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Supplementary figure S8. Progression-free survival curve in patients with EAU high risk tumors of a combination of FGFR3 and GATA2 status. Blue: good status (hypomethylated GATA2 and mutated FGFR3), green; moderate status (either hypermethylated GATA2 and mutated FGFR3 or hypomethylated GATA2 and wild type FGFR3) or red: poor status (hypermethylated GATA2 and wild type FGFR3) compared to a progression free survival curse in all EAU high risk patients. Progressive disease is defined as progression to stage T2 or higher stage disease.

Supplementary Table S2. Cut-offs for dichotomization of the methylation marker results were chosen based on the desired sensitivity-specificity trade-off for progression to MIBC as visualized by the receiver-operating characteristic curve (ROC curve); the point on the curve closest to the upper left corner.

Purpose: The European Association of Urology (EAU) guidelines for non–muscle-invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathologic parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC.Experimental Design: We prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3, and ZIC4 methylation and FGFR3, TERT, PIK3CA, and RAS mutation status. Cox regression analyses identified markers that were significantly associated with progression to muscle-invasive disease. The progression incidence rate (PIR = rate of progression per 100 patient-years) was calculated for subgroups.Results: In our cohort, 276 patients had a low, 273 an intermediate, and 555 a high risk of tumor progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%) progressed to muscle-invasive disease. The limited number of progressors in this large cohort compared with older studies is likely due to improved treatment in the past two decades. Overall, wild-type FGFR3 and methylation of GATA2 and TBX3 were significantly associated with progression (HR = 0.34, 2.53, and 2.64, respectively). The PIR for EAU high-risk patients was 4.25. On the basis of FGFR3 mutation status and methylation of GATA2, this cohort could be reclassified into a good class (PIR = 0.86, 26.2% of patients), a moderate class (PIR = 4.32, 49.7%), and a poor class (PIR = 7.66, 24.0%).Conclusions: We conclude that the addition of selected biomarkers to the EAU risk stratification increases its accuracy and identifies a subset of NMIBC patients with a very high risk of progression. Clin Cancer Res; 24(7); 1586–93. ©2018 AACR.

Background: Cognitive impairment is poorly addressed in G8 screening. Aim of the presents study was to evaluate the additional value of Mini-Cog© in urogeriatric patients concurrently screened by G8 scores. Methods: 74 consecutive urogeriatric patients at the age of 75 and above were evaluated. All underwent G8 and Mini-Cog© screening. Patients with a G8 score above 14 were considered geriatric “healthy or fit”. A Mini-Cog© of four to five points was considered inconspicuous in screening for cognitive impairment. The additional information of a Mini-Cog© screening during G8 screening was evaluated by looking at G8 “fit and healthy” patients who had conspicuous Mini-Cog© tests and vice versa. Additionally, the results of the neuropsychological subitem “E” of the G8 score were compared with the results of Mini-Cog© screening. Results: Mean age of the patients was 83 y (min. 75 – max. 102). 61 of the patients were males and 13 females. 29 of the patients had a normal G8 score and were considered “healthy or fit” and 45 not. 43 of the patients had an inconspicuous and 31 a conspicuous Mini-Cog© of less than four points. The majority of G8 “healthy or fit” patients (n=24/29) had an inconspicuous Mini-Cog© test. However, of them 5 patients had a Mini-Cog© of less than four points suspicious for cognitive disorders. Furthermore, of the 43 patients with a normal G8 sub score in item “E” of two points, 6 patients had a conspicuous Mini-Cog© of less than four points. Conclusion: As shown by the present study, the Mini-Cog© helpfully extends the G8 screening with regard to the detection of cognitive functional impairments that are not detected by the G8 screening alone. It can be easily added to G8 screening.

Background: The genomic landscape of cancer is complex and includes mutations and copy number alterations (CNAs) that affect several cancer related pathways and drive tumor evolution. Non-muscle-invasive bladder cancers (NMIBC) are largely orphan for integrative genomic studies. Large studies are needed to delineate the genomic complexity and heterogeneity of NMIBC. Methods: A total of 438 patients with NMIBC were analyzed, 296 of which were part of the UROMOL cohort (PMID: 27321955). The median follow-up was 5 years. The progression rate was 13% (n= 56). Whole exome sequencing (WES) was performed on DNA from tumor (~150x) and matched germline samples to call somatic mutations. Additionally, shallow whole genome sequencing (sWGS; ~2x) was performed on DNA from 362 of the tumors to quantify CNAs. RNA-sequencing was available for 414 of the samples, and tumors were classified according to the UROMOL2021 transcriptomic classes. We identified significantly mutated genes by mutsigCV and significantly amplified or deleted regions by GISTIC2. Results: The median tumor mutation burden (TMB) was 3.7/Mb. TMB was not associated with progression (p=0.28). A total of 61 genes were significantly mutated in the cohort, the most frequent being FGFR3 (61%), KDM6A (44%) and KMT2D (38%). Mutations in EP300 and RHOB were significantly associated with an increased risk of progression after adjusting for grade and stage (p=0.040 and 0.044, respectively). Several mutations showed a strong transcriptomic class dependent occurrence: mutations in RB1, TP53, ERCC2 and ERBB2 were enriched in the aggressive class 2a, FGFR3 and STAG2 in class 1 and class 3, and KMT2C and KMT2D in class 3. Genome doubling was identified in 15% of the tumors. These tumors were enriched in the aggressive classes 2a and 2b and were associated with increased risk of progression (p=0.0049). In addition, we observed several significantly altered genomic regions, the most significant being deletions in 9p21.3 (CDKN2A & CDKN2B, 64%), 2q37.1 (GIGYF2 & EIF4E2, 28%) and amplification in 11q13.3 (CCND1, 9%). Class 2a tumors were enriched for genomic alterations in most of the significant regions. 9p21.3 was the only region with frequent homozygous losses (22%). High-level gains were prognostic of progression, independently of ploidy, stage and grade, for several regions, including 4p16.3 (FGFR3, p=0.00013), 17q23.2(TBX2, p=0.0004) and 8p11.23(ZNF703, p=0.011). In addition, we observed an enrichment of uniparental disomy in 4p16.3 (FGFR3, 8%). Conclusion: Here we investigated the landscape of DNA alterations in NMIBC in a large patient cohort of NMIBC samples with paired transcriptomic data and detailed clinical follow-up. We identified several novel genomic alterations; specifically, we showed that 15% of the tumors had genome doublings, and we identified a complex underlying copy number landscape of the region containing FGFR3. Citation Format: Frederik Prip, Philippe Lamy, Iver Nordentoft, Sia Viborg Lindskrog, Trine Strandgaard, Karin Birkenkamp-Demtröder, Gregers G. Hermann, Astrid C. Petersen, Veronika Bahlinger, Marc-Oliver Grimm, Marcus Horstmann, Karin Mogensen, Roman Nawroth, Ulrika Segersten, Danijel Sikic, Kim E. M van Kessel, Tobias Maurer, Tatjana Simic, Arndt Hartmann, Ellen C. C. Zwarthoff, Per-Uno Malmström, Torben Steiniche, Jørgen Bjerggaard Jensen, Núria Malats, Francisco X. Real, Lars Dyrskjøt. Comprehensive genomic characterization of early-stage bladder cancer from 438 patients by whole genome- and exome sequencing. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6075.

ZusammenfassungDer zirkuläre Prolaps der inneren Urethralschleimhaut ist ein seltener Befund. Häufiger treten Harnröhrenkarunkel auf, die sich meist aus der dorsalen externen Lippe des Meatus entwickeln. Wir berichten über die chirurgische Resektionstechnik mit Quadrantenresektion bei einer postmenopausalen Patientin mit einem ausgeprägten Urethralprolaps und chronischer Obstipation. Durch die Operation wurde eine schnelle Schmerzfreiheit und Verbesserung der Miktion erzielt. Die Kontinenz blieb erhalten. Alternative Therapien zur Resektion sind konservative Therapieversuche mit Sitzbädern und oestrogenhaltigen Salben, manuelle Reposition in Narkose und die zirkuläre Ligatur des Prolapses um einen liegendem transurethralen Blasenkatheter.

ZusammenfassungDer G8-Fragebogen ist ein von der SIOG und EAU empfohlenes geriatrisches Screening-Tool, das zum Zeit- und Ressourcenschonen einem kompletten geriatrischen Assessment („comprehensive geriatric assessment“, CGA) vorgeschaltet werden kann. Die Anwendung des Fragebogens hat sich in unserem klinischen Alltag bewährt, da die 8 Items schnell und problemlos in 4 – 5 Minuten im Stil einer Checkliste auch von nicht geriatrisch geschultem Personal bearbeitet werden können. Mittlerweile ist der G8-Fragebogen in der geriatrischen Onkologie ein etabliertes Screening-Tool. Mehrfach wurde in Studien bewiesen, dass er einen unabhängigen Vorhersagewert in Bezug auf das Gesamtüberleben von Patienten hat. Kritische Aspekte bei der Anwendung bleiben seine relativ geringe Testspezifität (60 %), sein Fokus auf Ernährungsaspekte und mögliche Interobserverdifferenzen. Diese Aspekte sollten vom Anwender gekannt und beachtet werden.

The topic of routine medical care data and healthcare science has gained in relevance and provides an important basis for both healthcare policymakers and those providing care. Access to relevant data and the ability to analyze these is highly competitive as it yields the most compelling arguments and strong facts in any discourse on the ultimately limited resources of the entire healthcare sector. All randomized clinical trials and prospective data collections harbor the inherent similarity that they contain data within a predefined frame of data elements in order to control for any confounding factors. In addition, analyses using retrospective data collections use a predefined evaluation matrix and filter the existing data according to these established data elements. However, an unfiltered and un(pre)specified view to all data would be ideal. An approximation to this goal as part of this project could be the unfiltered collection of as much data as possible and their collection in a data pool, which then could be processed, in a constantly improving analyses algorithm. The automated self-extraction of data from the private-practice information technology (IT) system to UROscience will create a data pool which could be used to answer many different questions related to the reality of healthcare. The preliminary analyses presented here demonstrate that, on basis of the existing data, this versatile sample is available to provide insight into the treatment reality of urologic outpatient care.Auch (berufs)politisch hat das Thema Versorgung und Versorgungsforschung an Relevanz gewonnen und stellt für die Gesundheitspolitik und die an der Versorgung Beteiligten eine wichtige Basis dar. Der Zugang zu relevanten Daten und die Möglichkeiten zur Analyse sind daher umkämpfter denn je, liefern sie doch die besten Argumente und Fakten in jedem Diskurs um letztlich begrenzte Ressourcen des gesamten Gesundheitssektors. Allen randomisierten klinischen Studien und prospektiven Datensammlungen ist gemein, dass sie einen festen vordefinierten Rahmen der zu erfassenden verschiedenen Datenpunkte zugrunde gelegt haben, um störende Einflussfaktoren möglichst zu kontrollieren. Auch Analysen aus retrospektiven Datensammlungen benutzen eine vordefinierte Auswertematrix und filtern die vorhandenen Daten auf diese festgelegten Datenpunkte. Ein ungefilterter Blick auf alle Daten wäre aber der Idealzustand. Näherungsweise sollten in diesem Projekt so viele Daten wir möglich „ungefiltert“ erfasst werden und in einem Datenpool gesammelt werden, die dann durch sich ständig verbessernde Analysealgorithmen aufgearbeitet werden können. Über die automatisierte Extraktion von Daten aus dem Arzt‑/Praxisinformationssystem (AIS) in UROscience wird ein Datenpool entstehen, der für viele Fragestellungen zur Versorgungsrealität genutzt werden kann. Die hier vorgestellte erste Analyse zeigt, dass auf Basis der bereits vorhandenen Daten eine vielseitig einsetzbare Stichprobe für die Darstellung des Versorgungsalltags aus der urologischen Praxis zur Verfügung steht.

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials., Multiple molecular profiling methods are required to study urothelial non-muscle-invasive bladder cancer (NMIBC) due to its heterogeneity. Here the authors integrate multi-omics data of 834 NMIBC patients, identifying a molecular subgroup associated with multiple alterations and worse outcomes.

Urethral prolapses in humans are rare. Urethral caruncula are more frequent. Caruncula originate from the dorsal external layer of the urethral meatus. We report on the surgical approach used for the resection of a huge urethral prolapse in a postmenopausal woman with chronic constipation using the four-quadrants resection technique. After the procedure, the patient was quickly relieved from pain and micturition was improved. The patient was fully continent. Alternative treatments to surgical resection include conservative approaches with sitz baths and oestrogen cremes, manual reduction under general anaesthesia and ligation of the prolapse around a transurethral bladder catheter.Der zirkuläre Prolaps der inneren Urethralschleimhaut ist ein seltener Befund. Häufiger treten Harnröhrenkarunkel auf, die sich meist aus der dorsalen externen Lippe des Meatus entwickeln. Wir berichten über die chirurgische Resektionstechnik mit Quadrantenresektion bei einer postmenopausalen Patientin mit einem ausgeprägten Urethralprolaps und chronischer Obstipation. Durch die Operation wurde eine schnelle Schmerzfreiheit und Verbesserung der Miktion erzielt. Die Kontinenz blieb erhalten. Alternative Therapien zur Resektion sind konservative Therapieversuche mit Sitzbädern und oestrogenhaltigen Salben, manuelle Reposition in Narkose und die zirkuläre Ligatur des Prolapses um einen liegendem transurethralen Blasenkatheter.

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identified four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provided independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations were significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration was associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirmed the higher infiltration of class 2b tumors and demonstrated an association between higher immune cell infiltration and lower recurrence rates. Finally, a single-sample classification tool was built and the independent prognostic value of the transcriptomic classes was documented in 1306 validation samples. The classifier provides a framework for novel biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.

Zusammenfassung Einleitung Das Urothelkarzinom der Harnblase ist ein Tumor des höheren Lebensalters. Mit dem demografischen Wandel nimmt die Zahl sehr alter Patienten (> 80 J), die sich einer TUR-B unterziehen müssen, zu. Material und Methoden In einer retrospektiven Analyse wurden die perioperativen Komplikationen von 89 Patienten > 80 Jahren, bei denen zwischen 2013 und 2016 an unserer Klinik eine TUR-B durchgeführt worden war, nach der Clavien Dindo-Klassifikation evaluiert. Ergebnisse Das mittlere Patientenalter lag bei 87 J (82 – 94). 81 (91 %) Patienten waren unter oraler Antikoagulation (32 × ASS, 24 × NOAK, 25 × Marcumar). Histologisch wurde bei 25/89 (28 %) Patienten kein Tumor detektiert, bei 28/89 (31 %) ein pTa, bei 22/89 (25 %) ein pT1 und bei 14/89 (16 %) ein T2-Tumor oder höher detektiert. Insgesamt traten nach der Clavien Dindo-Klassifikation bei 36/89 (40 %) Patienten Komplikationen auf. Bei 21/89 (23 %) Patienten kam es zur prolongierten spülpflichtigen Makrohämaturie mit einer erneuten TUR-B bei 5/89 Patienten (6 %). 14 Patienten wurden transfundiert, 6 davon präoperativ. Nach Clavien Dindo wurden die Komplikationen bei 4/89 (4 %) Patienten als max. I, bei 21/89 (24 %) als max. II, bei 5/89 (6 %) Pat. als max. IIIb und bei 3/89 (3 %) als max. IVa gewertet. Drei (3 %) Patienten verstarben postoperativ (Clavien V): Ein Patient infolge einer Aspirationspneumonie (86 J, ASA IV), einer infolge einer Lungenembolie (90 J, ASA IV) und einer infolge eines Multiorganversagens (84, ASA III). In multivariaten Analysen bestätigte sich ein Tumorstadium > T2 als signifikanter Prädikator für das Auftreten von postoperativen Komplikationen (Odds Ratio von 9,54 (95 %CI 1,14 – 84,67; p = 0,032). Für die oralen Antikoagulantien ergab sich eine Odds Ratio von 4,10 (95 %CI, 41,00 – 1,23; p = 0,050). Schlussfolgerung Insgesamt zeigen die Daten, dass die TUR-B bei Patienten > 80 J abhängig von vorliegenden Risikofaktoren mit einer erhöhten Komplikationsrate behaftet durchführbar ist. Prolongierte Makrohämaturie und die hohe Transfusionsrate sind v. a. auf den hohen Anteil oral antikoagulierter Patienten zurückzuführen.

Cytokeratin 20 (CK20) and insulin-like growth factor 2 (IGF2) were previously proposed to be elevated in clinical samples from patients with bladder cancer (BCa). A two cohort design validation study was used to assess the relevance for BCa detection by transcript quantitation of both markers in urine samples. Their diagnostic value was assessed in comparison with voided urine cytology (VUC). RNA isolation was carried out using cellular sediments of urine samples from 196/103 histologically positive BCa patients, as well as 97/50 control subjects for the test (TC) and validation cohort (VC), respectively. Urinary transcript levels of CK20 and IGF2 were determined by qPCR. Relative transcript levels were significantly elevated 3.4/11-fold for CK20 and 188/64-fold for IGF2 (p

The G8 questionnaire is a geriatric screening tool recommended by the SIOG and the EAU. To save time and resources, it can precede a comprehensive geriatric assessment (CGA) in a two-step evaluation. Based on our experience, this 8-item questionnaire is easy and fast to perform (4 - 5 minutes), even by medical staff untrained in geriatrics. The G8 questionnaire has become an established screening tool also in geriatric oncology. It has been shown in several studies that it provides an independent prognostic indicator for the overall survival of cancer patients. However, some critical aspects remain: its low specificity (60 %), its focus on nutritional aspects, and possible interobserver differences. These aspects should be known and taken into account by clinicians.Der G8-Fragebogen ist ein von der SIOG und EAU empfohlenes geriatrisches Screening-Tool, das zum Zeit- und Ressourcenschonen einem kompletten geriatrischen Assessment („comprehensive geriatric assessment“, CGA) vorgeschaltet werden kann. Die Anwendung des Fragebogens hat sich in unserem klinischen Alltag bewährt, da die 8 Items schnell und problemlos in 4 – 5 Minuten im Stil einer Checkliste auch von nicht geriatrisch geschultem Personal bearbeitet werden können. Mittlerweile ist der G8-Fragebogen in der geriatrischen Onkologie ein etabliertes Screening-Tool. Mehrfach wurde in Studien bewiesen, dass er einen unabhängigen Vorhersagewert in Bezug auf das Gesamtüberleben von Patienten hat. Kritische Aspekte bei der Anwendung bleiben seine relativ geringe Testspezifität (60 %), sein Fokus auf Ernährungsaspekte und mögliche Interobserverdifferenzen. Diese Aspekte sollten vom Anwender gekannt und beachtet werden.

Routine second transurethral resection (TUR) for non-muscle-invasive bladder cancer (NMIBC) is common practice in Germany. Applicability of European Organization for Research and Treatment of Cancer (EORTC) and Spanish Urological Club for Oncological Treatment (CUETO) models in NMIBC patients is still controversial. Aim of the study was to assess the performance of EORTC and CUETO predictive models in NMIBC patients treated with second TUR. 479 NMIBC patients with routine second TUR were analyzed retrospectively between 2003 and 2011, and investigated with clinical and pathological variables in regard to tumor recurrence and progression. Furthermore, recurrencefree survival (RFS) and progression-free survival (PFS) were evaluated according to EORTC and CUETO, and the discrimination of the models assessed. With a median follow-up of 60 months, prior recurrence rate, grade, and second TUR pathology were independent prognostic factors for the risk of disease recurrence and progression. The concordance index of the EORTC and the CUETO model was 0.563 and 0.516 for recurrence and 0.681 and 0.702 for progression, respectively. The positive pathology after second TUR was significantly associated with risk of disease recurrence and progression. EORTC and CUETO risk models estimated progression better than recurrence, especially with higherscore groups. Improved predictive tools should be developed for optimal treatment selection.

Urothelial carcinoma of the urinary bladder is a tumour of advanced age. The demographic change increases the number of very old patients ( 80 years) subjected to TUR-B. In a retrospective analysis, perioperative complications in 89 patients ( 80 years), who underwent a transurethral resection of the bladder between 2013 and 2016 in our department, were recorded and evaluated using the Clavien-Dindo grading system. Mean patient age was 87 years (82 - 94). 81 patients (91 %) were treated with oral anticoagulants (32 × ASA, 24 × NOACs, 25 × Marcumar). A histological examination revealed no tumour in 25/89 (28 %) patients, pTa in 28/89 (31 %), pT1 in 22/89 (25 %) and pT2 or higher in 14/89 patients (16 %), respectively. A total of 36/89 (40 %) patients experienced complications according to the Clavien-Dindo classification. 21/89 (23 %) of patients had a prolonged bladder irrigation due to macrohaematuria, 5/89 (6 %) needed surgical reintervention. 14 (12.4 %) patients needed a blood transfusion, 6 (5.3 %) of them preoperatively. According to the Clavien-Dindo classification, 4/89 (4 %) patients were graded as I, 21/89 (24 %) as II, 5/89 (6 %) as IIb and 3/89 (3 %) as IVa, respectively. Three patients (3 %) died postoperatively (Clavien-Dindo V). One of them died as a result of aspiration pneumonia (86 y, ASA IV), one as a result of pulmonary embolism (90 y, ASA IV) and one as a result of multiorgan failure (84 y, ASA III). In multivariate analyses, a tumour stage T2 was confirmed as a significant predictor of the occurrence of postoperative complications (odds ratio of 9.541 (95 % CI 1.14 - 84.67 p = 0.032). For oral anticoagulants the odds ratio was 4.10 (95 % CI, 41.00 - 1.23, p = 0.050).Overall, the data show that a TUR-B is feasible in patients 80 years with an increased complication rate in comparison to younger patients. Prolonged macrohaematuria and a high transfusion rate are attributable to the high percentage of orally anticoagulated patients. Das Urothelkarzinom der Harnblase ist ein Tumor des höheren Lebensalters. Mit dem demografischen Wandel nimmt die Zahl sehr alter Patienten ( 80 J), die sich einer TUR-B unterziehen müssen, zu. In einer retrospektiven Analyse wurden die perioperativen Komplikationen von 89 Patienten 80 Jahren, bei denen zwischen 2013 und 2016 an unserer Klinik eine TUR-B durchgeführt worden war, nach der Clavien Dindo-Klassifikation evaluiert. Das mittlere Patientenalter lag bei 87 J (82 – 94). 81 (91 %) Patienten waren unter oraler Antikoagulation (32 × ASS, 24 × NOAK, 25 × Marcumar). Histologisch wurde bei 25/89 (28 %) Patienten kein Tumor detektiert, bei 28/89 (31 %) ein pTa, bei 22/89 (25 %) ein pT1 und bei 14/89 (16 %) ein T2-Tumor oder höher detektiert. Insgesamt traten nach der Clavien Dindo-Klassifikation bei 36/89 (40 %) Patienten Komplikationen auf. Bei 21/89 (23 %) Patienten kam es zur prolongierten spülpflichtigen Makrohämaturie mit einer erneuten TUR-B bei 5/89 Patienten (6 %). 14 Patienten wurden transfundiert, 6 davon präoperativ. Nach Clavien Dindo wurden die Komplikationen bei 4/89 (4 %) Patienten als max. I, bei 21/89 (24 %) als max. II, bei 5/89 (6 %) Pat. als max. IIIb und bei 3/89 (3 %) als max. IVa gewertet. Drei (3 %) Patienten verstarben postoperativ (Clavien V): Ein Patient infolge einer Aspirationspneumonie (86 J, ASA IV), einer infolge einer Lungenembolie (90 J, ASA IV) und einer infolge eines Multiorganversagens (84, ASA III). In multivariaten Analysen bestätigte sich ein Tumorstadium T2 als signifikanter Prädikator für das Auftreten von postoperativen Komplikationen (Odds Ratio von 9,54 (95 %CI 1,14 – 84,67; p = 0,032). Für die oralen Antikoagulantien ergab sich eine Odds Ratio von 4,10 (95 %CI, 41,00 – 1,23; p = 0,050). Insgesamt zeigen die Daten, dass die TUR-B bei Patienten 80 J abhängig von vorliegenden Risikofaktoren mit einer erhöhten Komplikationsrate behaftet durchführbar ist. Prolongierte Makrohämaturie und die hohe Transfusionsrate sind v. a. auf den hohen Anteil oral antikoagulierter Patienten zurückzuführen.

BACKGROUND: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed.OBJECTIVE: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study.DESIGN, SETTING, AND PARTICIPANTS: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions.RESULTS AND LIMITATIONS: The progression score was significantly (pCONCLUSIONS: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens.PATIENT SUMMARY: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.

Hematuria is the main symptom of many urological and nephrological diseases. In the differential diagnostics a distinction is made between painful and pain-free and between macrohematuria which is visible to the naked eye and microhematuria which is not visible. The reasons for hematuria are basically renal (glomerular) and non-renal (non-glomerular) causes. In order not to overlook early symptoms of malignant and relevant benign diseases and also to avoid excessive diagnostic tests, a differentiated approach is necessary.

To evaluate FISH analysis of washing urine from the upper urinary tract (UUT) in comparison with cytology (Cyt) for the detection of urothelial cancers. In 82 patients with symptoms or abnormalities of the UUT sampling of washing urine for FISH and Cyt and a stepwise diagnostic work-up (e.g. retrograde ureteropyelography, ureterorenoscopy and endoscopic biopsy) were performed. In case of endoscopically and/or histologically proven malignancy patients either underwent nephroureterectomy, partial ureterectomy or local treatment. Sensitivity and specificity for FISH and Cyt as well as its combination were determined. Urothelial cancer of the UUT was detected in 20 patients. Eleven patients underwent nephroureterectomy, six partial ureterectomy and three endoscopic tumour treatment. This revealed nine pTa, three pT1 and seven muscle-invasive tumours. Twelve tumours were classified as low and seven as high-grade tumours. In one patient with a macroscopic unequivocal finding of tumour, endoscopic laser ablation without histologic confirmation was performed. FISH was evaluable in 76 patients and detected 16 tumours with a sensitivity and specificity of 84.2 and 91.1 %, respectively. Cyt was performed in 79 and was evaluable in 78 patients. It detected ten tumours with a sensitivity and specificity of 52.6 and 91.4 %, respectively. Cyt and FISH together detected 19 tumours with (sensitivity 100 % and specificity 83.6 %). FISH was more sensitive than and equally specific to Cyt in the detection of urothelial cancers of the UUT. Both markers in combination revealed the best sensitivity, making it a possible approach in future settings.

Upper tract urothelial carcinomas in the proximal ureter are an uncommon disease. We present a case in which it was firstly detected by fluorescence in situ hybridization and not by endoscopy and radiologic imaging. Consequently, a radical nephroureterectomy with excision of the bladder cuff was performed as the gold standard treatment.

Objective: To evaluate Kisspeptin-10 (Kiss-10) in patients with small renal tumours (SRTs) and controls. Material and Methods: Kiss-10 was measured in preoperative plasma samples in a cohort of 143 patients with unilateral renal tumours smaller than or equal to 4 cm and 40 age-matched controls by a competitive ELISA test kit. The cohort of patients included 56 patients with clear cell renal cell carcinoma (ccRCC), 43 with papillary RCC (pRCC), 12 with chromophobe RCC (chRCC) and 32 with oncocytomas. Results: Kiss-10 was detected in all patients and controls. SRT patients revealed significantly higher Kiss-10 levels than controls (mean value 10.04 vs. 6.37 pmol/l, p < 0.001). In SRT patients, Kiss-10 was detected at significantly different concentrations between the subgroups (p = 0.021). The highest concentration was observed in those with oncocytomas (11.50 pmol/) followed by chRCC, pRCC and ccRCC patients (9.89, 10.01 and 9.25 pmol/l, respectively). Receiver operating characteristic curve analyses revealed an area under the curve (AUC) of 0.82 for the comparison of all tumours vs. controls (p < 0.001) and an AUC of 0.671 for all malignant tumours vs. oncoytomas (p = 0.003). Conclusion: This study shows that Kiss-10 levels are significantly altered by malignancy and tumour subtypes even in patients with SRTs. Kiss-10 therefore deserves further attention as a plasmatic biomarker for renal tumours.

Background: The kidney is the most frequently transplanted human organ worldwide. In patients with end-stage renal failure, renal transplantation improves both quality of life and life expectancy. The current literature indicates that the numbers of renal recipients over 60 years of age has increased in recent years. Objectives: To evaluate the prevalence and management of lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO) in a contemporary series of male renal transplant (RTx) recipients. Materials and Methods: We retrospectively evaluated 150 consecutive transplant recipients at the University of Jena 12 months postoperatively for the presence and treatment of LUTS related to BPO. Results: The mean age of the patients was 59 years (range 27 - 82 years). By 12 months postoperatively, 91% (n = 137/150) were off dialysis with a functioning kidney graft. Two patients died during follow up. Six patients had undergone treatment for prostate cancer prior to RTx. Of the remaining 131 patients, 47% (n = 62/131) were considered as patients with BPO 12 months after RTx. Six percent (n = 8/131) of the patients experienced urinary retention due to BPO and 6% (n = 8/131) had a transurethral resection of the prostate (TURP) during the first year after RTx. No major complications were observed in those patients. A significant increase was noted in the use of α-blocker therapy after RTx (P = 0.004). Conclusions: We observed a high prevalence of LUTS related to BPO in our cohort of patients. Due to the increasing age of transplant recipients, more attention should be paid to the evaluation and treatment of BPO prior to RTx.

We present the first case study of idiopathic gigantic suprapubic lymphedema and buried penis treated with puboscrotal reconstruction in a patient with initial extreme obesity after an extensive weight reduction (120 kg). Massive localized lymphedema of the suprapubic region should be differentiated from the scrotal type. Severe lymphedema could not resolve on its own and weight reduction does not seem to be helpful in such cases.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.

The aim of this article is to analyse the long-term results of different surgical techniques for correction of penile deviations in Peyronie's disease. Patients who underwent surgery for a penile deviation in Peyronie's disease between 1997 and 2007 were included into this study. Cases were retrospectively analysed by chart review. The current situation was evaluated by a 16-item standardized questionnaire addressing penile straightness, sensation, length, sexual function and satisfaction. Ninety patients were contacted with a return rate of 75 (83%) evaluable questionnaires. Thirty-two patients were operated by shortening techniques (STs) with either Schroeder–Essed (n=16) or Nesbit (n=16). Forty-three were operated by a plaque in-/excision and defect covering by TachoSil method (TM). Both groups were similar regarding age (ST 56 years, TM 57 years), comorbidities, mean preoperative erection hardness score (EHS; 3.1 ST, 3.4 TM) and time of follow-up (total mean, 63 months). Preoperatively ST patients had significantly less plaques (P

The aim of the study was to investigate whether combinations of urine-based tumour markers including urinary cytology (Cytology or Cyt) increase the sensitivity in the detection of bladder cancer recurrence.Urinary cytology, NMP22, UroVysion (FISH) and ImmunoCyt (uCyt+) were determined in 221 patients during the follow-up of non-muscle-invasive transitional cell carcinoma (NMI TCC) before cystoscopy (n = 49) or with the suspicion of TCC recurrence before transurethral resection of the bladder (n = 173). For all markers alone as well as in all possible combinations (multimarker panels, MPs) sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were evaluated. MPs were considered positive if at least one marker was positive.No malignancy was found in 108 patients, whereas recurrent TCC was confirmed in 113 patients. Sensitivity and specificity for Cytology were 84% and 62%, for NMP22 68% and 49%, for FISH 72% and 63%, and for uCyt+ 73% and 62%, respectively. The NPV was below 80% for all markers alone. Combinations of two and three markers increased the sensitivity as well as the NPV to over 90 and 80%, by reducing specificity to an average of 44% and 35%, respectively. The most sensitive combinations were NMP22, uCyt+ together with Cytology and FISH, and uCyt+ together with NMP22 (sensitivity for both combinations 98%). There was no further improvement when all four markers were combined.Combinations of tumour markers increased the sensitivity and NPV in the detection of recurrence of NMI TCC. A stepwise approach of tumour marker determination may be used to reduce the frequency of follow-up cystoscopies at a reasonable risk.

Foreign bodies of the urinary tract represent a urologic emergency. First-line treatment is endoscopic removal, but this is often impeded by restricted space, especially in the urethra. We postulated that foreign objects could be fragmented by Holmium:YAG laser and investigated its effect on objects of varying composition.In a specially designed stage flushed with physiologic saline, medical and non-medical objects of differing composition and diameter were subjected to fragmentation by Holmium:YAG at powers of 18 and 30 W. In additional thermal experiments, 5,000 J was applied to differing volumes of 0.9% sodium chloride. Experiments were repeated ten times.With one exception (16 Ch silicon catheter) all medical objects were fragmented (latex urinary catheter, ureteral stents, and guidewires). Of non-medical objects (wood, steel, copper, graphite, and nylon) only copper wire was not amenable to laser dissection. These in vitro results were applied in two patients who presented with a pencil (wood and graphite) in the urethra or bladder. After Holmium:YAG laser fragmentation, the pencil could be removed by forceps each.Foreign objects in the urinary tract can be fragmented with a Holmium:YAG laser. When foreign bodies are too big for initial endoscopic extraction, the clinician should consider this technique as a reasonable and atraumatic option to avoid open surgery.

A higher incidence of bladder cancer has been reported in men compared with women. Clinical gender differences have been observed but are less well described.This retrospective analysis further examines clinical differences in the development and manifestation of bladder cancer between men and women.Consecutive male and female patients with bladder cancer treated between 1969 and 1997 at a single center (University Hospital of Innsbruck, Innsbruck, Austria) were included in the study. Patient characteristics regarding age, tumor classification, localization, and recurrence were compared between male and female patients. Statistical analysis was conducted using the t test, the chi(2) test, and the Kaplan-Meier method, with the log-rank test for subgroup analysis.In the 1,269 patients (876 men, 393 women) who were examined, 1,744 tumors were found. The male-to-female bladder cancer incidence ratio was 2.2:1. Tumors were diagnosed at a significantly younger age in men than in women (mean age: 62 years vs 67 years, respectively; P0.001). No difference in the histology of tumors was observed between the sexes. Muscle-invasive tumors more frequently occurred in men than in women (39.8% vs 34.5%; P = NS). In men compared with women, primary tumors were more aggressive (grade 2, 36.6% vs 28.2%; P0.001) and tumor recurrences were more invasive (59.0% vs 57.8%; P = NS). Tumors were more often located in the urethra in men than in women (43 [3.4%] vs 9 [1.8%]; P = 0.034), the trigonum (246 [19.8%] vs 75 [14.9%]; P0.001), and the bladder dome or vault (128 [10.3%] vs 37 [7.4%]; P = 0.015). Generally, no difference in survival rate was observed between the sexes; only in the subgroup of muscle-invasive tumors (n = 455) did women have a worse overall survival rate than did men (P = 0.022).Clinical gender differences in bladder cancer appear to have a higher incidence in men than in women. In this analysis, women were older at the age of detection, but had less-invasive and less-aggressive tumors than did men. However, women with muscle-invasive disease had a worse overall survival rate than did men in the same subset.

The technique for radical cystectomy in women is described, with special consideration given to the pelvic anatomy, and the urethra- and nerve-sparing approach in female patients. Advances in understanding female pelvic anatomy, following detailed animal, cadaveric and clinical studies, merged to give a better intraoperative identification of the sphincteric apparatus and neurovascular structures. Respecting the oncological premises, cystectomy in female patients can be done with a nerve-sparing technique. In rare cases the entire inner genitalia, including the anterior vaginal wall, can be preserved, which might lead to improved functional results with greater patient satisfaction. However, the oncological result should never be endangered by organ preservation.

INTRODUCTION AND OBJECTIVES: Plasmatic Kisspeptin is associated with malignancy and tumour progression. We evaluated Kisspetin in patients with small renal tumours (SRT) and controls as a potential marker for malignancy and subtype differentiation. METHODS: Kisspeptin was measured in preoperative plasma samples in a cohort of 143 patients with unilateral renal tumours smaller than 4 cm and 40 age matched controls by competitive ELISA test kits (Pheonix Europe GmbH, Karlsruhe). The cohort of patients included 56 patients with ccRCC, 43 with pRCC, 12 with chRCC and 32 oncocytomas. Comparisons were performed by the Kruksal-Wallis-test, the Mann-Whitney-U test and ROC curve analysis. RESULTS: Kisspeptin was detected in all patients and controls. SRT patients revealed significantly higher Kisspeptin levels than controls (mean value 5.02 pmol/l vs. 3.19 pmol/l, p1⁄40.005). In SRT patients Kisspeptin was detected at significantly different concentrations between the subgroups (p1⁄40.021). The highest concentration was observed in oncocytoma (mean value 5.75 pmol/) followed by pRCC, chRCC and ccRCC patients (5.01 pmol/l, 4.94 pmol/l and 4.63 pmol/l, respectively). Kisspeptin did not correlate to age, gender and tumour volume, except for oncocytomas, in which it significantly correlated to tumour volume (p1⁄40.026) and in ccRCCs, in which it significantly correlated to tumour grade with lower levels in high grade tumours (p1⁄40.004). ROC curve analyses revealed an AUC of 0.820 for the comparison of all tumours vs. controls (p

With a new generation of flexible ureterorenoscopes, a new area in stone management is emerging. Limitation of vision with these new instruments is often caused by insufficient irrigation flow, especially when using instruments like stone baskets, resulting from partial obstruction of the working and irrigation channel with these instruments. Empirically, new available smaller stone baskets seem to dramatically improve irrigation and therefore vision in clinical use. The goal of this study was to show objective differences in basket diameters and flow rates in an in vitro setting. Diameters and irrigation flows in flexible ureterorenoscopes depending on different sizes of stone baskets (Fr. 1.5-1.7-1.9-2.2-2.4-3.0) and different deflections were measured. The measured diameter of the baskets varied within the first 20 cm and the true measured size varied from the manufacturer's specified size to a different extent. The new generation of 1.5 and 1.7 Fr. baskets improved irrigation flow, even compared to the smallest commonly used baskets, up to 68%. Interestingly, deflection did not influence irrigation flow. This study confirmed the subjective impression of inadequate description of relevant basket diameters as well as that of a significant improvement of irrigation flow with the newest generation of stone baskets with smaller diameters.

Objective To prospectively evaluate the role of fluorescence-guided cystoscopy in a high-risk bladder cancer population undergoing screening based on a multi-marker panel of urine-tests (UroScreen-study). Patients and methods UroScreen was conducted as a validation study for tumor markers within the frame of a health surveillance program of workers with occupational exposure to aromatic amines. Voluntary annual screens were done in 1,609 men. Cytology, quantitative NMP22® assay, and UroVysion (FISH) were applied to 7091 urine samples. Subjects with at least one positive urine-based tumor marker and/or persisting microscopic hematuria were offered fluorescence-guided (PDD) instead of white light cystoscopy. In case of suspicious findings histopathological evaluation by transurethral biopsy was performed. Data were statistically summarized and compared to tumors found by the standard algorithm of the screening study. Results Twenty-two subjects with a mean age of 58 years (39–72) underwent PDD cystoscopy. Of those 3 had positive NMP22 tests, 14 positive FISH tests and 9 suspicious cytologies. Two had persisting microscopic hematuria only. PDD cystoscopy revealed enhanced unifocal fluorescence in 14. All had subsequent transurethral biopsy or resection. In total, 1 urothelial carcinoma (pTaG1, low grade) was diagnosed. In the other participants urothelial cancer of the bladder was ruled out. Chronic cystitis was revealed in 8 of 14 biopsies. No higher detection rate was found using PDD than with the standard algorithm of the UroScreen study in which 17 tumors were detected by white light cystoscopy. Conclusion The use of PDD does not lead to a higher cancer detection rate in a high-risk screening population. Larger sample sizes may be needed to ultimately asses the value of PDD for bladder cancer screening.

165 patients of whom 26 (15%) developed de novo bladder cancer following upper-tract surgery. A variety of salvage upper-tract therapies were utilized, although the majority of cases progressed to nephroureterectomy. 5-year cancer specific survival was dependent on primary tumor pathology and ranged between 50% and 100%. CONCLUSIONS: Pooled analysis of the literature highlights that approximately 15% of patients will suffer ipsilateral upper-tract or bladder recurrences after segmental resection of ureteral or renal pelvic tumors. These rates of recurrence should be discussed prior to surgery and underscore the need for vigilant post-operative surveillance.

The aim of our prospective designed study was to confirm the intra-observer agreement of assessments of the hydronephrosis index (HI) with a sonographic technique that potentially provides additional information in patients with acute renal colic (ARC). Sonographic measurement of HI and valuation of common clinical criteria were performed in 44 consecutive patients presenting with unilateral stone-related ARC. HI of colic side was recorded twice in predefined time intervals. Intra-observer agreement was evaluated with the Spearman’s rank correlation/rho (ρ) for attributive-metric characteristics. Data of HI-measurement on the colic side were compared with data of the unaffected side using t test. Intra-observer agreement was significant for HI in the colic side (ρ = 0.918, p

In recent years, mini-percutaneous nephrolitholapaxy (mini-PCNL) has gained popularity because of its reduced invasiveness. To improve clinical outcomes further, research is ongoing in selected centers. Important areas of interest include extravasation into the retroperitoneal space, acute absorption syndrome, and septicemia. The aim of this experimental study was to test a new 18F nephroscope sheath specially designed to decrease intrapelvic pressure during mini-PCNL whatever the irrigation pressure. In addition, the hydrodynamic effects of this device can be used for suction and removal of the stone fragments, in contrast to a standard Amplatz sheath.In a fresh, perfused cadaveric porcine kidney model, the new sheath was compared with a conventional sheath (control) with closed and open Luer-Lok outflow under increasing irrigation pressure. Intrarenal pressure peaks were measured with a urodynamic workstation. The irrigation fluid was marked with an ink that stains only endoluminal surfaces, and a post-measurement histopathologic work-up was performed to evaluate the changes on a morphologic level.Closing of the control sheath resulted in an increase in the intrapelvic pressure to a maximum of 136 cm H2O. Using the new sheath with a constant output flow made possible by its open proximal end, the maximal intrapelvic pressure remained low at 20 cm H2O, even when the inflow pressure reached 125 cm H2O. The ink distribution on the hematoxylin and eosin-stained slides reflected the results of the pressure measurements.Newly designed nephroscope sheaths with an open proximal end, such as the one described here, decrease the intrapelvic pressure compared with a closed outflow system. As a result, strict fluid control during the intervention is not necessary.