A self-supervised vision transformer to predict survival from histopathology in renal cell carcinoma.

PURPOSE: To develop and validate an interpretable deep learning model to predict overall and disease-specific survival (OS/DSS) in clear cell renal cell carcinoma (ccRCC). METHODS: Digitised haematoxylin and eosin-stained slides from The Cancer Genome Atlas were used as a training set for a vision transformer (ViT) to extract image features with a self-supervised model called DINO (self-distillation with no labels). Extracted features were used in Cox regression models to prognosticate OS and DSS. Kaplan-Meier for univariable evaluation and Cox regression analyses for multivariable evaluation of the DINO-ViT risk groups were performed for prediction of OS and DSS. For validation, a cohort from a tertiary care centre was used. RESULTS: A significant risk stratification was achieved in univariable analysis for OS and DSS in the training (n = 443, log rank test, p < 0.01) and validation set (n = 266, p < 0.01). In multivariable analysis, including age, metastatic status, tumour size and grading, the DINO-ViT risk stratification was a significant predictor for OS (hazard ratio [HR] 3.03; 95%-confidence interval [95%-CI] 2.11-4.35; p < 0.01) and DSS (HR 4.90; 95%-CI 2.78-8.64; p < 0.01) in the training set but only for DSS in the validation set (HR 2.31; 95%-CI 1.15-4.65; p = 0.02). DINO-ViT visualisation showed that features were mainly extracted from nuclei, cytoplasm, and peritumoural stroma, demonstrating good interpretability. CONCLUSION: The DINO-ViT can identify high-risk patients using histological images of ccRCC. This model might improve individual risk-adapted renal cancer therapy in the future.

Predicting Complexity in Transurethral Resection of Bladder Tumours: External Validation and Modification of the Bladder Complexity Score.

INTRODUCTION: First external validation of the Bladder Complexity Score (BCS) for predicting complex transurethral resection of bladder tumours (TURBT). METHODS: For BCS calculation, TURBTs performed at our institution between January 2018 and December 2019 were reviewed for the presence of preoperative characteristics listed in the Bladder Complexity Checklist (BCC). Receiver operating characteristics (ROC) analysis was used for BCS validation. To establish a modified BCS (mBCS) with maximum area under the curve (AUC), multivariable logistic regression (MLR) analysis was performed with all BCC-characteristics for different definitions of complex TURBT. RESULTS: 723 TURBTs were included in statistical analyses. Cohort's mean BCS was 11.2 ± 2.4 points (range: 5.5-22 points). In ROC analysis, BCS could not predict complex TURBT (AUC 0.573 [95% CI: 0.517-0.628]). MLR identified tumour size (OR 2.662, p < 0.001), and tumour number > 10 (OR 6.390, p = 0.032) as sole predictors for the modified endpoint of complex TURBT defined as a procedure meeting > 1 criterion: incomplete resection, surgery > 1 h, intraoperative complication, postoperative complications Clavien-Dindo ≥ III. mBCS increased the prediction to an AUC of 0.770 (95% CI: 0.667-0.874). CONCLUSION: In this first external validation, BCS remained an insufficient predictor of complex TURBT. mBCS requires reduced parameters, is more predictive and easier to apply in clinical practice.

Prospective, Randomized Comparative Evaluation of a Novel Hands-On Endourology Training Curriculum.

INTRODUCTION: The aim of this randomised prospective trial was to evaluate a novel hands-on endourological training programme (HTP) and compare it to the standard endourological colloquium (SC). METHODS: A new HTP was created based on a sequence of theoretical, video-based, and practical elements emphasising contemporary teaching methods. An existing SC in which live endourological operations were attended served as a comparison. Medical students were enrolled in a ratio of 1:2 (SC:HTP). Objective knowledge questionnaires (5 questions, open answers) and subjective Likert-type questionnaires (rating 1-3 vs. 4-5) were used for evaluation. Primary endpoint was urological knowledge transfer; secondary endpoints were learning effects, progression, and urological interest. RESULTS: 167 students (SC n = 52, HTP n = 115) were included. The knowledge assessment showed a significant increase in knowledge transfer benefitting the HTP on all 5 surveyed items (mean: n = 4/5/4/3/2 vs. n = 2/3/1/1, p < 0.0001). Interest and duration of the course were rated significantly more positively by HTP students (100.0/95.0% vs. 85.0/70.0%, p < 0.0001). The HTP students were significantly more confident in performing a cystoscopy independently (HTP 43.5% vs. SC 11.5%, p < 0.0001) and significantly claimed more often to have gained interdisciplinary and urological skills during the course (HTP 90.0/96.5% vs. SC 23.1/82.7%, p < 0.0001/p = 0.003). HTP students were also more likely to take the course again (HTP 98.2% vs. SC 59.6%, p < 0.0001). CONCLUSION: Modifying endourological teaching towards hands-on teaching resulted in stronger course interest, greater confidence regarding endourologic procedures, and significantly increased urologic knowledge transfer.

Upper Tract Urinary Cancer Recurrence after Radical Cystectomy: Risk Assessment of Intraoperative Frozen Section.

INTRODUCTION: Upper tract urinary cancer recurrence (UTUCR) after radical cystectomy (RC) is outcome-limiting. Surgical recommendations on intraoperative performance of frozen section analysis (FSA) and management of positive ureteral margin (PUM) are lacking. METHODS: 634 RC cases were identified (2010-2018). In patients with PUM, sequential ureteral resections up to a negative margin were performed. We investigated the accuracy of FSA, significance of PUM, and identified risk factors (RFs) to stratify patients for UTUCR. RESULTS: FSA was performed in 355 patients, including a total of 693 ureters. FSA sensitivity was 0.93 and specificity 0.99. PUM conversion was possible in 52 (91.2%) cases. UTUCR occurred in 17 (4.8%) patients. Identified UTUCR RFs are non-muscle invasive bladder carcinoma (NMIBC) (OR 3.8, 95% confidence intervals [CI] 1.4-10.2, p = 0.008), multifocal bladder cancer in cystectomy specimen (OR 4.7, CI 1.1-20.8, p = 0.042), and recurrent NMIBC (OR 4.1, CI 1.5-10.9, p = 0.006). Risk-group stratification showed a six-fold increase in UTUCR risk (low-to high-risk). CONCLUSION: FSA is a sensitive and specific method to identify PUM. UTUCR occurs significantly more often in patients with recurrent, multifocal NMIBC at the time of RC. Patients can be risk stratified for UTUCR. In case of NMIBC-PUM, surgeons can safely opt for a kidney preserving strategy.

Phosphodiesterase SMPDL3B Gene Expression as Independent Outcome Prediction Marker in Localized Prostate Cancer.

Current outcome prediction markers for localized prostate cancer (PCa) are insufficient. The impact of the lipid-modifying Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) in PCa is unknown. Two cohorts of patients with PCa who underwent radical prostatectomy (n = 40, n = 56) and benign prostate hyperplasia (BPH) controls (n = 8, n = 11) were profiled for SMPDL3B expression with qRT-PCR. Publicly available PCa cohorts (Memorial Sloane Kettering Cancer Centre (MSKCC; n = 131, n = 29 controls) and The Cancer Genome Atlas (TCGA; n = 497, n = 53 controls)) served for validation. SMPDL3B's impact on proliferation and migration was analyzed in PC3 cells by siRNA knockdown. In both cohorts, a Gleason score and T stage independent significant overexpression of SMPDL3B was seen in PCa compared to BPH (p < 0.001 each). A lower expression of SMPDL3B was associated with a shorter overall survival (OS) (p = 0.005) in long term follow-up. A SMPDL3B overexpression in PCa tissue was confirmed in the validation cohorts (p < 0.001 each). In the TCGA patients with low SMPDL3B expression, biochemical recurrence-free survival (p = 0.011) and progression-free interval (p < 0.001) were shorter. Knockdown of SMPDL3B impaired PC3 cell migration but not proliferation (p = 0.0081). In summary, SMPLD3B is highly overexpressed in PCa tissue, is inversely associated with localized PCa prognosis, and impairs PCa cell migration.

An m6A-Driven Prognostic Marker Panel for Renal Cell Carcinoma Based on the First Transcriptome-Wide m6A-seq.

To date, only a single transcriptome-wide m6A sequencing study of clear cell renal cell carcinoma (ccRCC) has been reported, with no validation so far. Herein, by TCGA analysis of the KIRC cohort (n = 530 ccRCC; n = 72 normal), an external expression validation of 35 preidentified m6A targets was performed. Further in-depth expression stratification enabled assessment of m6A-driven key targets. Overall survival (OS) analysis and gene set enrichment analyses (GSEA) were conducted to assess their clinical and functional impact on ccRCC. In the hyper-up cluster significant upregulation was confirmed for NDUFA4L2, NXPH4, SAA1, and PLOD2 (40%) and in the hypo-up cluster for FCHSD1 (10%). Significant downregulation was observed for UMOD, ANK3, and CNTFR (27.3%) in the hypo-down cluster and for CHDH (25%) in the hyper-down cluster. In-depth expression stratification showed consistent dysregulation in ccRCC only for 11.67%: NDUFA4L2, NXPH4, and UMOD (NNU-panel). Patients with strong NNU panel dysregulation had significantly poorer OS (p = 0.0075). GSEA identified 13 associated and significantly upregulated gene sets (all p-values < 0.5; FDR < 0.25). External validation of the only available m6A sequencing in ccRCC consistently reduced dysregulated m6A-driven targets on the NNU panel with highly significant effects on OS. Epitranscriptomics are a promising target for developing novel therapies and for identifying prognostic markers for daily clinical practice.

Integrin Expression in Localized Prostate Cancer: A TCGA and MSKCC Cohort-based Exploratory In Silico Analysis.

BACKGROUND/AIM: Diagnostic and prognostic biomarkers in localized prostate cancer (PC) are insufficient. Treatment stratification relies on prostate-specific antigen, clinical tumor staging and International Society of Urological Pathology (ISUP) grading, whereas molecular profiling remains unused. Integrins (ITG) have an important function in bidirectional signaling and are associated with progression, proliferation, perineural invasion, angiogenesis, metastasis, neuroendocrine differentiation, and a more aggressive disease phenotype in PC. However, ITG subunit expression in localized PC and their utility as prognostic biomarkers has not yet been analyzed. This study aimed to fill this gap and provide a comprehensive overview of ITG expression as well as ITG utility as biomarkers. PATIENTS AND METHODS: The Cancer Genome Atlas (TCGA) and the Memorial Sloan Kettering Cancer Center (MSKCC) prostate adenocarcinoma cohorts were analyzed regarding ITG expression in correlation to ISUP, N- and American Joint Committee on Cancer (AJCC) stage and were correlated with disease-free survival (DFS). Statistical tests used included the Mann-Whitney U-test, logrank test and uni- and multivariable cox regression analyses. RESULTS: After grouping for ISUP (1 and 2 vs. 3-5), N0 vs. N1 and AJCC stage (≤2 vs. ≥3), multiple ITGs showed significant expression differences. The most consistent results were observed for ITGα4, ITGαX, ITGα11, ITGß2 and ITGα2. In multivariable cox regression, ITGα2, ITGα10, ITGαD, ITGαB2 (TCGA), ITGα11 and ITGß4 (MSKCC) were independent predictors of DFS. CONCLUSION: The utility of ITGs as PC biomarkers was herein shown.

Reinvestigating the clinical relevance of the m6A writer METTL3 in urothelial carcinoma of the bladder.

METTL3 is the major writer of N6-Methyladenosine (m6A) and has been associated with controversial roles in cancer. This is best illustrated in urothelial carcinoma of the bladder (UCB), where METTL3 was described to have both oncogenic and tumor-suppressive functions. Here, we reinvestigated the role of METTL3 in UCB. METTL3 knockout reduced the oncogenic phenotype and m6A levels of UCB cell lines. However, complete depletion of METTL3/m6A was not achieved due to selection of cells expressing alternative METTL3 isoforms. Systematic vulnerability and inhibitor response analyses suggested that uroepithelial cells depend on METTL3 for viability. Furthermore, expression and survival analyses of clinical data revealed a complex role for METTL3 in UCB, with decreased m6A mRNA levels in UCB tumors. Our results suggest that METTL3 expression may be a suitable diagnostic UCB biomarker, as the enzyme promotes UCB formation. However, the suitability of the enzyme as a therapeutic target should be evaluated carefully.

Changes in neutrophile-to-lymphocyte ratio as predictive and prognostic biomarker in metastatic prostate cancer treated with taxane-based chemotherapy.

OBJECTIVES: To assess the predictive and prognostic value of changes in longitudinal neutrophile-to-lymphocyte (NLR) ratios in men receiving taxane-based chemotherapy for metastatic prostate cancer (PC). METHODS: Retrospective, unicentric cohort study of patients treated with either docetaxel for metastatic hormone-sensitive PC (mHSPC) or docetaxel or cabazitaxel for metastatic castration-refractory PC (mCRPC) at a tertiary referral hospital between 2010 and 2019. NLR ratios were calculated for each cycle. Next, slopes over the first three (NLR3) and over six cycles (NLR6) were calculated and analysed for biochemical/radiologic response and survival. RESULTS: A total of 36 mHSPC (docetaxel), 118 mCRPC (docetaxel) and 38 mCRPC (cabazitaxel) patients were included. NLR3 was significantly associated with 1-year-survival, radiographic and biochemical response in mCRPC (docetaxel) in uni- and multivariable analyses. In mCRPC (docetaxel), positive NLR3s were associated with favourable 1-year-survival. CONCLUSION: This study demonstrated NLR3 as a prognostic marker in men receiving docetaxel for mCRPC. NLR3 might be a clinical tool to reflect the individual's response to taxane-based chemotherapy. Thereby, NLR3 could complement existing biomarkers and help to early identify treatment failure before complications arise. Further prospective and multicentric studies are needed to extend and confirm the presented results.

Deep learning can predict survival directly from histology in clear cell renal cell carcinoma.

For clear cell renal cell carcinoma (ccRCC) risk-dependent diagnostic and therapeutic algorithms are routinely implemented in clinical practice. Artificial intelligence-based image analysis has the potential to improve outcome prediction and thereby risk stratification. Thus, we investigated whether a convolutional neural network (CNN) can extract relevant image features from a representative hematoxylin and eosin-stained slide to predict 5-year overall survival (5y-OS) in ccRCC. The CNN was trained to predict 5y-OS in a binary manner using slides from TCGA and validated using an independent in-house cohort. Multivariable logistic regression was used to combine of the CNNs prediction and clinicopathological parameters. A mean balanced accuracy of 72.0% (standard deviation [SD] = 7.9%), sensitivity of 72.4% (SD = 10.6%), specificity of 71.7% (SD = 11.9%) and area under receiver operating characteristics curve (AUROC) of 0.75 (SD = 0.07) was achieved on the TCGA training set (n = 254 patients / WSIs) using 10-fold cross-validation. On the external validation cohort (n = 99 patients / WSIs), mean accuracy, sensitivity, specificity and AUROC were 65.5% (95%-confidence interval [CI]: 62.9-68.1%), 86.2% (95%-CI: 81.8-90.5%), 44.9% (95%-CI: 40.2-49.6%), and 0.70 (95%-CI: 0.69-0.71). A multivariable model including age, tumor stage and metastasis yielded an AUROC of 0.75 on the TCGA cohort. The inclusion of the CNN-based classification (Odds ratio = 4.86, 95%-CI: 2.70-8.75, p < 0.01) raised the AUROC to 0.81. On the validation cohort, both models showed an AUROC of 0.88. In univariable Cox regression, the CNN showed a hazard ratio of 3.69 (95%-CI: 2.60-5.23, p < 0.01) on TCGA and 2.13 (95%-CI: 0.92-4.94, p = 0.08) on external validation. The results demonstrate that the CNN's image-based prediction of survival is promising and thus this widely applicable technique should be further investigated with the aim of improving existing risk stratification in ccRCC.

Baseline Modified Glasgow Prognostic Score (mGPS) Predicts Radiologic Response and Overall Survival in Metastatic Hormone-sensitive Prostate Cancer Treated With Docetaxel Chemotherapy.

BACKGROUND/AIM: To assess the baseline inflammatory markers modified Glasgow Prognostic Score (mGPS), systemic immune-inflammation index (SII), and neutrophile-to-lymphocyte ratio (NLR) as pragmatic tools for predicting response to chemohormonal therapy (docetaxel plus ADT) and prognosis in men with metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS: Male patients who received docetaxel at a tertiary university care center between 2014 and 2019 were screened for completion of 6 cycles. NLR, SII, mGPS, overall survival (OS), three-year survival, and radiologic response were assessed. Complete response (CR), partial response (PR), and stable disease (SD) were analyzed alone and in combination. RESULTS: Thirty-six mHSPC-patients were included. In thirty patients, baseline mGPS was assessed and was either 0 (n=22) or 2 (n=8). In Cochran-Armitage Trend Test, mGPS showed significant association with the combined radiologic endpoint of "CR, PR, or SD" (p=0.01), three-year survival (p=0.02), and OS (p<0.01). Next to prostate-specific antigen (PSA) (HR per 100 units 1.16, 95%CI=1.04-1.30, p<0.01), NLR (HR=1.31, 95%CI=1.03-1.66, p=0.03), and mGPS (2 vs. 0, HR=6.53, 95%CI=1.6-27.0, p<0.01) at baseline showed significant association with OS in univariable cox regression. However, mGPS remained the only independent predictor for OS in multivariable cox regression (p<0.01) and for the combined radiologic endpoint of "CR, PR or SD" (p=0.01) in multivariable logistic regression. SII showed no statistical relevance. CONCLUSION: Baseline mGPS seems to be a pragmatic tool for clinical decision-making in patients with mHSPC in daily routine.

Endourological Training Using 3D-Printed Bladder Phantoms: Development and Prospective Evaluation.

Background: To create and evaluate a realistic, anatomically accurate, and user-friendly bladder phantom for reproducible endourological training purposes and endoscope mastery. Materials and Methods: The anatomy of full bladders was mapped from human computed tomography datasets. After a 3D model development process, content evidence and response process evidence (RPE) of the phantom were evaluated using the system usability scale (SUS), 5-point Likert scale questionnaires, and task execution of experienced urologists (U) and endoscopy-naive medical students (MS) in two training sessions (first vs second). Required validation cohort sizes (1:10) of the evaluating urologists (n = 12) and students (n = 115) were precalculated. Time measurements were recorded. Students were additionally evaluated by a validated global psychomotor assessment score (GPSS). Group comparisons were calculated by the Mann-Whitney U test. All tests were two sided with p < 0.05 considered statistically significant. Results: Content evidence was assessed by urologists with an "excellent" SUS score of 89.4 ± 5.9 and an average "agreement" of ≥4 pts in the Likert scale questionnaires. RPE was assessed by intra- and intergroup time comparison for the execution of endoscopic tasks (cystoscopy [CY], guidewire insertion, and tumor biopsy). For CY, U: first 17.6 ± 4.4 seconds vs second 12.4 ± 2.0 seconds, p = 0.002; MS: first 56.6 ± 28.2 seconds vs second 28.6 ± 14.7 seconds, p < 0.001; U vs MS: first U 17.6 ± 4.4 seconds vs first MS 56.6 ± 28.2 seconds, p < 0.001, second U 12.4 ± 2.0 seconds vs second MS 28.6 ± 14.7 seconds, p < 0.001. Significant time differences were documented for all tasks and sessions (p < 0.001). Additionally, significant GPSS differences were recorded between the sessions (GPSS: first 20.4 ± 5.1 pts vs second 24.7 ± 4.0 pts, p < 0.001). Conclusions: Our low-fidelity 3D-printed bladder, called BladCap, is an easy-to-assemble, inexpensive, and robust phantom. We present data, which establish construct validity to support use as a clinical training device.

The Comprehensive Complication Index for Advanced Monitoring of Complications Following Endoscopic Surgery of the Lower Urinary Tract.

Purpose: To evaluate the Comprehensive Complication Index (CCI) for reporting complications in lower urinary tract transurethral procedures and compare it with the Clavien-Dindo classification (CDC). Materials and Methods: A total of 450 consecutive patients were included into the analyses [150 each of transurethral resection of bladder tumors (TURBT), transurethral resection of the prostate (TURP), and transurethral enucleation of the prostate using Tm:YAG, (ThuLEP)]. Complications were assessed according to the modified CDC. The CCI was calculated using a freely accessible online tool. Descriptive statistics and correlation analyses were applied to quantify operational differences and length of stay (LOS) between CDC and CCI. Sample size calculations for hypothetical clinical trials were contrasted for CDC and CCI application. Results: Overall n = 150 patients with complications (33.3%) within the first 60 days after operation were identified. Of these, n = 125 (83.4%) were minor complications up to CDC grade IIIa. Of patients with complications, n = 57 patients (12.6%) experienced more than one complication. Here, the cumulative CCI led to an upgrade of at least one CDC grade in 33 patients. Hence, in 22.0% of cases, the highest CDC grade underestimated the degree of complications. CCI showed higher correlation with LOS compared with CDC (all r > 0.2, all p-values ≤0.0001). Using CCI instead of CDC for sample calculation resulted in a strong reduction of the required number of patients for all three interventions (percentage of patient number decrease: -93.2% for TURBT, -71.8% for TURP, and -81.1% for ThuLEP). Conclusion: The CCI gives a more precise interpretation of the postinterventional complications of TURBT, TURP, and ThuLEP. CCI application may reduce the required sample size for clinical trials and will relieve their recruitment in the future.

The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma.

Renal cell carcinoma (RCC) is the deadliest primary genitourinary malignancy typically associated with asymptomatic initial presentation and poorly predictable survival. Next to established risk factors, tumor microenvironment may alter metastatic capacity and immune landscape. Due to their high concentrations, sulfoglycolipids (sulfatides) were among the first well-described antigens in RCC that are associated with worse prognosis. As sulfatide detection in routine diagnostics is not possible, we aimed to test the prognostic value of its protein counterpart, sulfatide-producing enzyme Gal3ST1. We performed retrospective long-term follow up analysis of Gal3ST1 expression as prognostic risk factor in a representative RCC patient cohort. We observed differentially regulated Gal3ST1 expression in all RCC types, being significantly more associated with clear cell RCC than to chromophobe RCC (p = 0.001). Surprisingly, in contrast to published observations from in vitro models, we could not confirm an association between Gal3ST1 expression and a malignant clinical behaviour of the RCC. In our cohort, Gal3ST1 did not significantly influence progression-free survival (Hazard Ratio (HR): 1.7 95% CI (0.6-4.9), p = 0.327). Particularly after adjusting for histology, T-stage, N-status and M-status at baseline, we observed no independent prognostic effect (HR = 1.0 95% CI (0.3-3.3), p = 0.96). The analysis of Gal3ST1 mRNA expression in a TCGA dataset supported the results of our cohort. Thus, Gal3ST1 might help to differentiate between chromophobe RCC and other frequent RCC entities but-despite previously published data from cell culture models-does not qualify as a prognostic marker for RCC. Further investigation of regulatory mechanisms of sulfatide metabolism in human RCC microenvironment is necessary to understand the role of this quantitatively prominent glycosphingolipid in RCC progression.

Preoperative urine culture - Is it necessary to prevent infectious complications following ureterorenoscopy?

To prevent postoperative infectious complications, a urinary tract infection should be either diagnostically excluded or treated prior to ureterorenoscopy (URS). URS is a frequently performed endoscopic surgery for urological stone removal. Although the urinary dipstick test represents a simple and cost-effective method to gain information about the presence of urinary tract infection, the prevailing procedure is the more expensive and more time-consuming method of urine culture. The aim of this retrospective single-center study was to compare two strategies of perioperative prophylaxes prior to URS and to evaluate their impact on postoperative infectious complications: I) Obtaining a urine culture in every patient prior to URS or II) only in case of a positive dipstick test. Therefore, we retrospectively compared 201 patients in two cohorts undergoing URS. In one cohort a urine culture was obtained only in case of a positive dipstick test of midstream urine sample and in the second cohort a urine culture was prepared for every patient regardless of the dipstick's test results. The study's end point was determined as "infectious failure" (IF), if more than one of the following criteria are fulfilled: postoperative fever, elevation of inflammation laboratory values, significant prolongation of hospital stay and readmission within short-notice. Simple and multiple logistic regressions were performed to evaluate the influence of patient characteristics and preoperative urine analysis strategy on the occurrence of IF. Patients with a score of the American Society of Anesthesiologists (ASA) > 2 had a nearly statistically higher risk (p = .09) to develop an IF than healthier patients with an ASA score ≤ 2. Prestenting was determined as a significant predictive factor (p = .04) for a postoperative IF. No difference in patients with or without IF was detected regarding the two preoperative urine analysis strategies. Sensitivity of dipstick test was 87.5% and the negative predictive value was 89.66%. We found that a negative urine dipstick test result obtained prior to URS eliminated the need for urine culturing in predicting postoperative infectious complication. This approach can reduce preoperative preparation-time and costs without affecting postoperative complication outcomes.

Chronic Kidney Disease After Partial Nephrectomy in Patients With Preoperative Inconspicuous Renal Function - Curiosity or Relevant Issue?

BACKGROUND: Chronic kidney disease (CKD) is a severe long-term complication after partial nephrectomy (PN). Clinical and scientific focus lies on patients with impaired renal function at the time of surgery. Little data is available on patients with normal preoperative renal function (NPRF). PATIENTS AND METHODS: Patients who underwent PN with a preoperative estimated glomular filtration rate > 60 mL/min/1.73m2 were retrospectively examined at 8 European urologic centers. The occurrence of new onset CKD ≥ stage III after surgery (sCKD) was defined as the primary endpoint. Group comparisons and risk correlations were determined. Based on this data, a risk stratification model for sCKD was developed. RESULTS: Of the 1315 patients with NPRF included, 249 (18.9%) developed sCKD after a median follow-up of 44 months (range, 6-255 months). Pair analysis and univariable regression revealed age, arterial hypertension, American Society of Anesthesiologists score, tumor stage, surgical approach, intraoperative blood loss, perioperative blood transfusions and preoperative CKD stage as predictors for sCKD development. Multivariate analysis confirmed perioperative blood transfusion (hazard ratio [HR], 2.96; P ≤ .0001), age (≥ 55 years; HR, 2.60; P = .0002), tumor stage (> pT1; HR, 2.15; P = .025), and preoperative CKD stage (stage II vs. I; HR, 3.85; P ≤ .0001) as independent risk factors. A model that stratified patient risk for new onset CKD was highly significant (P < .0001). CONCLUSION: Every fifth patient with NPRF developed sCKD following PN. Elderly patients with higher tumor stage and who require blood transfusion appear to be at increased risk. Based on our risk stratification, patients with ≥ 2 risk factors are candidates for an early, nephrologic follow-up.

Preclinical and Clinical Evaluation of a Novel, Variable-View, Rigid Endoscope for Female Cystoscopy.

OBJECTIVE: To evaluate the preclinical and clinical performance of the pivoting lens rigid Endocameleon (ECAM) endoscope in white light cystoscopy (WLC). MATERIALS AND METHODS: Preclinical evaluation was performed ex vivo in CT-based, anatomically accurate and validated bladder phantoms. Six defined tasks with objective endpoints were compared between ECAM-WLC and rigid WLC (30° view angle, rWLC) in 30 interventions. Subsequently, the comparison was transferred to in vivo n = 21 interventions. A validated usability score (System Usability Scale, SUS) as well as physician and patient-related outcomes were assessed using Likert-scale-based questionnaires. Intra- and postinterventional complications were recorded according to the Clavien-Dindo classification. RESULTS: The ex vivo evaluation showed a significant superiority of ECAM-WLC in 4 of 6 endoscopic tasks. Noteworthy is the lower pressure on the bladder neck due to the endoscopesalteration of the endoscope (4/60 vs 17/60, P <.0001) and a more precise imaging of all bladder regions (22/30 vs 30/30, P = .046), including the anterior wall (0/30 vs 28/30, P <.0001). In vivo, surgeons rated the ECAM-WLC with an "excellent" SUS of 86.79%, also expressing that ECAM-WLC would enhance bladder surface visualization (4.52/5.0 ± 0.51), with a preferred use for ECAM-WLC during their next cystoscopy (4.62 ± 0.50). Patients reported ECAM-WLC to be less painful (4.5/5.0 ± 0.84) compared to rWLC. No intervention-related complications were observed. CONCLUSION: ECAM-WLC is a safe and accessible procedure that could improve conventional diagnostic WLC by combination of the advantages of fWLC and rWLC.

YRNA Expression Profiles are Altered in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Noncoding RNAs play an important role in human carcinogenesis. YRNAs, a novel class of noncoding RNAs, have been identified as biomarkers in breast cancer patients. OBJECTIVE: To test the hypothesis that YRNA expression is dysregulated in clear cell renal cell carcinoma (ccRCC). DESIGN, SETTING, AND PARTICIPANTS: We first measured the expression of all known YRNAs (hY1, hY3, hY4, and hY5) in a screening cohort (30 ccRCC and 15 normal renal tissues). Subsequently, hY3 and hY4 were validated in an independent cohort (88 ccRCC and 59 normal renal tissues). Finally, hY3 and hY4 levels in serum samples from 30 ccRCC and 15 control individuals were measured. YRNAs were detected using quantitative real-time polymerase chain reaction. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relative expression values were analyzed using the Mann-Whitney-U test and Kaplan Meier estimates. RESULTS AND LIMITATIONS: Expression of hY3 and hY4 was increased in ccRCC samples compared with normal renal tissue, whereas hY1 and hY5 levels were similar. Expression levels of hY4 correlated with ccRCC stage and the presence of lymph node metastases. Neither hY3 nor hY4 were circulating at different levels in ccRCC patients and control individuals. CONCLUSIONS: The expression of hY3 and hY4 is altered in ccRCC and associated with advanced disease. PATIENT SUMMARY: In this report we studied the expression of noncoding YRNA in clear cell renal cell carcinoma tissue. We observed increased hY3 and hY4 expression levels in cancer tissues. However, expression levels were not different in the serum of patients with cancer or benign disease.

Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma.

Small non-coding RNAs (sncRNA; <200 nt) regulate various cellular processes and modify gene expression. Under nutritional, biological or physiochemical stress some mature sncRNAs (e.g. tRNAs) are cleaved into halves (30-50 nt) and smaller fragments (18-22 nt); the significance and functional role of these tRNA fragments is unknown, but their existence has been linked to carcinogenesis. We used small RNA sequencing to determine the expression of sncRNAs. Subsequently the findings were validated for miR-122-5p, miR-142-3p and 5'tRNA4-Val-AAC using qPCR. We identified differential expression of 132 miRNAs (upregulated: 61, downregulated: 71) and 32 tRNAs (upregulated: 13, downregulated: 19). Read length analysis showed that miRNAs mapped in the 20-24 nt fraction, whereas tRNA reads mapped in the 30-36 nt fraction instead the expected size of 73-95 nt thereby indicating cleavage of tRNAs. Overexpression of miR-122-5p and miR-142-3p as well as downregulation of 5'tRNA4-Val-AAC was validated in an independent cohort of 118 ccRCC and 74 normal renal tissues. Furthermore, staging and grading was inversely correlated with the 5'tRNA4-Val-AAC expression. Serum levels of miR-122-5p, miR-142-3p and 5'tRNA4-Val-AAC did not differ in ccRCC and control subjects. In conclusion, 5' cleavage of tRNAs occurs in ccRCC, but the exact functional implication of tRNA-halve deregulation remains to be clarified.