[Current guideline-oriented follow-up of small renal masses : Applied risk scores and future outlook]. / Aktuelle leitliniengerechte Nachsorge kleiner Nierentumoren : Angewandte Risikoscores und Zukunftsausblick.

After surgical resection of renal cell carcinoma by laparoscopic or open partial or complete nephrectomy, medical aftercare based on the current guidelines should be provided. This seems desirable, especially because one third of patients after initial curative tumor resection develop recurrence over time. In this article, the current recommendations for follow-up will be systematically presented based on the accepted German S3 guideline and the European Association of Urology (EAU) guideline. Another point of this article will be the presentation of the currently applied risk scores to predict prognosis with a focus on molecular markers. The goal is to improve the prediction of survival and to facilitate risk-adjusted aftercare.

[TKI 2.0 - changes in the medical treatment of renal cell carcinoma]. / TKI 2.0 ­ Wandel in der medikamentösen Therapie des Nierenzellkarzinoms.

Only for renal cell carcinoma (RCC) in a local stage curative treatment option by surgical resection exists. For metastatic disease the 5­year survival rate decreases radically. A factor that contributes to this is the low sensibility to radiation and chemotherapeutics. Since the approval of the tyrosine kinase inhibitors in 2006 effective drugs for the treatment of mRCC is available. The specific inhibition of the vascular-endothelial-growth (VEGF)-receptor and the "mammalian Target of Rapamycin" (mTOR) leads to a prolongation of the progression-free survival as well as the overall survival rate. For a long time, the current target therapy with TKI appeared to be exhausted, but since recently research has gone a step further. Thus, Cabozantinib and Lenvatinib in the combination with Everolimus have been approved for second-line therapy in mRCC. For the first time a clinical study demonstrated positive results for an adjuvant treatment with sunitinib in patients with a high-risk RCC. Furthermore, in april 2016 the immune checkpoint inhibitor Nivolumab was approved for second-line therapy in mRCC in Germany. The following report examines briefly the current therapeutic recommendations, new findings and drug approvals and ongoing clinical trials.

First report of robot-assisted transperineal fusion versus off-target biopsy in patients undergoing repeat prostate biopsy.

PURPOSE: To clarify the value of targeted versus off-target biopsies in men with a suspicion of prostate cancer (PC) and a visible lesion in multi-parametric magnetic resonance imaging (mpMRI) using transperineal robot-assisted biopsy. METHODS: Fifty-five consecutive men with one non-palpable suspicious lesion in mpMRI after negative 12-core transrectal ultrasound-guided biopsy were enrolled in 2014-2015. Lesions were scored using the Prostate Imaging Reporting and Data System. A robot-assisted system was utilized to collect four robot-assisted targeted transperineal biopsy cores (RA-TB) within the lesion using mpMRI-TRUS elastic fusion. Untargeted transperineal 14-core biopsy was performed only outside the lesion (RA-UB). Histological grade was compared in biopsies and available prostatectomy specimens. RESULTS: Overall, 34 of 55 patients (62%) were diagnosed with PC based on biopsy. 85% of cancers were clinically significant PC (csPC) defined as GS ≥ 7. 85% of biopsy-proven cancers were detected with RA-TB alone. RA-UB identified only one additional patient with csPC and lead to upgrading in five biopsy cases (14.7%). Pathological evaluation of 14 prostatectomy specimens showed upgrading in 2 patients (14.3%), while all other patients were correctly classified by RA-TB without need of additional RA-UB. Mean procedure duration was 43 (±6) min, and only minor complications according to Clavien-Dindo were recorded during 30-day follow-up. CONCLUSIONS: This is the first report of transperineal robot-assisted elastic mpMRI-TRUS fusion biopsy. RA-TB of positive MR lesions enabled reliable detection of csPC, while RA-UB in MRI-negative regions is of minor importance.

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy]. / MRT/TRUS-fusionierte Biopsiesysteme : Stellenwert bei der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. OBJECTIVES: Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. MATERIALS AND METHODS: A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). RESULTS: Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. DISCUSSION: Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). CONCLUSIONS: There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

Prostate cancer gene 3 (PCA3) is of additional predictive value in patients with PI-RADS grade III (intermediate) lesions in the MR-guided re-biopsy setting for prostate cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) improves diagnostic accuracy in re-biopsies of men with prostate cancer (PC) suspicion, but predictive value is limited despite the use of the new Prostate Imaging Reporting and Data System (PI-RADS). Prognostic value of the PC-specific biomarker prostate cancer gene 3 (PCA3) added to the PI-RADS score was evaluated. METHODS: The study was a retrospective analysis of the institutional database for men with MR-guided biopsy (MR-GB) for suspicious lesion in mpMRI and who had an additional pre-MR-GB PCA3 testing for ongoing PC suspicion. All men had ≥ 1 negative ultrasound GB. Lesions were retrospectively scored by PI-RADS in three MRI sequences (T2w, DCE, and DWI). PCA3 was analyzed with cutoffs of 25 and 35. The prognostic value of mpMRI and PCA3 and the additional value of both were explored. RESULTS: Tumor detection rate (49 men, mean PSA 10 ng/ml, lesion size 40 mm(2)) was 45 % (22/49 patients). In the subgroup of PI-RADS IV°, 17/17 patients had PC; in PI-RADS III° (intermediate) 5/15 had PC, and all 5 had a PCA3 > 35. PCA3 > 35 had no additional prognostic value in the whole cohort. Out of the 10/15 PC negative patients (PI-RADS III°), PCA3 was < 35 in 6. The inclusion of PCA3 value in PI-RADS III° patients improved predictive accuracy to 91.8 %. CONCLUSION: MpMRI and subsequent grading to PI-RADS significantly improves PC detection in the re-biopsy setting. The diagnostic uncertainty in the PI-RADS intermediate group can be ameliorated by the addition of PCA3 cutoff of 35 to avoid potential unnecessary biopsies.

Influence of body mass index, surgical approach and lymphadenectomy on the development of symptomatic lymphoceles after radical prostatectomy.

PURPOSE: Identification of factors influencing lymphocele formation requiring intervention after radical prostatectomy. METHODS: 302 patients undergoing radical retropubic prostatectomy (RRP, n = 174) or transperitoneal robot-assisted laparoscopic prostatectomy (RALP, n = 128) by the same surgeon were retrospectively reviewed. Incidence of symptomatic lymphoceles (SLC) was compared with clinical and pathological data (contingency analyses, Wilcoxon-Kruskal-Wallis test). RESULTS: Sixteen patients (5.3%) developed SLC. SLC occurred significantly more frequently after RRP compared to RALP (8.0 vs. 0.8%, p = 0.0008). Patients with SLC had more lymph nodes (LN) removed median (17 vs. 13, p = 0.009) and a significantly lower BMI (median 24.4 vs. 26.4, p = 0.0008). Presence of LN metastases (n = 18 patients, 6.0%) showed no statistical impact on SLC. In a multivariate analysis surgical method, the number of resected LN and the BMI remained independent predictors of SLC formation. CONCLUSIONS: The lower incidence of SLC after RALP compared to RRP probably results from peritoneal drainage of lymphatic fluid. The correlation of removed LN and SLC might be explained by increased injury of lymphatic vessels during more extended LN dissection. Why patients with lower BMI are more prone to develop SLC still remains unclear. However, early postoperative mobilization in nonobese patients might be a contributing factor.

[Urinary incontinence in the elderly: what can and should be done?]. / Inkontinenz im Alter: Was kann und soll man tun?

The demographic development of society shows a clear increase in the elderly population in the coming decades, which will result in an increasing prevalence of urinary incontinence. Diagnosis and treatment of many patients is not carried out for a myriad of reasons and thus incontinence care is often inadequate. A detailed medical history is the basis of identification of the problem and underpins the effective diagnostic and therapeutic management of the problem. In this context, the algorithms based on the national and international guidelines and age-specific characteristics should be considered. The initial focus should be on conservative management. In a few cases of elderly patients, invasive diagnostics using urodynamics or cystoscopy might be indicated. The increased use of medication in the elderly both from an etiological and therapeutic point of view, especially in terms of drug/drug interactions requires special consideration. In particular cognitive impairment using pharmacological approaches should be avoided. Although incontinence surgery of the patient applies less often with increasing age it still plays a role in the appropriate selection of treatment.

Different surgical approaches for stress urinary incontinence in women.

Stress urinary incontinence (SUI) constitutes involuntary voiding as a consequence of rising intra-abdominal pressure caused by sphincter weakness. In recent years studies were published according to surgical SUI management evaluating and comparing therapy options and outcomes. Therapy options were evaluated using a Medline search, including only publications in English between 2000-2012. Key words used were: SUI, conservative and surgical treatment, midurethral sling, colposuspension. Surgical treatment options demonstrate significantly better results than conservative treatment. MUS demonstrate better subjective and objective cure rates than colposuspension; it is less invasive and more cost-effective. First line SUI therapy such as RP MUS and TVT seem to be favored when compared to transobturator techniques. Retropubic and transobturator MUS showed equivalent objective and subjective success rates. Open colposuspension is an effective treatment possibility for recurrent SUI after failed MUS. TVT, compared with other MUS, seems to show slightly better cure rates. but perioperative complications appear to be similar. Long-term results (>10 years) of repeated SUI surgery showed that the Burch procedure had the lowest 9-year cumulative incidence of repeat SUI surgery. Mini-sling techniques may be underestimated but long-time results are pending and closer monitoring of the adverse event profile must be carried out. MUS are first choice in the treatment of SUI, of which TVT, has the best cure rate. Colpussupension continues to have its place in recurrent SUI. The new mini-MUS needs a longer follow-up for final evaluation.

Human pregnane X receptor genotype of the donor but not of the recipient is a risk factor for delayed graft function after renal transplantation.

Delayed graft function (DGF) is an important complication in renal transplantation, contributing significantly to decrease in long-term allograft survival. In addition to donor- and recipient-related risk factors such as immunosuppression, altered renal excretion of xenobiotics by membrane transporters may influence DGF. Using DNA samples from recipients and donors, we assessed the impact on DGF of genetic variants in P-glycoprotein (ABCB1), multidrug resistance protein 2 (ABCC2), and the nuclear pregnane X receptor (PXR/NR1I2), which regulates the transcription of enzymes and transporters. In our local cohort of renal transplant recipients (n = 178), DGF occurred in 27.5%. The PXR 8055TT genotype of the donor only (not of the recipient) was significantly associated with an increased risk for DGF. This finding emerged from univariate as well as multivariate logistic regression analysis including 16 nongenetic factors and held true after correction for multiple testing. Our findings provide the first evidence that PXR may be associated with risk of DGF, independent of previously identified risk factors.

MRI-guided prostate biopsy detects clinically significant cancer: analysis of a cohort of 100 patients after previous negative TRUS biopsy.

PURPOSE: To investigate the positive biopsy rate of MRI-guided biopsy (MR-GB) in a routine clinical setting, identify factors predictive for positive biopsy findings and to report about the clinical significance of the diagnosed tumors. METHODS: Patients with at least one negative trans-rectal-ultrasound-guided biopsy (TRUS-GB), persistently elevated or rising serum prostate specific antigen (PSA) and at least one lesion suspicious for PCa on diagnostic 1.5 Tesla endorectal coil MRI (eMR) were included. Biopsies were carried out using a 1.5 Tesla MRI and an 18 G biopsy gun. Clinical information and biopsy results were collected; logistic regression analysis was carried out. Definite pathology reports of patients with diagnosis of PCa and subsequent radical prostatectomy (RP) were analyzed for criteria of clinical significance. RESULTS: One hundred patients were included, mean number of previous biopsies was 2 (range 1-9), mean PSA at time of biopsy was 11.7 ng/ml (1.0-65.0), and mean prostate volume was 46.7 ccm (range 13-183). In 52/100 (52.0%) patients, PCa was detected. Out of 52 patients, 27 patients with a positive biopsy underwent RP, 20 patients radiation therapy, and 5 patients active surveillance. In total, 80.8% of the patients revealed a clinically significant PCa. In univariate regression analysis, only serum PSA levels were predictive for a positive biopsy result. Number of preceding negative biopsies was not associated with the likelihood of a positive biopsy result. CONCLUSIONS: MR-GB shows a high detection rate of clinically significant PCa in patients with previous negative TRUS-GB and persisting suspicion for PCa.

Kidney-specific cadherin correlates with the ontogenetic origin of renal cell carcinoma subtypes: an indicator of a malignant potential?

INTRODUCTION AND OBJECTIVES: To evaluate retrospectively kidney-specific cadherin (Ksp-cad) expression in renal cell carcinoma (RCC) subtypes and oncocytoma in correlation with its ontogenetic origin of distal and proximal tubules and to correlate Ksp-cad expression with tumour characteristics. MATERIALS AND METHODS: Membranous and cytoplasmic expression of Ksp-cad was determined in 40 clear cell (ccRCC), 25 papillary (pRCC), 19 chromophobe carcinomas (chRCC), 27 oncocytomas (oncocytomas) (n = 111) and 32 benign kidney parenchyma specimens separated in distal tubules (DT) and proximal tubules (PT) by immunohistochemistry using tissue microarray technique. Staining intensity was quantified as a score ranging from 0 to 12. Comparison of data and correlation with tumour characteristics were done by Wilcoxon/Kruskal-Wallis tests (post hoc Tukey-Kramer analysis). RESULTS: In benign renal tissue, membranous and cytoplasmic expression of Ksp-cad in the DT was significantly higher than that in the PT (12.0 ± 0 vs. 5.2 ± 0.3 and 6.3 ± 0.5 vs. 0.0 ± 0.0, respectively; (P < 0.05)). Membranous KSP-cad expression was significantly higher in chRCC (5.2 ± 0.8) and oncocytomas (3.7 ± 0.4) than that in ccRCC (0.8 ± 0.2) and pRCC (1.4 ± 0.4; P < 0.05), while expression between oncocytomas and chRCC did not differ significantly. In RCC, Ksp-cad expression was significantly associated with higher T stage and the occurrence of synchronous metastasis (P < 0.05). Higher N stages and grading tended to correlate with a lower Ksp-cad expression. CONCLUSIONS: In this cohort, the origin of tumour subtypes-chRCC and oncocytomas develop from DT and ccRCC and pRCC from PT cells-is mirrored by the respective Ksp-cad expression. This raises the question whether DT-derived tumours have a less malignant potential than PT-derived tumours.

Akt signalling parameters are different in oncocytomas compared to renal cell carcinoma.

PURPOSE: Renal oncocytomas are assigned as benign tumours, and their detailed molecular mechanism is poorly characterised. Activation of the PKB/Akt pathway is assumed to contribute to the pathogenesis and progression of malignant disease. For oncocytomas, hardly any data are available for Akt signalling parameters. Aim of the present work was to determine the alterations of Akt parameters PTEN, phosphorylated Akt (p-Akt) and p27(Kip1) in oncocytoma to better understand the dedifferentiation of renal tumours. METHODS: By tissue microarray analysis 15 oncocytoma, 18 clear cell renal cell carcinoma (ccRCC) and the corresponding benign tissue were investigated. Significant expression differences between PTEN, p-Akt and p27(Kip1) were determined by immunohistochemistry using One-way ANOVA with all pairs Tukey-Kramer as post hoc analyses. To investigate Akt parameter interactions in the oncocytoma, linear regression analyses were performed. RESULTS: Expression of all proteins was significantly different between the groups and in all groups the lowest for oncocytoma: PTEN: 32.9 ± 13.0 versus 75.5 ± 8.0 versus 123.7 ± 8.8; p < 0.001 for oncocytoma, benign parenchyma and ccRCC and 2.7 ± 1.2 versus 40.8 ± 9.5 versus 143.6 ± 12.2; p < 0.001 for p27(Kip1). p-Akt expression was significantly different between oncocytoma and ccRCC (67.3 ± 15.7 vs. 144.0 ± 26.6; p < 0.05). CONCLUSION: All three investigated parameters were the lowest in oncocytoma when compared to ccRCC. Expression of PTEN and p27(Kip1) seems to be exceedingly associated with malignant conditions of ccRCC. These findings might contribute to the understanding of tumorous signalling of the PKB/Akt axis in renal tumours.

Top-down modulation of auditory processing: effects of sound context, musical expertise and attentional focus.

By recording auditory electrical brain potentials, we investigated whether the basic sound parameters (frequency, duration and intensity) are differentially encoded among speech vs. music sounds by musicians and non-musicians during different attentional demands. To this end, a pseudoword and an instrumental sound of comparable frequency and duration were presented. The accuracy of neural discrimination was tested by manipulations of frequency, duration and intensity. Additionally, the subjects' attentional focus was manipulated by instructions to ignore the sounds while watching a silent movie or to attentively discriminate the different sounds. In both musicians and non-musicians, the pre-attentively evoked mismatch negativity (MMN) component was larger to slight changes in music than in speech sounds. The MMN was also larger to intensity changes in music sounds and to duration changes in speech sounds. During attentional listening, all subjects more readily discriminated changes among speech sounds than among music sounds as indexed by the N2b response strength. Furthermore, during attentional listening, musicians displayed larger MMN and N2b than non-musicians for both music and speech sounds. Taken together, the data indicate that the discriminative abilities in human audition differ between music and speech sounds as a function of the sound-change context and the subjective familiarity of the sound parameters. These findings provide clear evidence for top-down modulatory effects in audition. In other words, the processing of sounds is realized by a dynamically adapting network considering type of sound, expertise and attentional demands, rather than by a strictly modularly organized stimulus-driven system.

Economic aspects of bladder cancer: what are the benefits and costs?

OBJECTIVE: Bladder cancer (BC) has the highest lifetime treatment costs per patient of all cancers. The high recurrence rate and ongoing invasive monitoring requirement are the key contributors to the economic and human toll of this disease. The purpose of this paper was to utilize the recent literature to identify opportunities for improving the benefits and costs of BC care. METHODS: A PubMed search was performed of recent publications concerning (BC) cost-effectiveness. We reviewed studies, reviews, opinion papers and cost-effectiveness analyses, focusing primarily on non-muscle-invasive bladder cancer (Ta/T1; NMIBC). RESULTS: New diagnostic tools such as urine markers may assist in more cost-effectively detecting BC at an earlier stage, however, these markers cannot replace the cystoscopy, which is the current standard of care. A photodynamic diagnostic tool (PDD) using hexylaminolevulinate (Hexvix) enhances tumor visibility and improves transurethral resection of bladder cancer (TURB) results, potentially reducing recurrence rates and lowering treatment costs. While the importance of BC research has been acknowledged, research investment has been continuously reduced during the last 5 years. CONCLUSIONS: The economic burden of BC is well-characterized in the literature. This study suggests that new technologies (i.e., urine-based tests, PDD) and therapeutic regimes (intravesical chemotherapy, adjuvant immunotherapy) have significant potential to improve the diagnosis, treatment and on-going monitoring of BC patients, with potential improvements in clinical outcomes and concurrent cost-savings. A renewed interest and investment in BC research are required to ensure future advancements.

[Somatostatin analogs for the treatment of advanced, hormone-refractory prostate cancer: a possibility for secondary hormonal ablation?]. / Somatostatin-Analoga in der Therapie des fortgeschrittenen hormonrefraktären Prostatakarzinoms: Eine Möglichkeit der sekundären Hormonablation?

Almost all patients with hormone-refractory prostate cancer under primary androgen deprivation therapy will develop progression, frequently initially marked by an asymptomatic increase of prostate-specific antigen (PSA). Recent data showed that taxane-based chemotherapy offers significant survival benefit to patients with advanced prostate cancer; however, the toxic side effects frequently exert a significant negative impact on the quality of life. At the androgen-independent stage of the cancer, before becoming hormone refractory, progression might still be delayed by secondary manipulation of either androgen or confounding receptors and their signaling pathways. Secondary hormonal manipulations traditionally included antiandrogen withdrawal, second-line antiandrogens, direct adrenal androgen inhibitors, estrogens, and progestins.We discuss the mode of action and application of somatostatin analogs as an emerging secondary hormonal treatment concept in patients with advanced prostate cancer on the basis of the current literature.

[Efficacy of multikinase inhibitors in the treatment of advanced renal cell cancer. A snapshot]. / Wirksamkeit von Multikinaseinhibitoren in der Therapie des fortgeschrittenen Nierenzellkarzinoms. Eine Momentaufnahme.

Due to the chemoresistance of renal cell cancer, cytokine-based therapeutic approaches were considered the standard treatment for patients with metastatic disease. At present, data that are available from a few phase II/III studies, dealing both with the first- and second-line treatment of patients suffering from systemic progression of RCC, indicate the significantly higher clinical efficacy of multikinase inhibitors when compared with cytokine-based therapeutic regimens. In this context, sorafenib (Nexavar, BAY 43-9006) and sunitinib (Sutent, SU 011248) are the most frequently applied and most intensively investigated substances. In Germany, with regard to a phase III study reported at the ASCO congress in 2006, sunitinib received approval for the first-line therapy of metastatic RCC. The application of multikinase inhibitors follows the principle of targeting such mediators that are considered to be substantially involved in the pathogenesis and particularly progression of renal cell cancer within relatively well-defined molecular pathways. The aim of the present paper is to address and to critically discuss the clinical data that are currently available regarding the therapeutic efficacy of kinase inhibitors during the treatment of metastatic RCC.