recurrence was 11.91 months (8.00-14.94), while median time to progression to higher category/grade was 15 months (8.60-36.95). Cancer-specific death was recorded for 12 patients (6%). Univariate analysis revealed category, grade, and eGFR < 60 ml/min as significant predictive determinants for recurrence, overall progression, and progression to pT2-category disease. Based on the results of multivariate analysis, a risk factor model was created to classify patients with high and low risk of recurrence., Conclusions: eGFR is a significant predictive variable of NMIBC recurrence and progression. Integrating eGFR into NMIBC risk calculation helped to discriminate individuals with high and low risk of cancer recurrence. Confirmatory studies and external validation are needed to corroborate these findings. Furthermore, the role of tumor multifocality and size should be analyzed for the proposed prediction model., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Ileal ureter is a suitable treatment option for patients with long ureteric strictures. Minimally invasive techniques have been shown to be as safe as open techniques but superior in terms of post-operative recovery. We report our experience using minimally invasive techniques for total intracorporeal ureteral replacement., Material and Methods: A chart review revealed five patients who underwent intracorporeal ileal ureter using minimally invasive techniques in the preceding 5 years. 4 patients underwent conventional laparoscopic surgery and 1 patient underwent robotic-assisted surgery. Patient's characteristics, perioperative data and functional outcomes as well as a detailed description of surgical technique are reported. In all 5 of these patients, the ileal ureter was performed completely intracorporeally., Results: The median age of our patients is 61 (range 42-73). The median operative time was 250 minutes (range 150-320) and median blood loss was 100 ml (range 50-200). The median hospital stay was 8 days (range 6-10) and there were no major perioperative complications reported. At median follow up of 22 months (range 4-38), there were no recurrences of strictures or any other complications., Conclusions: We have demonstrated the safety and feasibility of minimally invasive intracorporeal ileal ureter. Numbers are still small but its application is likely to grow further.

Introduction: We evaluated the success rate of continent vesicostomy using an ileal segment with seroserosally embedded, tapered ileum for bladder augmentation with continent stoma following bladder neck closure (BNC) for severely damaged bladders or persistent urinary incontinence., Material and Methods: A total of 15 patients were treated for persistent urinary incontinence or non-reconstructible bladder outlet between 2003 and 2012. Underlying diagnosis included post-prostatectomy incontinence (n = 5), recurrent bladder neck stenosis (n = 5), neurogenic bladder (n = 3), urethral tumor recurrence following orthotopic neobladder (n = 1) and post-TVT and colposuspension incontinence (n = 1). All patients underwent open BNC, omental interposition and continent vesicoileostomy. The continent outlet was placed in the lower abdomen using a circumferential subcutaneous and skin plasty to avoid retraction. Data collected included age, underlying diagnosis, stoma site, time to complications and need for subsequent surgical revisions. All patients received a standardized questionnaire at the time of data acquisition and were personally interviewed., Results: Median follow-up was 24 months (range: 2-111). Primary BNC was successful in all patients and primary continence rate was 86.7%. Two patients (13.3%) suffered from failure of the continence mechanism, caused by stoma stenosis at skin level and insufficiency of the bladder augmentation and stoma due to local infection. One additional patient developed a mild stomal incontinence without need for further reconstruction. Regardless of the number of revisions, at the last follow-up 93.3% of patients had a functional channel. All complications occurred within the first postoperative year., Conclusions: This technique is an effective last resort treatment for patients with non-reconstructible bladder outlet.

Background: The growing use of alpha-1 receptor antagonists in the treatment of benign prostatic hyperplasia (BPH) has created a new problem in ophthalmic surgery, the so-called intraoperative floppy iris syndrome (IFIS). This consists of a billowing iris, insufficient pupillary dilation with progressive intraoperative miosis, and protrusion of iris tissue through the tunnel and side port incision that are made for access to the anterior chamber during surgery. IFIS presents particular difficulties in cataract surgery which is carried out through the pupil with manipulations in the immediate vicinity of the iris. The complications range from poor visibility of the operative field to iris damage with the surgical instruments and to rupture of the posterior capsule, with loss of lens material into the vitreous body., Methods: Selective literature review., Results: Alpha-blockers have a direct effect on the alpha-receptors of the iris but also induce ultrastructural changes in the iridial stroma, leading to IFIS. The most important factor in avoiding complications of IFIS seems to be the ophthalmic surgeon's knowledge that the patient is taking an alpha-1 receptor antagonist., Conclusion: A thorough medical history and an optimized information flow among all physicians treating the patient-the urologist, the family physician, and the ophthalmic surgeon-are essential for safe cataract surgery.