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Purpose: The death ligand tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-R) are involved in immune surveillance and tumor development. Here, we studied a possible association between the expression of TRAIL/TRAIL-Rs and the prognosis in patients with renal cell carcinomas (RCC).Experimental Design: A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples from 838 patients was generated. Expression of TRAIL and TRAIL-Rs was examined by immunohistochemistry and the effect of TRAIL and TRAIL-R expression on disease-specific survival was assessed.Results: High TRAIL-R2 expression levels were associated with high-grade RCCs (P < 0.001) and correlated negatively with disease-specific survival (P = 0.01). Similarly, high TRAIL expression was associated with a shorter disease-specific survival (P = 0.01). In contrast, low TRAIL-R4 expression was associated with high-stage RCCs (P < 0.001) as well as with the incidence of distant metastasis (P = 0.03) and correlated negatively with disease-specific survival (P = 0.02). In patients without distant metastasis, multivariate Cox regression analyses revealed that TRAIL-R2 and TRAIL are independent prognostic factors for cancer-specific survival (in addition to tumor extent, regional lymph node metastasis, grade of malignancy, and type of surgery).Conclusion: High TRAIL-R2, high TRAIL, and low TRAIL-R4 expression levels are associated with a worse disease-specific survival in patients with RCCs. Therefore, the assessment of TRAIL/TRAIL-R expression offers valuable prognostic information that could be used to select patients for adjuvant therapy studies. Moreover, our findings are of relevance for a potential experimental therapeutic administration of TRAIL-R agonists in patients with RCCs.

Supplementary Data from Prognostic Value of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) and TRAIL Receptors in Renal Cell Cancer

OBJECTIVES: To compare the operative and functional result of partial and radical nephrectomy in renal cell carcinomas of stages pT2-3a. METHODS: Consecutive patients with renal cell carcinoma of stages pT2-3a, cN0 and cM0, who underwent partial or radical nephrectomy between January 2005 and October 2019 at a tertiary care center were included. Data were collected retrospectively. End-points included severe postoperative complications (Clavien-Dindo classification ≥3), acute and chronic renal function impairment, and overall survival. Uni- and multivariable outcome analyses were based on logistic regression. RESULTS: A total of 158 patients were included (110 radical nephrectomy and 48 partial nephrectomy). Over time, partial nephrectomy was increasingly used. A RENAL score ≥10 was the only independent predictor influencing the surgical approach (radical nephrectomy vs partial nephrectomy, odds ratio 8.62, 95% confidence interval 3.32-22.37, P

Zusammenfassung Hintergrund Urologische OberärztInnen in Deutschland stellen eine heterogene Berufsgruppe mit verschiedenen klinischen Schwerpunkten und Karriereabsichten dar. Bisher gibt es keine gesicherten Kenntnisse darüber, welchen Einfluss die Anzahl der Berufsjahre in dieser Position auf die aktuelle Berufsausübung und Zufriedenheit hat. Material und Methoden Ziel der vorliegenden Studie war die vergleichende Analyse der berufsbezogenen Sichtweisen, des privaten und beruflichen Umfelds, der konkreten Tätigkeiten und der fachlichen Zielvorstellungen urologischer OberärztInnen in Deutschland anhand der Anzahl der Berufsjahre in dieser Position (Dichotomisierung bei 8 Jahren Oberarzttätigkeit). Im Rahmen einer Querschnittsstudie wurde ein 55 Items umfassender, webbasierter Fragebogen entwickelt, der als Link über den E-Mail-Verteiler der Deutschen Gesellschaft für Urologie versendet wurde und zwischen Februar und April 2019 für urologische OberärztInnen geöffnet war. Unterschiede zwischen beiden Gruppen wurden mittels multivariater Regressionsmodelle geprüft. Ergebnisse 192 Studienfragebögen urologischer OberärztInnen waren auswertbar, von denen 107 (55,7 %) und 85 (44,3 %) eine Oberarzttätigkeit Schlussfolgerung Die vorliegende Studie zeigt deutliche Unterschiede bez. der operativen Fertigkeiten in Abhängigkeit von der Dauer der bisherigen OA-Tätigkeit. Außerdem wird eine erhebliche Unzufriedenheit mit der Förderung von Führungsqualitäten und der Vorbereitung auf Führungsaufgaben deutlich. Um qualifiziertes Personal langfristig als urologische OberärztInnen an den Kliniken im Fach Urologie zu binden, erscheint es notwendig, die Bedürfnisse der Berufsgruppe zu berücksichtigen und Defizite durch strategische Förderungen zu beheben.

Introduction: The aim was to evaluate the impact of perioperative blood transfusions (PBTs) on renal function after surgery for renal cell carcinoma (RCC). Methods: Consecutive patients with RCC who underwent partial nephrectomy or radical nephrectomy between 2005 and 2015 at a tertiary care center were included. Minimum follow-up period was 6 months. A PBT was defined as the transfusion of packed erythrocyte concentrate (EC) within 7 days before until 30 days after surgery. The multivariable analyses were carried out by Cox regression. Results: The overall cohort included 851 patients, of whom 93 (10.9%) received a PBT. The median follow-up was 46 months (range 28–72). In case of a PBT, a median of 2 EC was transfused. PBT patients were older and had a poorer performance status and more comorbidities as well as locally more advanced or metastatic tumors. In the multivariable analyses, PBT was an independent prognostic factor for acute as well as chronic renal impairment (hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.45–5.10, p = 0.002 and HR 2.23, 95% CI 1.26–3.70, p = 0.007). Conclusion: PBT is associated with acute and chronic deterioration of kidney function after surgery for RCC. Thus, it may be used to identify patients requiring close nephrological monitoring.

Purpose To examine frailty and comorbidity as predictors of outcome of nephron sparing surgery (NSS) and as decision tools for identifying candidates for active surveillance (AS) or tumor ablation (TA). Methods Frailty and comorbidity were assessed using the modified frailty index of the Canadian Study of Health and Aging (11-CSHA) and the age-adjusted Charlson-Comorbidity Index (aaCCI) as well as albumin and the radiological skeletal-muscle-index (SMI) in a cohort of n = 447 patients with localized renal masses. Renal tumor anatomy was classified according to the RENAL nephrometry system. Regression analyses were performed to assess predictors of surgical outcome of patients undergoing NSS as well as to identify possible influencing factors of patients undergoing alternative therapies (AS/TA). Results Overall 409 patient underwent NSS while 38 received AS or TA. Patients undergoing TA/AS were more likely to be frail or comorbid compared to patients undergoing NSS (aaCCI: p p = 0.001) and hospital re-admission (aaCCI ≥ 6: OR = 4.93, p = 0.003) in the NSS cohort. No impact was found for albumin levels and SMI. An aaCCI > 6 and/or 11-CSHA ≥ 0.27 (OR = 9.19, p p = 0.005) and hypoalbuminemia (OR = 4.6, p = 0.009), but not tumor complexity, were decisive factors to undergo AS or TA rather than NSS. Conclusion In patients with localized renal masses, frailty and comorbidity indices can be useful to predict surgical outcome and support decision-making towards AS or TA.

Urological senior physicians in Germany are a heterogeneous group with various clinical priorities and career objectives. To date, there are no reliable data concerning the impact of the time span for which senior physicians have been holding their position on professional, personal and position-linked aspects.The objective of this study was a comparative analysis of perspectives, private and professional settings, specific job-related activities and individual professional goals of urological senior physicians in Germany based on their experience in this position assessed as number of years (dichotomised at 8 years as senior physician). As part of a cross-sectional study, a 55-item web-based questionnaire was designed, which was sent via a link to members of a mailing list of the German Society of Urology. The survey was available for urological senior physicians between February and April 2019. Group differences were evaluated using multivariate regression models.107 of 192 evaluable questionnaires were completed by senior physicians holding this position for less than 8 years ( 8y senior physicians), 85 were completed by senior physicians holding this position for at least 8 years (≥ 8y senior physicians). 8y senior physicians worked significantly more often at university hospitals (42.1 % vs. 18.8 %, p = 0.002). Overall, 82.4 % of ≥ 8y senior physicians assessed themselves autonomously safe in performing open surgery, compared to 39.3 % among 8y senior physicians (p 0.001). No significant differences concerning the self-assessment were found for endourological procedures (94.1 % vs. 87.9 %) and for the overall lower-rated self-assessment concerning laparoscopy (29.4 % vs. 20.6 %) and robotic surgery (14.1 % vs. 10.3 %). Despite the high management responsibility associated with their position, only about one third of participants (34.8 %) had received specific postgraduate education preparing them for managing and executive tasks.This study shows significant differences among senior physicians regarding surgical skills depending on the time span they hold their position. Moreover, there is considerable dissatisfaction regarding the development of leadership skills and the preparation for managing tasks. In order to ensure availability of senior staff members for the field of urology in the future, it is important to consider their professional needs and to overcome existing shortcomings by education programs within well-orchestrated human resources development strategies.Urologische OberärztInnen in Deutschland stellen eine heterogene Berufsgruppe mit verschiedenen klinischen Schwerpunkten und Karriereabsichten dar. Bisher gibt es keine gesicherten Kenntnisse darüber, welchen Einfluss die Anzahl der Berufsjahre in dieser Position auf die aktuelle Berufsausübung und Zufriedenheit hat.Ziel der vorliegenden Studie war die vergleichende Analyse der berufsbezogenen Sichtweisen, des privaten und beruflichen Umfelds, der konkreten Tätigkeiten und der fachlichen Zielvorstellungen urologischer OberärztInnen in Deutschland anhand der Anzahl der Berufsjahre in dieser Position (Dichotomisierung bei 8 Jahren Oberarzttätigkeit). Im Rahmen einer Querschnittsstudie wurde ein 55 Items umfassender, webbasierter Fragebogen entwickelt, der als Link über den E-Mail-Verteiler der Deutschen Gesellschaft für Urologie versendet wurde und zwischen Februar und April 2019 für urologische OberärztInnen geöffnet war. Unterschiede zwischen beiden Gruppen wurden mittels multivariater Regressionsmodelle geprüft.192 Studienfragebögen urologischer OberärztInnen waren auswertbar, von denen 107 (55,7 %) und 85 (44,3 %) eine Oberarzttätigkeit 8 Jahre ( 8J-OÄ) bzw. ≥ 8 Jahre (≥ 8J-OÄ) aufwiesen. In der Gruppe 8J-OÄ arbeiteten signifikant mehr Teilnehmer an Universitätskliniken (42,1 % vs. 18,8 %, p = 0,002). Insgesamt gaben 82,4 % der Teilnehmer in der Gruppe ≥ 8J-OÄ an, die offen operative Chirurgie eigenständig sicher durchzuführen, während dies in der Gruppe 8J-OÄ nur von 39,3 % so eingeschätzt wurde (p 0,001). Keine signifikanten Unterschiede bez. des eigenen Kompetenzniveaus fanden sich bei endourologischen Verfahren (94,1 % vs. 87,9 %) sowie bez. der insgesamt eher niedrig eingeschätzten eigenen Kompetenz in der Laparoskopie (29,4 % vs. 20,6 %) und der robotischen Chirurgie (14,1 % vs. 10,3 %). Trotz der hohen organisatorischen Verantwortung als urologische OberärztInnen hat nur ungefähr ein Drittel der Teilnehmer (34,8 %) eine Weiterbildungsmaßnahme zur Vorbereitung auf Leitungs- und Führungsaufgaben erhalten.Die vorliegende Studie zeigt deutliche Unterschiede bez. der operativen Fertigkeiten in Abhängigkeit von der Dauer der bisherigen OA-Tätigkeit. Außerdem wird eine erhebliche Unzufriedenheit mit der Förderung von Führungsqualitäten und der Vorbereitung auf Führungsaufgaben deutlich. Um qualifiziertes Personal langfristig als urologische OberärztInnen an den Kliniken im Fach Urologie zu binden, erscheint es notwendig, die Bedürfnisse der Berufsgruppe zu berücksichtigen und Defizite durch strategische Förderungen zu beheben.

Die uberwiegende Anzahl von Nierenzellkarzinomen (NCC) wird heutzutage in fruhen Stadien diagnostiziert. Die sog. kleinen Nierentumoren (

To analyze the impact of gender on the clinicopathologic features and survival of patients with surgically treated papillary renal cell carcinoma (papRCC) using a comprehensive international multicenter database.Data of 2325 patients undergoing surgery for unilateral papRCC between 1984 and 2015 in 17 European and North American centers were retrospectively collated. The impact of clinicopathologic features on the likelihood of nephron-sparing surgery (NSS) was evaluated using a multivariable logistic regression model. The influence on cancer-specific mortality (CSM) and other-cause mortality was analyzed by multivariable competing-risk regression models. Finally, subgroup analyses were conducted for organ-confined (n = 2075) and non-organ-confined tumors (n = 250). The median follow-up was 47 months.The study cohort included 1782 (77%) male patients (male-to-female ratio 3.3:1.0). Considering age, symptoms at presentation, performance status, pathologic tumor size, stage, and grade, we observed that there were no significant gender-specific differences. In contrast, female patients underwent NSS significantly less frequently (P .001). On multivariable analysis, the likelihood of NSS was 72% higher in male patients after adjusting for all relevant cofactors (P .001). No significant gender-specific differences in terms of CSM and other-cause mortality were demonstrated, but CSM was 59% lower in female patients in the subgroup of organ-confined tumors (P = .001).No impact of gender on survival was found analyzing this large cohort of patients undergoing surgery for papRCC. However, CSM appears to be lower in female patients with organ-confined disease. In this context, it is interesting that the likelihood of NSS seems to be significantly higher in male patients.

BACKGROUND Outcome of partial nephrectomy (PN) depends on anatomic features of the renal tumor, which can be assessed by nephrometry scores. The aim was to externally validate and refine the Arterial Based Complexity (ABC) score and to compare it to established systems. METHODS Tumors of 300 patients undergoing PN were categorized according to the ABC, RENAL, and PADUA score. Size and tumor invasiveness were combined to form the ABCD score. Correlation analysis and multivariate logistic regression was performed to validate and compare the respective scores as predictors of surgical outcome. RESULTS The ABC score shows significant correlation with ischemia time (IT) (P

A symptomatic pseudoaneurysm (SPA) is a rare but severe complication after partial nephrectomy (PN). Selective trans-arterial embolization (TAE) is the treatment of choice with high success rates. However, the influence of this intervention on postsurgical renal function has not been studied. Between 2005 and 2016 we performed 1047 PNs at our institution. Postsurgical SPA occurred in 40 patients (3.8%). Patients with and without SPA were matched in a 1:2 ratio concerning tumor complexity (RENAL) and pre-operative renal function (CKD stage). Any CKD upstage and a relevant CKD progression (CKD ≥ III) were defined as endpoints. Furthermore, the influence of the amount of contrast agent applied during TAE was assessed. All patients with SPA were treated successfully with TAE. No significant difference could be detected concerning clinical, functional and surgical aspects. Median follow-up time accounted for 12.5 (6.75–27.5) months. Kaplan–Meier analyses detected an increased rate of any CKD upstage (p = 0.066) and relevant CKD progression (p = 0.01) in patients with SPA. Multivariate analysis identified post-operative SPA to be an independent predictor for a relevant CKD progression (HR 4.15, p = 0.01). The amount of contrast agents used did not have an impact on the development of a relevant CKD progression (p = 0.72). Patients treated with TAE after PN show an additional risk for an impairment of renal function over time. Hence, those patients should explicitly be informed about possible consequences and closely monitored by nephrologists.

BACKGROUND/AIM This study investigated the impact of available preoperative imaging on the reliability and predictive accuracy of RENAL and PADUA nephrometry-scoring systems for renal tumors. PATIENTS AND METHODS Five urologists determined RENAL and PADUA scores using preoperative imaging data (computed tomography and magnetic resonance imaging) of 100 patients admitted for partial nephrectomy with the following combinations: T0: transverse planes without excretory phase (EP), TC0: transverse and coronal planes without EP, TC1: transverse and coronal planes with EP. Reference standard was obtained by a uro-radiologist. Ischemia time was used as surrogate for surgical complexity. RESULTS Assignment of EP significantly reduced interobserver-variability among urologists (p

Background To compare the outcomes of robot-assisted (RAPN) and open partial nephrectomy (OPN) for completely endophytic renal tumors. Methods Consecutive patients undergoing OPN or RAPN for entirely endophytic tumors in four high-volume centers between 2008 and 2016 were identified. Endophytic masses were identified based on sectional imaging. Patient characteristics and surgical outcome were compared using Mann-Whitney-U-test and chi-squared-tests. Uni- and multivariate analyses were performed to identify predictors of TRIFECTA achievement and excisional volume loss. Results Out of 1128 patients, 10.9% (64) of RAPN and 13.9% (76) of OPN underwent surgery for entirely endophytic tumors. Operative time was longer for RAPN (169 vs 140 min, P = 0.03) while ischemia time was shorter (13 vs 18 min, P = 0.001). Complication rates were comparable (21% OPN vs 22% RAPN, P = 0.91) and TRIFECTA achievement was not different between the groups (68% OPN vs 75% RAPN, P = 0.39). In multivariate analyses type of surgery was not associated with TRIFECTA achievement or excisional volume loss. Here, only tumor complexity (OR 0.48, P = 0.001) and size (OR 1.01, P = 0.002) were independent predictors. Conclusion For entirely endophytic tumors, both RAPN and OPN offer good TRIFECTA achievement. This encourages the use of NSS even for these highly complex tumors using the surgeon's preferred approach.

Das Nierenzellkarzinom des alten und geriatrischen Patienten erfordert eine Adaptation der klassischen therapeutischen Strategien. Das Management sollte hierbei individuell an Alter und Komorbiditaten angepasst und die Effektivitat und Risiken bzw. Toxizitat aller therapeutischen Optionen uberlegt werden. Ein multidisziplinares Vorgehen von erfahrenen Urologen, Onkologen, Nephrologen, Radiologen, Pathologen, Strahlentherapeuten und ggf. Geriatern, Schmerztherapeuten und Palliativmedizinern ist wichtig fur Diagnose, Assessment und Therapiewahl. Die Empfehlungen sollten mit den einzelnen Patienten und wenn moglich ihren Angehorigen auf die individuellen Bedurfnisse hin diskutiert und eine zu Patientenpraferenzen passende Entscheidung getroffen werden.

Because the prognostic impact of the clinical and pathological features on cancer-specific survival (CSS) and overall survival (OS) in patients with papillary renal cell carcinoma (papRCC) is still controversial, we want to assess the impact of clinicopathological features, including Fuhrman grade and age, on survival in surgically treated papRCC patients in a large multi-institutional series.We established a comprehensive multi-institutional database of surgically treated papRCC patients. Histopathological data collected from 2189 patients with papRCC after radical nephrectomy or nephron-sparing surgery were pooled from 18 centres in Europe and North America. OS and CSS probabilities were estimated using the Kaplan-Meier method. Multivariable competing risks analyses were used to assess the impact of Fuhrman grade (FG1-FG4) and age groups (50 years, 50-75 years,75 years) on cancer-specific mortality (CSM).CSS and OS rates for patients were 89 and 81% at 3 years, 86 and 75% at 5 years and 78 and 41% at 10 years after surgery, respectively. CSM differed significantly between FG 3 (hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.17-8.22; p 0.001) and FG 4 (HR 8.93, 95% CI 4.25-18.79; p 0.001) in comparison to FG 1. CSM was significantly worse in patients aged75 (HR 2.85, 95% CI 2.06-3.95; p 0.001) compared to50 years.FG is a strong prognostic factor for CSS in papRCC patients. In addition, patients older than 75 have worse CSM than patients younger than 50 years. These findings should be considered for clinical decision making.

The aim of this study was to analyze the impact of metabolic syndrome (MetS) on outcome of patients with localized renal cell carcinoma (RCC). A retrospective database was compiled consisting of 646 patients who underwent surgery for localized RCC between 2005 and 2014. A total of 439 patients were eligible for final analysis. For diagnosis of MetS, the WHO criteria of 1998 were used. Median follow-up was 32 months (ranging from 2 to 119). Kaplan-Meier and log-rank analyses were performed to compare patients with and without MetS or its components. Univariate and multivariate logistic regression identified prognostic factors for progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). In our cohort, 9.8% (n = 43) of patients were diagnosed with MetS. There were no differences between patients with and without MetS regarding clinicopathological parameters with the exception of patients’ age (p = 0.002). Kaplan-Meier and log-rank analyses revealed a shorter PFS for patients with MetS (p = 0.018), whereas no differences were found for each of the single components of MetS, namely, diabetes mellitus (DM) (p = 0.332), BMI >30 kg/m2 (p = 0.753), hypertension (p = 0.451), and hypertriglyceridemia (p = 0.891). Logistic regression identified age (HR = 1.92, p = 0.03), tumor stage (HR = 4.37, p

Studies on the prognostic reliability of the Union for International Cancer Control tumor, node, metastasis (TNM) staging system for renal cell carcinoma (RCC) predominantly focus on clear-cell RCC. Therefore, the aim of this study was to investigate whether the oncological prognosis of surgically treated papillary RCC (papRCC) patients is reliably given by the current TNM system, by analyzing the largest database reported to date.Data on 2325 papRCC patients who underwent surgical treatment in 1984- 2015 were collated from 17 international centers (median follow-up 47 months). Tumor stage was adapted to the 7th edition of the TNM system. Multivariable, bootstrap-corrected Cox regression models were applied to assess the independent impact of the TNM system on cancer-specific mortality (CSM) and all-cause mortality (ACM).The median age at diagnosis was 63 years (interquartile range 54-70 years) and 77% of patients were male. Nephron-sparing surgery was performed in 42%, and 82% were with symptom free at diagnosis. In 6.7% (n = 156), organ metastasis (stage M1) was present at the time of surgery. On multivariable analysis, the TNM system and Fuhrman grade had an independent impact on both CSM and ACM, while patient age affected ACM only. The discriminative ability of the pT classification was significant for both endpoints: 5 year CSM rates were 5%, 17%, 36% and 56% for stages pT1, pT2, pT3 and pT4, respectively (each p 0.001). The pT classification contributed significantly to the predictive accuracy of the CSM and ACM models by 6.3% and 2.5%, respectively (each p 0.001).The 2010 TNM staging system can be reliably applied to papRCC patients and allows certain prognostic discrimination.

Background: The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer. Methods: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry. Results: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients. Conclusion: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.

To evaluate the therapeutic methods and algorithms currently used in the treatment of bladder neck contracture (BNC) after radical prostatectomy (RP).Heads of 170 urologic departments in Germany, listed at the German Society of Urology (DGU), were invited to participate in an Internet-based customized survey. The questions consisted of an epidemiologic part (kind of hospital, state of practice) and questions inquiring used surgical techniques with their respective incidence and given algorithms for therapy.Of 170 contacted heads of urologic departments in Germany, 84 responded to the questionnaire (return rate 49.41%). The most common treatment modalities are transurethral resection, cold knife incision, hot knife incision, and dilation in descending order. For those institutions using several treatment modalities, 56 (66.67%) follow a therapeutic algorithm, while 28 (33.33%) follow no set order of treatment. However, among the 56 institutions with a set algorithm, 33 different approaches were identified. Of 84 institutions, 29 (34.52%) perform open reanastomosis in case of recurrent BNC, the remaining 55 (65.48%) do not.Despite several published guidelines on urethral strictures, numerous self-employed treatment algorithms are used to treat BNC. Although treatment results of these algorithms and the underlying treatment modalities cannot be determined with this work, it highlights the necessity for further studies comparing the different surgeries to allow for a more evidence-based approach.

Nephrometry scores are designed for standardized reporting of renal tumors and predicting complications. Multiple scores are available, but there is a lack of systematic comparison.A total of 305 consecutive patients admitted for open partial nephrectomy to 2 urological hospitals were prospectively assessed. Five cases with conversion to radical nephrectomy were excluded from further analysis. RENAL, PADUA, C-index, and NePhRO scores were obtained from preoperative sectional imaging. Additionally, interobserver variance between 2 urologists and a radiologist was analyzed for 50 patients. Linear and ordered logistic regression was used to evaluate the association between scores and surgical parameters. Receiver operating characteristic analysis was employed to assess the predictive value for requirement of ischemia and opening of the collecting system.High interobserver agreement was observed for RENAL (0.92 and 0.80), PADUA (0.81 and 0.85), NePhRO (0.94 and 0.82), and the C-index (0.98 and 0.95). All scores showed a significant association with opening of the collecting system (P .016), requirement of on-clamp excision (P .001), and ischemia time (P .001). Logistic regression identified RENAL, PADUA, and NePhRO score to be an independent predictor for severe complications (P = .016, P = .011, and P = .005). No correlation was found for the C-index (ß = 0.98; P = .779). Predictive effectiveness for opening of the collecting system and for on-clamp excision showed comparable area under the curve values for the 4 scores.All scoring systems represent objective and reproducible measurement tools for renal tumor complexity, that correlate well with surgical outcome. RENAL, PADUA, and NePhRO score are comparable and seem to be superior to the more complex C-index system.

The aim of this study was to evaluate the prognostic relevance of melanoma-associated antigen (MAGE) A9 in renal cell carcinoma (RCC).Immunohistochemical staining for MAGE A9 was evaluated in a tissue microarray containing 587 RCC tumour tissue samples. Nuclear MAGE A9 expression was reviewed using a semiquantitative score. Follow-up has been surveyed since 1990 in a prospectively conducted tumour database. The effect of MAGE A9 expression on cancer-specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. Subgroup analyses were performed for non-metastatic and metastatic disease.Median age in all patients was 63.2 years, 354 patients were male and 233 female, and 108 patients had metastatic disease. Median follow-up was 5.6 years for all patients and 9.0 years for patients still alive (range 0-19.9 years). High nuclear MAGE A9 expression was present in 326 tumour specimens (55.5%). In multivariate analyses high nuclear MAGE A9 expression was associated with poor CSS (p = 0.0027). Furthermore, tumour stage, lymph-node and distant metastasis, Fuhrman grade G3/4, Karnofsky index80% and male gender were associated with poor CSS. In subgroup analyses, results were concordant for patients with non-metastatic disease. In patients with metastatic disease, only Karnofsky index80% was a significant predictor for CSS; MAGE A9 expression could not be shown to be associated with CSS (p = 0.161).High nuclear MAGE A9 expression is independently associated with poor CSS in patients with non-metastatic RCC. The assessment of MAGE A9 expression can provide additional prognostic information and should be used in decision-making regarding adjuvant therapy in patients with non-metastatic disease.

Renal cell carcinomas associated with Xp11.2 translocations have recently been identified as a distinct biological entity. The translocation results in the fusion of the transcription factor TFE3 to one of several different fusion partners including PRCC, PSF, NONO, ASPL or CTLC with consecutive overexpression of the chimeric protein. As the true frequency of these neoplasms as well as the biological properties of TFE3 activation in renal cell carcinomas are largely unknown, we have examined TFE3 expression as well as the underlying genetic alterations in a large, hospital-based series of renal cell carcinomas with long-term follow-up information. Out of a total of 876 tumours, TFE3 translocations were detected in five cases (0.6%). Three additional cases were identified in a second series of cases comprising of renal cell carcinomas developing in patients before the age of 50. However, using immunohistochemistry, 9% of all renal cell carcinomas showed some degree of TFE3 reactivity. Interestingly, these cases were associated with high nuclear grade, greater tumour extent and metastatic disease as well as an unfavourable patient outcome on uni- and multivariate analysis. Fluorescence in situ hybridisation (FISH) revealed TFE3 amplifications as an additional, novel mechanism leading to increased TFE3 expression levels. In conclusion, our data show that Xp11 translocation renal cell carcinomas are uncommon tumours accounting for

CD95 (Fas/APO1) is one of the best known members of the death receptor family which can either mediate apoptosis or activate tumor-promoting pathways. Using a tissue microarray we investigated the association between the expression of CD95 and prognosis in 617 patients with renal cell carcinomas (RCCs). CD95 was expressed in the vast majority of RCCs. High CD95 expression was associated with lymph node metastasis and correlated negatively with disease-specific survival. Multivariate Cox regression analysis confirmed CD95 expression as an independent prognostic factor. In conclusion, high CD95 expression is a negative independent prognostic factor in RCCs which could be used to identify high-risk patients with a poor clinical prognosis.

To investigate prostate-specific antigen density as a predictor for pathologic upstaging in patients initially thought to have unilateral prostate cancer.We analyzed 438 patients with unilateral prostate cancer in prostate biopsy samples that were treated with radical prostatectomy. Bilateral or extracapsular growth in the final surgical specimens was defined as upstaging. Using Kaplan-Meier curves and a multivariate Cox proportional hazard model, we evaluated the oncologic effect of pathologic upstaging on biochemical recurrence-free survival. Prostate-specific antigen density was evaluated as a diagnostic tool to predict upstaging using ROC-curve analysis.Of the patients, 30.8% had bilateral prostate cancer or extracapsular extension in the surgical specimen. Prostate-specific antigen density was a diagnostic predictor for pathologic upstaging in patients initially thought to have unilateral prostate cancer (AUC 0.62, P0.001). Using a lower cutoff value of PSA density0.056 ng/ml/cm3, upstaging could be excluded in patients with a sensitivity of98%.A considerable amount of patients that are initially diagnosed with unilateral prostate cancer on biopsy are underdiagnosed and are upstaged in the radical prostatectomy specimen. In general, AUC of PSA density is too low to use PSA density as diagnostic tool to predict pathologic upstaging in all patients. Nonetheless, PSA density could be used for hemiablative focal therapy decision making using a lower cutoff value of0.056 ng/ml/cm3.

Because of progress in imaging, the incidence of renal tumours, especially small lesions, has been rising over the last years. Therefore, imaging must be done to decide how to proceed further. But which is the most effective modality: computed tomography (CT) or magnetic resonance imaging (MRI)? From the technical point of view, the two alternatives appear to be nearly equal. Multidetector CT remains the reference standard for staging and lesion characterisation, whereas MRI is the method of choice for determining caval extension of a tumour thrombus and infiltration of the renal vein. If an accurate diagnosis cannot be specified, the remaining modality should be used complementarily.

To test the hypothesis that age affects functional results after 80W photoselective vaporization of the prostate (PVP).In 156 patients who were undergoing PVP for benign prostatic hyperplasia (BPH), we assessed the International Prostate Symptom Score (IPSS) and Quality of Life (QoL) score preoperatively and at 12 months. We calculated the association between age and IPSS and QoL results and corrected it for prostate-specific antigen (PSA) value, whose impact on PVP functional results is well accepted.Median patient age was 66 years (interquartile range [IQR] 62-75), median preoperative IPSS 20.5 (IQR 15-25) and QoL 4 (IQR 3-5). At 12 months, the median IPSS percent decrease was 58.8% (range 33%-75%), and the median QoL percent decrease was 66.7% (range 25%-80%). Age was independently associated with both (P0.05). In contrast, after adjustment for age, PSA was not significantly associated with percent IPSS decrease (P = 0.561), and its association with QoL was at the limit of significance (P = 0.05).Age independently and strongly affects IPSS and QoL results at 12 months after 80W PVP.

OBJECTIVES To assess the protein expression of Livin, an apoptosis inhibitor, in renal cell carcinoma (RCC) and to determine its prognostic relevance. PATIENTS AND METHODS Immunohistochemical staining for Livin was performed in tissue microarrays (TMAs), including tumour tissue cores, from patients with RCC who had undergone renal surgery. In 682 TMAs cytoplasmatic staining intensity and nuclear staining quantity were evaluated, and the association of Livin expression with progression-free survival (PFS) and cancer-specific survival (CSS) was analysed with a multivariate Cox regression model. RESULTS Over a median (range) follow-up of 5.2 (0–16.1) years, 204 patients (28%) had died from their disease. The CSS rates at 1 and 5 years for the entire cohort was 88% and 71%. Cytoplasmatic Livin staining was absent in 516 (76%) specimens; staining was positive in 166 (24%) specimens. Weak nuclear Livin staining (≤25%) was present in 571 (84%) specimens, strong nuclear staining (26–100%) in 111 (16%). In multivariate analysis, high (>25%) nuclear Livin expression was a favourable independent predictor of PFS and CSS even after adjusting for tumour stage, Fuhrman grade, age, sex and Karnofsky severity rating. Cytoplasmatic Livin expression did not offer additional prognostic information. CONCLUSION High nuclear Livin expression is a favourable independent predictor of PFS and CSS in patients with RCC.

OBJECTIVE To assess whether under- or overweight at the time of surgery has any effect on the survival of the patients with renal cell carcinoma (RCC), as obesity increases the risk of developing RCC. PATIENTS AND METHODS We prospectively evaluated 780 patients who had nephrectomy for RCC between 1990 and 2005. We used uni- and multivariate Cox proportional hazards models to assess the effect of body mass index (BMI), tumour stage, Fuhrman grade, age, sex, histological type and performance status on cancer-specific survival (CSS). Patients were grouped according to BMI (in kg/m2), as underweight (

Bereits bei Diagnosestellung liegt bei ca. 25–30% aller Patienten mit einem Nierenzellkarzinom eine Metastasierung vor. Bei weiteren 20–30% der Patienten, die sich einer radikalen Nephrektomie mit kompletter Tumorentfernung unterzogen haben, kommt es zu einem Progress. In diesem Ubersichtsartikel wird auf die aktuellen therapeutischen Optionen beim metastasierten Nierenzellkarzinom eingegangen. Dazu zahlen im Einzelnen die operativen Therapieoptionen wie zytoreduktive Tumornephrektomie oder Metastasenchirurgie aber auch die Embolisation, medikamentose Therapieansatze (Chemotherapie, Immuntherapie und „targeted therapy“) sowie die supportive Schmerztherapie.

OBJECTIVES To evaluate the thoraco-abdominal approach for resection of retroperitoneal tumours, as this approach is rarely used because, although exposure is excellent, morbidity is presumed to be increased. PATIENTS AND METHODS From October 2003 to September 2005, 21 patients (six female, 15 male), aged 14-76 years, underwent resection of very large and/or T4 retroperitoneal tumours through a thoraco-abdominal approach. RESULTS In 16 (76%) patients tumour resection was complete. There were no significant complications during surgery. After surgery, there were complications in six patients (29%), in four of whom there was no long-term impairment. One patient died at 75 days after surgery from a complicated retroperitoneal haematoma. The mean (range) estimated blood loss was 2883 (50-20 000) mL, the intensive-care unit stay was 3.85 (0-30) days and the intermediate-care unit stay 2.6 (0-9) days. With a mean follow-up of 9.6 (1-19) months, 15 patients (72%) are recurrence-free, two (10%) have progressive disease, and four (19%) have died from malignancy. CONCLUSIONS The thoraco-abdominal approach permits excellent exposure of the retroperitoneum for large and/or T4 tumours, allowing radical surgery in cases considered otherwise inoperable. Additional advantages are the possibilities of early vascular control and easy surgical extension of the procedure. These facts, combined with the reasonable morbidity found in our series, support the integration of the thoraco-abdominal approach in the regular options for urological surgery.

Objective: The aim of this prospective study is to determine the diagnostic accuracy of multidetector-row computed tomography (CT) compared to histopathologic findings in tumor staging of renal cell carcinoma, with the focus on tumor stage, vein and artery infiltration, and infiltration of the renal pelvis. Materials and Methods: In a prospective study, a total of 76 consecutive patients with suspected renal cell carcinoma were preoperatively assessed for tumor staging using multidetector-row CT. Triphasic CT imaging (i.e., noncontrast, arterial, and parenchymal phase) was performed using multidetector-row CT with reconstructed slice thicknesses of 2 and 5 mm. Two blinded readers evaluated the CT scans independently; the results were then correlated with the histopathologic results. Results: A total of 56 renal cell carcinomas were proven on histopathology. Readers 1 and 2 reached a sensitivity of 1.0 and 1.0 and a specificity of 0.41 and 0.42 for arterial infiltration, a sensitivity of 1.0 and 0.86 and a specificity of 0.58 and 0.5 for venous infiltration, and a sensitivity of 0.75 and 1.0 and a specificity of 0.5 and 0.44 for infiltration of the renal pelvis. The correlation between both readers was 0.7 for all modalities. Conclusions: The multiplanar reconstruction capability of multidetector-row CT allowed good sensitivity in predicting arterial infiltration. The lowest specificity was reached in excluding infiltration of the renal pelvis. Despite its high temporal and spatial resolution, the capacity of multidetector CT to predict intrarenal infiltrations is still limited.

OBJECTIVE To evaluate the role of neuropeptide Y in the detrusor of patients with neurogenic detrusor overactivity (NDO), as it has an important role in the neural regulation of the lower urinary tract by exerting differential effects on the release of cholinergic and adrenergic transmitters via autoinhibition and heterosynaptic interactions MATERIALS AND METHODS Detrusor biopsies were obtained from 38 patients; 31 had video-urodynamically verified NDO, caused by meningomyelocele in 17 or spinal cord injury in 14. Seven had stress urinary incontinence (SUI) and this group served as a control. All specimens were fixed, paraffin wax-embedded, sectioned and stained with a monoclonal antibody against neuropeptide Y and a general nerve marker protein-gene-product 9.5 (PGP 9.5). The number of PGP 9.5- and neuropeptide Y-containing nerves was quantified by a standardized evaluation using image-analysis software. RESULTS The median (range) number of neuropeptide Y-containing nerves in the neurogenic detrusor, at 0.273 (0.126–0.639) per muscle cell nucleus (MCN), was significantly lower (P = 0.014) than that in patients with SUI, at 0.383 (0.267–0.728). In the neurogenic detrusor the number of PGP 9.5-positive nerves, at 0.278 (0.054–0.641)/MCN was also lower (P = 0.111) than in patients with SUI, at 0.368 (0.258–0.497). The ratio of neuropeptide Y to PGP 9.5 counts per biopsy did not differ between the groups (P = 0.628). CONCLUSIONS The number of PGP 9.5-positive nerves was not significantly and the number of neuropeptide Y-containing nerves was significantly reduced in patients with NDO. This may have been caused by transynaptic nerve degeneration of the detrusor, as described by in patients with spinal cord injury. As neuropeptide Y inhibits the contractile response of the detrusor the reduction of neuropeptide Y-containing nerves may play a role in the development and persistence of DO.

OBJECTIVE To immunohistochemically identify the protein composition of adherens junctions, which couple smooth muscle cells mechanically, and to confirm their decrease in different bladder dysfunctions, as studies in geriatric bladder dysfunction show fewer such junctions in patients with detrusor overactivity (DO) and bladder outlet obstruction (BOO). MATERIAL AND METHODS Detrusor biopsies were obtained from video-urodynamically evaluated patients with neurogenic DO (NDO, 31 patients), BOO (six patients) and from six patients with stress urinary incontinence (SUI) with stable, unobstructed detrusors (serving as controls). Specimens were fixed, paraffin-embedded, sectioned, stained with a polyclonal pan-cadherin antibody, monoclonal α-, β- and γ-catenin antibodies, and a monoclonal integrin-β1 antibody. All antibodies were known to react with proteins of adherens junctions. Two examiners unaware of sample origin evaluated the sections qualitatively and using a semiquantitative scale. The results were correlated with the patient groups. RESULTS Specific immunohistochemical staining of pan-cadherin, α-, β- and γ-catenin could not be detected in any detrusor smooth muscle compartment, but was present in the urothelium. There was integrin-β1 reactivity in the basement membranes of bladder smooth muscle cells in 38 of 43 detrusor biopsies. There were no differences among the three groups. CONCLUSION The known proteins of cell-cell adherens junctions are not part of the cell-cell junctions of detrusor smooth muscle. The specific staining of integrin-β1 indicates either the presence of cell-matrix junctions or of cell-cell junctions within the human detrusor. Further studies are needed to identify the complete protein composition of adherens junctions within smooth muscle cells.

Purpose: To report our experience with temsirolimus in 2nd-, 3rd- and 4th-line therapy for patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: In our prospectively maintained tumor registry, we identified 6 mRCC patients with temsirolimus in >1st-line systemic therapy. Patients were followed by weekly clinical and laboratory examination during admission of temsirolimus. Re-staging with chest CT and abdominal MRI was performed every 3 months. Results: We observed excellent response rates. Progression-free survival (PFS) ranged from 6 to 40 months with a median of 15 months. Treatment was generally well tolerated. However, pneumonitis was observed in 4 of 6 patients. Drug-related pneumonitis led to severe dyspnea, with the result that treatment with temsirolimus had to be interrupted for a short period of time in 2 patients and discontinued in 1 patient. Conclusions: Temsirolimus proved to be a very good treatment option in 2nd- to 4th-line therapy with excellent response rates and manageable side effects. The incidence of pneumonitis must not be underestimated.

Introduction: Hydronephrosis and BMI are analyzed together with established factors such as TNM stage and surgical margins in a multivariate modality to investigate their status as independent prognostic factors for bladder cancer-specific survival in patients undergoing radical cystectomy. Patients and Methods: We studied a prospective cohort of 328 patients who underwent radical cystectomy for bladder cancer at our institution. Statistical analyses were performed using the Kaplan-Meier method, Kendall-tau rank correlation and multivariate Cox proportional hazard model. Results: Hydronephrosis was positively correlated with advanced tumor stage, positive lymph node involvement and positive surgical margins. Adjusted for all other investigated parameters, BMI and hydronephrosis did not affect cancer-specific survival. In multivariate analysis only non-organ-confined disease (HR: 1.40, 95% CI: 1.04–1.87, p = 0.024), positive lymph node stage (HR 1.71: 95% CI: 1.12–2.61, p = 0.013) and positive surgical margins (HR 3.00, 95% CI: 1.74–5.15, p < 0.001) were prognostic factors. Conclusions: Hydronephrosis at the time of radical cystectomy is significantly correlated with the presence of more advanced bladder cancer and positive surgical margins. However, the long-established parameters pT stage, pN stage and surgical margins predominantly influence cancer-specific survival for patients undergoing radical cystectomy irrespective of hydronephrosis and BMI status.