Additional Value of Mini-Cog© in Urogeriatric Patients Concurrently Screened by G8 Scores.

Background: Cognitive impairment is poorly addressed in G8 screening. The aim of the present study was to evaluate the additional value of Mini-Cog© in urogeriatric patients concurrently screened by G8 scores. Methods: Seventy-four consecutive urogeriatric patients aged 75 and above were evaluated. All patients underwent G8 and Mini-Cog© screening. Patients with a G8 score above 14 were considered geriatric "healthy or fit". A Mini-Cog© from 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 the Mini-Cog© screening. Results: The mean age of the patients was 83 y (min. 75-max. 102). Sixty-one of the patients were males, and 13 were females. Twenty-nine of the patients had a normal G8 score and were considered "healthy or fit", and 45 were not. Forty-three of the patients had an inconspicuous Mini-Cog©, and 31 had 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, five patients had a Mini-Cog© of less than four points, which is suspicious for cognitive disorders. Furthermore, of the 43 patients with a normal G8 subscore in item "E" of two points, 6 patients had a conspicuous Mini-Cog© of less than four points. Conclusions: As shown by the present study, the Mini-Cog© might extend 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.

[Surgical treatment of urethral prolapse]. / Chirurgische Therapie des Urethralprolaps.

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.

Comparison of G8 and ISAR Screening Results in Geriatric Urology.

BACKGROUND: The G8 and ISAR scores are two different screening tools for geriatric risk factors and frailty. The aim of this study was to compare the G8 and ISAR screening results in a cohort of urogeriatric patients to help clinicians to better understand and choose between the two tests. METHODS: We retrospectively evaluated 100 patients at the age of 75 and above who were treated for different urological conditions. All routinely and prospectively underwent G8 and ISAR screening tests. A G8 score ≤ 14 and an ISAR score > 2 were considered positive. The results for the two tests were compared and correlated to clinical data. RESULTS: The mean age of the patients was 83 y (min. 75-max. 101); 78 of the patients were male, while 22 were female; 58 of the patients were G8-positive, while 42 were G8-negative; and 24 were ISAR-positive, while 76 ISAR were negative. All the ISAR-positive patients were also G8-positive. There was a significant negative correlation between the G8 and ISAR scores (r = -0.77, p < 0.001). Both tests correlated significantly with the Charlson comorbidity index, length of stay, number of coded diagnosis, and Braden score (p < 0.05). CONCLUSION: Both tests are significantly correlated with each other and to clinical data related to geriatric frailty. However, the G8 score has a much higher rate of positive tests, which limits its use in daily routine, and the ISAR score is therefore preferable. For "fit" geriatric patients, however, a negative G8 score can be of great use as a confirmatory test for further decision making.

[What do urologist do in daily practice? : A first "unfiltered" look at patient care]. / Was machen Urologen in der Praxis? : Ein erster "ungefilterter" Blick auf die Versorgung.

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.

An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.

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.

[The G8 questionnaire as a geriatric screening tool in urooncology]. / Der G8-Fragebogen als geriatrisches Screening-Tool in der Uroonkologie.

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.

Utility of the EORTC risk tables and CUETO scoring model for predicting recurrence and progression in non-muscle-invasive bladder cancer patients treated with routine second transurethral resection.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Improved predictive tools should be developed for optimal treatment selection.

[Intra- and postoperative complications classified according to the Clavien-Dindo classification in patients > 80 years after transurethral resection of the urinary bladder]. / Intra- und postoperative Komplikationen klassifiziert nach Clavien Dindo bei Patienten > 80 J. nach transurethraler Resektion der Harnblase.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups.

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.

Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study.

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 (p<0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guérin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p<0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p<0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R2=0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/750 patients). CONCLUSIONS: 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.

Urinary transcript quantitation of CK20 and IGF2 for the non-invasive bladder cancer detection.

PURPOSE: 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). METHODS: 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. RESULTS: Relative transcript levels were significantly elevated 3.4/11-fold for CK20 and 188/64-fold for IGF2 (p < 0.001) in urine sediments of BCa patients compared to controls in the TC and VC, respectively. In a combined analysis, the resulting sensitivity (SN) (SNTC: 77.9; SNVC: 90.3%) and specificity (SP) (SPTC: 88.0; SPVC: 84.0%) were similar to that of VUC. The sensitivity of VUC in combination with CK20 and IGF2 was considerably increased (SNTC: 94.6; SNVC: 93.2%) while specificity was reduced (SPTC: 72.0; SPVC: 82.0%) compared to VUC alone in the test and validation cohort. CONCLUSIONS: Transcript levels of IGF2 and CK20 enabled the detection of BCa with a diagnostic performance similar to VUC. Combined analysis of voided urine cytology together with altered transcript levels of CK20 and IGF2 enhanced sensitivity, but did not improve overall test performance.

Evaluation of Plasmatic Kisspetin-10 as a Biomarker for Malignancy and Subtype Differentiation in Small Renal Tumours.

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.

Gigantic Suprapubic Lymphedema: A Case Study.

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.

Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma.

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.

Prevalence and Management of Lower Urinary Tract Symptoms Related to Benign Prostatic Obstruction in a Contemporary Series of Renal Transplant Recipients.

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.

High-grade Carcinoma of the Proximal Ureter With Negative Nephroureteroscopy Detected by a Positive FISH Test: A Rare Case Report.

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.