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To assess epidemiology, clinical presentation, treatment and overall survival of adult patients with renal sarcomas, the 2004-2016 SEER and NCDB databases were queried for adult patients diagnosed with renal sarcoma, calculating average annual age-adjusted incidence rates (AAIR) and average annual percentage change (AAPC) as well as overall survival (OS). In n = 1279 included renal sarcoma patients, AAIR remained constant over the study period (average 0.53 cases/1million; AAPC = 0.7, p = 0.6). Leiomyosarcoma (AAIR 0.14 cases/1 million) and malignant rhabdoid tumors (0.06 cases/1 million) were most common. Sarcoma histiotypes demonstrated considerable heterogeneity regarding demographic and cancer-related variables. Patients presented with advanced local extent (T3 33.3%; T4 14.2%) or distant metastases (29.1%) and commonly underwent surgical resection (81.6%). Longer OS was independently associated with younger age, female sex, lower comorbidity index, low T stage, negative surgical margins, absence of tumor necrosis or distant metastases and leiomyosarcoma histiotype (multivariable p < 0.05 each). Treatment efficacy varied according to sarcoma histiotype (interaction p < 0.001). Accounting for 0.25% of renal malignancies, renal sarcomas include 43 histiotypes with distinct epidemiology, clinical presentation, outcomes and sensitivity to systemic therapy, thereby reflecting soft-tissue sarcoma behavior. Renal sarcoma treatment patterns follow recommendations by renal cancer guidelines with surgical resection as the cornerstone of therapy., (© 2024. The Author(s).)

Background: In addition to the objectifiable treatment quality, patients' perspectives are gaining relevance., Objective: This study aimed to characterize available hospital rating websites (HRW) with regards to patient ratings and to compare them with data from hospital quality reports and quality assurance based on routine data (QSR) for urological departments., Materials and Methods: After a structured online search for HRWs, websites were compared based on patient ratings from the 10 urologic departments with the largest intervention rates in 2021 using generalized estimated equations. For radical prostatectomy (RPE), quantitative comparison of patient ratings (klinikbewertungen.de) and QSR-based ratings was performed using Spearman's rank correlation., Results: Of 1845 hits, 25 portals were analyzed. The department-wise comparison of HRWs resulted in significantly different patient ratings (p < 0.001). Patient ratings (klinikbewertungen.de) and QSR data (AOK-Gesundheitsnavigator) showed no significant correlation. An internal comparison of QSR data and patient ratings from the AOK-Gesundheitsnavigator on RPE showed a significant negative correlation between the overall rating and unplanned reoperations (r = -0.81) or other complications (r = -0.91). There was no significant correlation with the recommendation rate by patients., Conclusion: Hospital rating websites show considerable heterogeneity regarding patient ratings of the same urology department in different portals. Furthermore, based on the selected examples, there seems to be no correlation between subjective and objective evaluations between different websites or within one website., (© 2024. The Author(s).)

Aim and Objectives: We aimed to test the predictive value of readily accessible and easily performed post-surgical "bedside tests" on their validity of long-term urinary incontinence (UI) (≥12 months) in patients following robot-assisted laparoscopic radical prostatectomy (RALP). Material and Methods: Patients undergoing RALP between July 2020 and March 2021 were prospectively included and subdivided into two groups based on their pad usage after 12 months (0 vs. ≥1 pad). After catheter removal, patients performed a 1 h pad test, documented the need for pad change in a micturition protocol and received post-voiding residual urine volume ultrasound. Univariate and multivariable analyses were used to demonstrate the predictive value of easily accessible tests applied after catheter removal for UI following RALP. Results: Of 109 patients, 47 (43%) had to use at least one pad (vs. 62 (57%) zero pads) after 12 months. Univariate testing showed a significant difference in urine loss between both groups evaluated by the 1 h pad test performed within 24 h after catheter removal (70% < 10 mL, vs. 30% ≥ 10 mL, p = 0.004) and in the need for pad change within the first 24 h after catheter removal (14% dry pads vs. 86% wet pads, p = 0.003). In multivariable analyses, the combination of both tests (synoptical incontinence score) could be confirmed as an independent predictor for UI after 12 months ( p = 0.011). Conclusions: Readily accessible "everyday" diagnostics (pad test/change of pads after catheter removal) following RALP seem to be associated with a higher rate of long-term UI. This finding is crucial since patients with a potentially higher need for patient education and counselling can be identified using these readily accessible tests. This could lead to a higher patient satisfaction and improved outcomes.

Purpose: The aim of the study was to examine the influence of the surgical approach for robot-assisted laparoscopic prostatectomy (RALP) on long-term urinary continence status in the era of self-reported functional status measures using the Expanded Prostate Cancer Index Composite 26., Materials and Methods: This is a prospective evaluation of 232 patients undergoing RALP between September, 2019 and September, 2020. Urinary continence status and postoperative incontinence (pad usage) were evaluated 12 months after RALP using Expanded Prostate Cancer Index Composite 26 questionnaires. Patients were categorized according to their surgical approach and outcome into the following groups: successful nerve sparing (NS), primarily without nerve sparing (prim. NNS), and no nerve sparing by secondary resection (NNS by SR). The median levels of their questionnaire outcomes were evaluated and compared using the Wilcoxon rank sum test with continuity correction., Results: Urinary continence status 12 months after RALP differed significantly between the NS and prim. NNS ( p = 0.0071) and the NS and NNS by SR ( p = 0.0076) groups. There was no significant difference between the prim. NNS and NNS by SR ( p = 0.53) groups. Pad usage 12 months after RALP had no significant difference with regard to SR of the neurovascular bundle ( p = 0.14)., Conclusions: Patient-reported outcomes of long-term urinary continence status seem to show no difference in postoperative continence, regardless of whether a non-nerve-sparing result was planned or reached through SR. Instead, preservation of neurovascular bundle seems to lead to better long-term continence rates., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

Purpose: To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in "active surveillance (AS)" candidates refusing standard treatment options., Materials and Methods: IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure)., Results: Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure., Conclusions: Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Introduction: We evaluated the effectiveness and safety profile of the tyrosine kinase inhibitor sunitinib in patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting., Methods: We analyzed data of adult a/mRCC patients treated with sunitinib. Data were derived from the German non-interventional post-approval multicenter STAR-TOR registry (NCT00700258). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated using descriptive statistics and survival analyses for the entire cohort and patient subgroups., Results: A total of 116 study sites recruited 702 patients treated with sunitinib (73.1% male; median age 68.0 years; median Karnofsky index 90%) between November 2010 and May 2020. The most frequent histological subtype was clear cell RCC (81.6%). Sunitinib was administered as first-line treatment in 83.5%, as second line in 11.7%, and as third line or beyond in 4.8% of the patients. Drug-related AEs and serious AEs were reported in 66.3% and 13.9% of the patients, respectively (most common AE: gastrointestinal disorders; 39.7% of all patients)., Conclusions: This study adds further real-world evidence of the persisting relevance of sunitinib for patients with a/mRCC who cannot receive or tolerate immune checkpoint inhibitors. The study population includes a high proportion of patients with unfavorable MSKCC poor-risk score, but shows still good PFS and OS results, while the drug demonstrates a favorable safety profile. The STAR-TOR registry is also registered in the database of US library of medicine (NCT00700258)., (© 2024 S. Karger AG, Basel.)

We present the case of a 36-year-old man suffering from perianal loss of urine through a cutaneous pore while urinating. Appropriate diagnostic investigation showed a urethrocutaneous fistula of the prostatic urethra of unclear aetiology. Because of the patient's young age and sexual activity, surgical treatment was challenging. The fistula was isolated via a perineal access and ligated close to the prostate without endangering the neurovascular bundles. In order to achieve a secure closure of the fistula, a Gracilis flap was placed as an interposition between the dorsal prostate and the percutaneous fistula outlet. To date, no case has been described of a successful, function-preserving surgical treatment of a prostatocutaneous urinary fistula., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: Multiparametric magnetic resonance imaging guided prostate biopsy (mpMRI PBx) leads to a higher rate of successful nerve-sparing in robot-assisted laparoscopic prostatectomy (ns-RALP) for prostate cancer (PCa). This study aimed to evaluate the impact of mpMRI PBx compared to standard ultrasound-guided PBx on functional outcomes focusing on erectile function in patients following ns-RALP., Material and Methods: All RALPs performed between 01/2016 and 06/2021 were retrospectively stratified according to (attempted) ns vs. non ns RALPs and were then categorized based on the PBx technique (mpMRI PBx vs. standard PBx). We compared RALP outcomes such as pathological tumor stage, rates of secondary nerve resection (SNR) and positive surgical margin status (PSM). Furthermore, we explored the association between PBx-technique and patient-reported outcomes assessed 12 months after RALP using the prospectively collected 26-item Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. Chi-square tests and logistic regression analysis were conducted., Results: A total of 849 RALPs included 517 (61%) procedures with (attempted) ns. Among these, 37.5% were diagnosed via preoperative mpMRI PBx. Patients with a preoperative standard PBx had a 57% higher association of PSM ( p  = 0.030) compared to patients with mpMRI PBx and a 24% higher risk of erectile dysfunction (ED) 12 months post RALP ( p  = 0.025). When ns was attempted, we observed a significantly higher rate of SNR in patients who underwent a standard PBx compared to those who received a mpMRI PBx (50.8% vs. 26.7%, p  < 0.001) prior RALP. In comparison, upgrading occurred more often in the standard PBx group (50% vs. 40% mpMRI PBx, p  = 0.008)., Conclusion: The combination of mpMRI PBx for PCa diagnosis followed by ns-RALP resulted in significantly fewer cases of SNR, better oncological outcomes and reduced incidence of ED 1 year after surgery. This included fewer PSM and a lower rate of postoperative tumor upgrading., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Leitsmann, Uhlig, Bremmer, Mohr, Trojan, Leitsmann and Reichert.)

This case presents a 29-year-old man, with a urinary diversion via MAINZ Pouch I after cystectomy due to trauma in early childhood with a history of multiple previous surgeries. The reason for the presentation was a non-specific paraumbilical swelling on the right, which was disturbing for him. Despite further diagnostics by means of magnetic resonance imaging, a clear diagnosis of the subcutaneous tissue could not be made. After surgical removal of the complete cyst and after histological work-up, the diagnosis of an urachus-cyst could be made., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objective: To demonstrate the surgical influence of secondary resection on sexual function in finally unilateral nerve-sparing robot- assisted laparoscopic prostatectomies (RALPs) performed with the 'neurovascular structure-adjacent frozen-section examination' (NeuroSAFE) technique by prospectively collecting EPIC-26-questionnaires., Material & Methods: Sexual function status measured by the sexual-symptom-score (SexSS) in the EPIC-26-questionnaires was collected preoperatively and 12 months after RALP from 378 patients between 09/2019 and 04/2021. Cohorts of interest were defined as those patients undergoing unilateral nerve-sparing by secondary resection of the other neurovascular bundle (NVB), and as those patients undergoing primarily planned and successful unilateral nerve-sparing (unilateral nerve-sparing without secondary resection) in ≤cT2 prostate cancer. NeuroSAFE frozen section technique was performed in all nerve-sparing RALPs, and in case of cancer-positive surgical margins, the complete NVB was resected., Results: In 109 RALPs with unilateral nerve-sparing (48 primarily vs. 61 by secondary resection), analyses showed a significant difference in postoperative SexSS for 'unilateral nerve-sparing by secondary resection' compared with 'unilateral nerve-sparing without secondary resection' (43 [interquartile range (IQR): 14;50] vs. 26 [IQR: 22;62], P = 0.04). In multivariable analyses, the preoperative SexSS was predictive for postoperative erectile dysfunction (OR = 0.96, 95% confidence interval: 0.93-0.98, P < 0.001). Oncological safety was not compromised by secondary resection (prostate-specific antigen after 12 months 0.01 ng/mL vs. 0.01 ng/mL [P = 0.3] for unilateral nerve-sparing by secondary resection vs. unilateral nerve-sparing without secondary resection)., Conclusion: The results of this study suggest that nerve-sparing attempts applying the NeuroSAFEtechnique should be generously performed since a unilateral complete secondary resection leading to a unilateral nerve-sparing RALP did not seem to have a negative influence on sexual function and did not seem to compromise oncological safety compared with primarily performed and successful unilateral nerve-sparing RALP.

Purpose: The aim of this study was to assess the clinical feasibility of magnetic resonance imaging (MRI) T1 mapping using T1FLASH for assessment of prostate lesions., Methods: Participants with clinical suspicion for prostate cancer (PCa) were prospectively enrolled between October 2021 and April 2022 with multiparametric prostate MRI (mpMRI) acquired on a 3 T scanner. In addition, T1 mapping was accomplished using a single-shot T1FLASH technique with inversion recovery, radial undersampling, and iterative reconstruction. Regions of interest (ROIs) were manually placed on radiologically identified prostate lesions and representative reference regions of the transitional zone (TZ), benign prostate hyperplasia nodules, and peripheral zone (PZ). Mean T1 relaxation times and apparent diffusion coefficient (ADC) values (b = 50/b = 1400 s/mm 2 ) were measured for each ROI. Participants were included in the study if they underwent ultrasound/MRI fusion-guided prostate biopsy for radiologically or clinically suspected PCa. Histological evaluation of biopsy cores served as reference standard, with grading of PCa according to the International Society of Urological Pathology (ISUP). ISUP grades 2 and above were considered clinically significant PCa for the scope of this study. Histological results of prostate biopsy cores were anatomically mapped to corresponding mpMRI ROIs using biopsy plans. T1 relaxation times and ADC values were compared across prostate regions and ISUP groups. Across different strata, T1 relaxation time, ADC values, and diagnostic accuracy (area under the curve [AUC]) were compared using statistical methods accounting for clustered data., Results: Of 67 eligible participants, a total of 40 participants undergoing ultrasound/MRI fusion-guided prostate biopsy were included. Multislice T1 mapping was successfully performed in all participants at a median acquisition time of 2:10 minutes without evident image artifacts. A total of 71 prostate lesions was radiologically identified (TZ 49; PZ 22). Among those, 22 were histologically diagnosed with PCa (ISUP groups 1/2/3/4 in n = 3/15/3/1 cases, respectively). In the TZ, T1 relaxation time was statistically significantly lower for PCa compared with reference regions ( P = 0.029) and benign prostate hyperplasia nodules ( P < 0.001). Similarly, in the PZ, PCa demonstrated shorter T1 relaxation times versus reference regions ( P < 0.001). PCa also showed a trend toward shorter T1 relaxation times (median, 1.40 seconds) compared with radiologically suspicious lesions with benign histology (median, 1.47 seconds), although statistical significance was not reached ( P = 0.066). For discrimination of PCa from reference regions and benign prostate lesions, T1 relaxation times and ADC values demonstrated AUC = 0.80 and AUC = 0.83, respectively ( P = 0.519). Discriminating PCa from radiologically suspicious lesions with benign histology, T1 relaxation times and ADC values showed AUC = 0.69 and AUC = 0.62, respectively ( P = 0.446)., Conclusions: T1FLASH-based T1 mapping yields robust results for quantification of prostate T1 relaxation time at a short examination time of 2:10 minutes without evident image artifacts. Associated T1 relaxation times could aid in discrimination of significant and nonsignificant PCa. Further studies are warranted to confirm these results in a larger patient cohort, to assess the additional benefit of T1FLASH maps in conjunction with mpMRI sequences in the setting of deep learning, and to evaluate the robustness of T1FLASH maps compared with potentially artifact-prone diffusion-weighted imaging sequences., Competing Interests: Conflicts of interest and sources of funding: Francesco Giganti is a recipient of the 2020 Young Investigator Award (20YOUN15) funded by the Prostate Cancer Foundation/CRIS Cancer Foundation. Francesco Giganti reports consulting fees from Lucida Medical LTD outside of the submitted work. The authors have no further conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Multiple factors influence postprostatectomy incontinence (PPI). This study evaluates the association between an intraoperative urodynamic stress test (IST) with PPI., Materials and Methods: This is an observational, single-center, prospective evaluation of 109 robot-assisted laparoscopic radical prostatectomies (RALPs) performed between July 2020 and March 2021. All patients underwent an intraoperative urodynamic stress test (IST) in which the bladder is filled up to an intravesical pressure of 40 cm H 2 O to evaluate whether the rhabdomyosphincter is capable of withstanding the pressure and ensure continence. Early PPI was evaluated using a standardized 1-h pad test performed the day after removal of the urinary catheter. The association of IST and PPI was evaluated using univariate and multivariable logistic regression models., Results: Nearly 76.6% of the patients showed no urine loss during the IST ("sufficient" population group). There was no significant correlation between this group and PPI after catheter removal ( P = 0.5). Subgroup analyses of the "sufficient" patient population showed a 3.1 higher risk of PPI when no nerve sparing was performed (95% confidence interval: 1.05-9.70, P = 0.045)., Conclusion: A sufficient IST, as a surrogate variable for a fully obtained rhabdomyosphincter, has no significant predictive value on its own but seems to be the optimal prerequisite for continence, since the data shows that the lack of neurovascular supply required for a functioning sphincter leads up to a 3.1 times higher risk for PPI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright: © 2023 Urology Annals.)

Introduction: Growth arrest-specific protein 6 (Gas 6) is a ligand that plays a role in proliferation and migration of cells. For several tumor entities, high levels of Gas 6 are associated with poorer survival. We examined the prognostic role of Gas 6 in renal cell carcinoma (RCC), especially in papillary RCC (pRCC), which is still unclear., Methods: The patients' sample collection is a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of Gas 6 was determined by immunohistochemistry., Results: In total, Gas 6 staining was evaluable in 180 of 240 type 1 and 110 of 128 type 2 pRCC cases. Kaplan-Meier analysis disclosed no significant difference in 5-year overall survival for all pRCC nor either subtype. Also, Gas+ and Gas- groups did not significantly differ in any tumor or patient characteristics., Conclusion: Gas 6 was not found to be an independent prognostic marker in pRCC. Future studies are warranted to determine if Gas 6 plays a role as prognostic marker or therapeutic target in pRCC., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Elective scrotal surgery is associated with a high rate of postoperative complications. There is no specific recommendation for postoperative care., Aim: We investigated whether support underwear has an impact on postoperative complications and quality of life., Materials and Methods: From July 2020 to November 2021, patients with prior elective scrotal surgery were randomized into the intervention group "support underwear" or the control group. In addition to patient characteristics, intraoperative and postoperative findings were documented. The primary endpoint comprised postoperative complications. Secondary endpoints were prolonged length of hospital stay, emergency visits, unplanned readmissions, increased use of analgesics, and quality of life, which was recorded using the EQ5D (European Quality of Life 5 Dimensions) questionnaire preoperatively, on day 1 and 4 weeks postoperatively., Results: Data from 50 patients were analyzed. The mean age was 46.7 years (standard deviation [SD] 18.6). Inguinal surgery with/without orchiectomy (52%), hydrocele resection (22%), or ligation of varicocele (14%) were performed most frequently. The mean operating time was 62.8 min (SD 35.2); length hospital stay was 2.6 days (SD 1.2). In all, 20% of the patients suffered a postoperative complication. Type of surgery was significantly associated with postoperative complications (p = 0.01) and unplanned readmission (p = 0.04). Regarding biometric and perioperative data, there were no significant differences between the interventional group (n = 27) and control group (n = 23)., Conclusion: A nonnegligible number of complications occurs after elective scrotal surgery. Complications affects quality of life up to 4 weeks after the surgery. Postoperative care with support underwear does not appear to affect the postoperative complication rate, but it positively influences the quality of life in patients with scrotal access., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: To evaluate long-term continence rates (12 months) in patients after robot-assisted laparoscopic prostatectomy (RALP) in relation to their cognitive ability (CoAb), which proved to be a predictor for early post-prostatectomy incontinence., Material & Methods: This is the 12-month follow-up evaluation of our previously published observational single-center, prospective evaluation of 84 patients who underwent RALP as treatment of their localized prostate cancer between 07/2020 and 03/2021. Post-prostatectomy incontinence (PPI) was measured by asking patients about their 24 h pad usage, whereby 0 pads were considered continent and ≥1 pad was considered incontinent. CoAb was evaluated by performing the Mini-Mental State Examination prior to surgery. Possible predictors for PPI were evaluated using univariate and multivariable logistic regression models., Results: Multivariable logistic regression analyses identified early incontinence status and nerve sparing (NS) as independent predictors for PPI after 12 months, resulting in a 5.69 times higher risk for PPI when the loss of urine was between 10 and 50 ml during the early performed pad test (one day after catheter removal) compared to 0-1 ml loss of urine [95% confidence interval (CI): 1.33-28.30, p  = 0.024] and a 6.77 times higher risk for PPI, respectively, when only unilateral NS was performed compared to bilateral NS (95% CI: 1.79-30.89, p  = 0.007). CoAb lost its predictive value for long-term PPI ( p  = 0.44)., Conclusion: The results of this study suggest that PPI is a dynamic, rather than a static condition with a dynamically changing pathophysiology within the first 12 months after RALP. Coping methods and therapies should adapt to this circumstance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Reichert, Ploeger, Uhlig, Strauss, Henniges, Trojan and Mohr.)

Background: Nectin-4 contributes to tumor proliferation, lymphangiogenesis and angiogenesis in malignant tumors and is an emerging target in tumor therapy. In renal cell carcinoma (RCC) VEGF-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. Enfortumab vedotin-ejf (EV) is an antibody drug conjugate that targets Nectin-4. The aim of our study was to investigate the expression of Nectin-4 in a large cohort of papillary RCC specimens., Patients and Methods: Specimens were derived from the PANZAR consortium (Erlangen, Heidelberg, Herne, Homburg, Mainz, Mannheim, Marburg, Muenster, LMU Munich, TU Munich, and Regensburg). Clinical data and tissue samples from n = 190 and n = 107 patients with type 1 and 2 pRCC, respectively, were available. Expression of Nectin-4 was determined by immunohistochemistry (IHC)., Results: In total, Nectin-4 staining was moderately or strongly positive in of 92 (48.4%) of type 1 and 39 (36.4%) type 2 of pRCC cases. No associations between Nectin-4 expression and age at diagnosis, gender, grading, and TNM stage was found. 5 year overall survival rate was not statistically different in patients with Nectin-4 negative versus Nectin-4 positive tumors for the overall cohort and the pRCC type 2 subgroup, but higher in patient with Nectin-4 positive pRCC type 1 tumors compared to Nectin-4 negative tumors (81.3% vs. 67.8%, p = 0.042)., Conclusion: Nectin-4 could not be confirmed as a prognostic marker in pRCC in general. Due to its high abundance on pRCC specimens Nectin-4 is an interesting target for therapeutical approaches e.g. with EV. Clinical trials are warranted to elucidate its role in the pRCC treatment landscape., (© 2022. The Author(s).)

Background: The surgical management of benign prostatic obstruction (BPO) has greatly evolved in recent years., Objectives: The aim of this study is to present contemporary management and trends for surgical BPO therapy in Germany., Materials and Methods: Disease and procedure rates were extracted using the online platform reimbursement.INFO that is based on German hospital quality report data. For the diagnosis of benign prostate hyperplasia (BPH), the ICD codes N40 and D29.1 were used. For evaluation of the surgical procedures OPS codes 5‑600.0, 5‑601, 5‑603, 5‑609.4 and 5‑609.8 including their subcodes were used. In addition to descriptive analyses, trend and correlation analyses were performed., Results: In 2019, a total of 83,687 procedures for BPO in 473 urological departments were performed. The most common (71.7%) surgery was transurethral resection of the prostate (TUR-P). Holmium laser enucleation of the prostate (HoLEP; 9.5%) and surgical adenomectomy (5.6%) were the second and third most common procedures. Less often thulium laser enucleation (ThuLEP; 3.1%), laser vaporisation (2.9%) and electrical vaporisation (2.8%) were performed. All other techniques were performed in < 1%. Rates of HoLEP, ThuLEP and electrovaporisation have increased since 2006 (HoLEP: +42.42%/year, p < 0.001; ThuLEP: +20.6%/year, p = 0.99; electrovaporisation +43.42%/year, p < 0.001), while surgical adenomectomy decreased (-1.66%/year, p < 0.01). In 2019 mean length of hospital stay was 5.1 ± 0.1 days., Conclusions: TUR‑P remains the most often performed surgical treatment for BPO. Laser therapy-especially in centers-is increasing, while surgical adenomectomy continues to abate., (© 2022. The Author(s).)

Prostate specific membrane antigen (PSMA) is an emerging diagnostic and therapeutic target in prostate cancer. 68 Ga-PSMA-labeled hybrid imaging is used for the detection of prostate primary tumors and metastases. Therapeutic applications such as Lutetium-177 PSMA radionuclide therapy or bispecific antibodies that target PSMA are currently under investigation within clinical trials. The expression of PSMA, however, is not specific to prostate-tissue. It has been described in the neovascular endothelium of different types of cancer such as breast cancer, and clear cell renal cell carcinoma (ccRCC). The aim of this study was to analyze PSMA expression in papillary RCC (pRCC) type 1 and type 2, the most common non-ccRCC subtypes, and to evaluate the potential of PSMA-targeted imaging and treatment in pRCC. Formalin-fixed, paraffin-embedded tissue samples of primary tumors were analyzed for PSMA expression by immunohistochemistry. Out of n=374 pRCC specimens from the multicenter PANZAR consortium, n=197 pRCC type 1 and n=110 type 2 specimens were eligible for analysis and correlated with clinical data. In pRCC type 1 PSMA staining was positive in 4 of 197 (2.0%) samples whereas none (0/110) of the pRCC type 2 samples were positive for PSMA in this large cohort of pRCC patients. No significant PSMA expression was detected in pRCC. Reflecting current clinical evaluation of PMSA expression in RCC do not encourage further analysis in papillary subtypes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The aim of our study was to evaluate the impact of prostate biopsy technique (transrectal ultrasound (US)-prostate biopsy (PBx) versus multiparametric magnetic resonance imaging (mpMRI) targeted prostate biopsy (MRI-PBx) on intraoperative nerve-sparing and the rate of secondary neurovascular-bundle resection (SNR) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RARP). A real-time investigation with a frozen-section examination (NeuroSAFE) microscopically excluded or confirmed prostate cancer invasion of the nerve structures resulting in preservation of the neurovascular bundle or SNR. Additionally, we analyzed risk factors related to SNR, such as longer operation time and postoperative complications., Methods: The total study cohort was stratified according to non-nerve-sparing versus nerve-sparing RARP. Patients with nerve-sparing approach were then stratified according to biopsy technique (PBx vs. MRI-PBx). Further, we compared PBx versus MRI-PBx according to SNR rate., Results: We included a total of 470 consecutive patients, who underwent RARP for PCa at our institution between January 2016 and December 2019. Patients with a preoperative MRI-PBx had a 2.12-fold higher chance of successful nerve-sparing (without SNR) compared to patients with PBx (p < 0.01). Patients with preoperative MRI-PBx required 73% less intraoperative SNR compared to patients with PBx (p < 0.0001). Prior MRI-PBx is thus a predictor for successful nerve-sparing RARP approach., Conclusion: Preoperative MRI-PBx led to better oncological outcomes and less SNR. Young patients with good erectile function could benefit from a preoperative MRI-PBx before nerve-sparing RARP., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: Claudins are promising biomarkers for diagnosis and prognosis or targets for treatment. They play a major role in signal transduction and are important in nearly all aspects of tumorigenesis. Claudin 6 is a member of the claudin family and is part of the tight junction molecule. It is reactivated in several cancer types and serves as prognostic marker in, for example, gastric, breast or non small cell lung cancer. The prognostic role of Claudin 6 in renal cell carcinoma (RCC), especially in papillary RCC (pRCC), is still unclear., Patients and Methods: The patients' sample collection was a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of Claudin 6 was determined by immunohistochemistry., Results: In total, Claudin 6 staining was positive in 55 of 240 type 1 and 30 of 128 type 2 pRCC cases. Kaplan-Meier analysis disclosed an overall survival of 84% for Claudin 6- compared to 78% for Claudin 6 + in pRCC type 1 tumors (p = 0.449, log-rank) and 68% for Claudin 6- compared to 65.4% for Claudin 6 + in pRCC type 2 tumors (p = 0.364, log-rank)., Conclusion: In this study, claudin 6 expression showed no significant association regarding overall survival (OS) and therefore did not qualify as a prognostic marker in pRCC. Future studies will have to determine, whether Claudin 6 plays a prognostic role in other RCC entities. In addition, the function of Claudin 6 as a predictive marker for therapeutic approaches has to be evaluated in future studies., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

The tyrosine-protein kinase c-Met plays a decisive role in numerous cellular processes, as a proto-oncogene that supports aggressive tumor behavior. It is still unknown whether c-Met could be relevant for prognosis of papillary RCC (pRCC). Specimen collection was a collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from 197 and 110 patients with type 1 and 2 pRCC, respectively. Expression of cMET was determined by immunohistochemistry. In total, cMET staining was evaluable in of 97 of 197 type 1 and 63 of 110 type 2 pRCC cases. Five-year overall survival revealed no significant difference in dependence of cMET positivity (cMET - vs. cMET + : pRCC type 1: 84.8% vs. 80.3%, respectively [p = 0.303, log-rank]; type 2: 71.4% vs. 64.4%, respectively [p = 0.239, log-rank]). Interestingly, the subgroup analyses showed a significant difference for cMET expression in T stage and metastases of the pRCC type 2 (p = 0.014, p = 0.022, chi-square). The cMET-positive type 2 collective developed more metastases than the cMET-negative cohort (pRCC type 2 M+: cMET -: 2 [4.3%] vs. cMET + : 12 [19%]). cMET expression did not qualify as a prognostic marker in pRCC for overall survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Urinary incontinence (UI) is a wide-spread and feared side-effect of conventional or even robot-assisted laparoscopic prostatectomy (RALP) due to its high impact on patients' quality of life (QoL). Non-modifiable risk factors for UI have already been identified - on surgical and patient side. Yet, to our knowledge, focus thus far has not been placed on functional aspects regarding general cognitive ability. Materials and Methods: This is an observational single-center, prospective, double-blinded evaluation of 109 RALPs performed between 07/2020 and 03/2021. All patients underwent a Mini Mental State Examination (MMSE) prior to surgery to evaluate their cognitive ability. Early post-prostatectomy incontinence (PPI) was evaluated using a standardized 1 h pad test performed 24 h after removal of the urinary catheter. The association between MMSE results and PPI were evaluated using univariate and multivariate logistic regression models. Results: Multivariate logistic regression analyses identified MMSE results and nerve sparing (NS) as independent predictors for PPI in patients with an intermediate MMSE result (25-27 points) having a 3.17 times higher risk of PPI when compared to patients with a good MMSE result (≥28) (95% Confidence Interval (CI): 1.22-9.06, p = 0.023), while patients without NS had a 3.53 times higher risk of PPI when compared to patients with NS (95% CI: 1.54-11.09, p = 0.006). Conclusion: A lower cognitive ability should be treated as a non-modifiable risk-factor for early PPI. In the future it could find its place as a clinical screening tool to identify patients who require more attention especially in the pre-, but also in the postoperative phase., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Reichert, Popeneciu, Uhlig, Trojan and Mohr.)

Introduction: Programmed death-1 ligand (PD-L1) has been often studied in different types of renal-cell carcinoma (RCC). For example, in clear-cell renal carcinoma it is well established that programmed death-1 receptor and PD-L1 are important prognostic markers. In contrast, the role of programmed death-2 ligand (PD-L2) as prognostic marker remains unclear. The aim of this study was to evaluate if PD-L2 expression could play a role as a prognostic marker for papillary RCC (pRCC)., Methods: The patients' sample collection was a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of PD-L2 was determined by immunohistochemistry. In total, PD-L2 staining was evaluable in 185 of 240 type 1 and 99 of 128 type 2 pRCC cases., Results: PD-L2 staining was positive in 67 (36.2%) of type 1 and in 31 (31.3%) of type 2 pRCC specimens. The prevalence of PD-L2+ cells was significantly higher in high-grade type 1 tumors (p = 0.019) and in type 2 patients with metastasis (p = 0.002). Kaplan-Meier analysis disclosed significant differences in 5-year overall survival (OS) for patients with PD-L2- compared to PD-L2+ in pRCC type 1 of 88.4% compared to 73.6% (p = 0.039) and type 2 of 78.8% compared to 39.1% % (p < 0.001). However, multivariate analysis did not identify the presence of PD-L2+ cells neither in type 1 nor type 2 pRCC as an independent predictor of poor OS., Discussion/conclusion: PD-L2 expression did not qualify as an independent prognostic marker in pRCC. Future studies will have to determine whether anti-PD-L2-targeted treatment may play a role in pRCC and expression can potentially serve as a predictive marker for these therapeutic approaches., (© 2022 S. Karger AG, Basel.)

Background: In metastatic clear cell renal cell carcinoma (ccRCC), different combination therapies, each including anti-PD-1 immune checkpoint blockade (ICB), are applied as first-line treatment. Robust predictive biomarkers for rational upfront therapy decisions are lacking, although they are urgently needed. Recently, we showed that CTLA4 promoter methylation predicts response to ICB in melanoma. Here, we aimed to investigate CTLA4 methylation in ccRCC and its utility to serve as a predictive biomarker for anti-PD-1 based ICB in metastatic ccRCC., Methods: CTLA4 methylation was analyzed with regard to transcriptional gene activity (mRNA expression), intratumoral immune cell composition, and clinical course in two ccRCC cohorts obtained from The Cancer Genome Atlas (TCGA cohort, n=533) and the University Hospital Bonn (UHB Non-ICB Cohort, n=116). In addition, CTLA4 methylation as well as CD8 + T cell infiltrates and PD-L1 expression were evaluated in pre-treatment samples from a multicenter cohort (RCC-ICB Cohort, n=71). Patients included in the RCC-ICB Cohort were treated with either first line anti-PD-1 based combination therapy (n=25) or monotherapy post-tyrosine kinase inhibition in second line or later. Analyses were performed with regard to treatment response according to RECIST, progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) following treatment initiation., Results: CTLA4 promoter hypomethylation was significantly correlated with CTLA4 mRNA expression, lymphocyte infiltration, and poor OS in both primary ccRCC cohorts (TCGA: HR 0.30 (95% CI 0.18 to 0.49), p<0.001; UHB Non-ICB: HR 0.35 (95% CI 0.16 to 0.75), p=0.007). In contrast, CTLA4 promoter hypomethylation predicted response and, accordingly, favorable outcomes (PFS and OS) in patients with ICB-treated ccRCC, overcompensating the negative prognostic value of CTLA4 hypomethylation at initial diagnosis. Moreover, in multivariable Cox regression, CTLA4 promoter hypomethylation remained an independent predictor of improved outcome in ICB-treated ccRCC after co-adjustment of the International Metastatic Renal Cell Carcinoma Database Consortium score (HR 3.00 (95% CI 1.47 to 6.28), p=0.003)., Conclusions: Our study suggests CTLA4 methylation as a powerful predictive biomarker for immunotherapy response in metastatic RCC., Competing Interests: Competing interests: DD owns patents and patent applications on biomarker technologies and methylation of immune checkpoint genes as predictive and prognostic biomarkers (DE 10 2016 005 947.8, DE 10 2015 009 187.5, DE 10 2017 125 780.2, PCT/EP2016/001237). The patents are licensed to Qiagen GmbH (Hilden, Germany). DD is a consultant of Qiagen. The University Hospital Bonn (PI DD) received research funding from Qiagen., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

To reduce noise pollution and consequently stress during robot-assisted laparoscopic radical prostatectomy (RALP) the aim of our study was to evaluate the silent operation theatre optimisation system (SOTOS) in its effectiveness. In the operating room (OR) the noise level is between 80 and 85 decibel (dB). Noise corresponds to a major stress factor for surgical teams and especially surgeons. The use of the da Vinci surgical system entails an additional aspect of noise in the OR. The SOTOS surgical team used wired or wireless headphone/microphone combinations to communicate. We measured sound pressure levels in two different locations in the OR and the heart rate of every surgical team member as an indicator of the stress level. We further captured subjective acceptance of SOTOS as well as perioperative data such as surgical time. We prospectively randomised 32 RALP patients into two study arms. Sixteen surgeries were performed using SOTOS and 16 without (control). Overall, the mean sound pressure level in the SOTOS group was 3.6 dB lower compared to the control (p < 0.001). The highest sound pressure level measured was 96 dB in the control group. Mean heart rates were 81.3 beats/min for surgeons and 90.8 beats/min for circulating nurses. SOTOS had no statistically significant effect on mean heart rates of the operating team. Subjective acceptance of SOTO was high. Our prospective evaluation of SOTOS in RALP could show a significant noise reduction in the OR and a high acceptance by the surgical stuff., (© 2020. Springer-Verlag London Ltd., part of Springer Nature.)

Purpose: Several studies have demonstrated an advantage of 68 Ga-PSMA-PET/CT as staging modality for detection of prostate cancer (PCa) metastases. Data concerning metastatic manifestation and impact on PCa development of mesorectal lymph nodes (MLN) is limited. Our investigation describes MLN metastases as index lesion in 68 Ga-PSMA PET/CT imaging for recurrent PCa. Methods: Twelve PCa patients with biochemical recurrence (BCR) after primary therapy who prospectively underwent a baseline 68 Ga-PSMA-PET/CT initially showed MLN metastases. Eight of these patients received a follow-up 68 Ga-PSMA-PET/CT to evaluate treatment response and further evolution. Prostate-specific antigen (PSA)-levels, changes in PSMA-uptake of MLN metastases and further 68 Ga-PSMA PET/CT findings were recorded. Results: Median PSA at the first 68 Ga-PSMA-PET/CT was 5.39 ng/ml. In all patients therapeutic management changed after the first 68 Ga-PSMA-PET/CT. Androgen deprivation therapy (ADT) was initiated in seven of eight patients, one patient restarted initial ADT. Three patients additionally received salvage radiation therapy (sRT) including the prostatic lodge and docetaxel chemotherapy was started in one case. At follow-up, a decrease of PSA-level was detected in all patients (median 2.05 ng/ml) after median 10 months. In six of eight patients we observed a decrease or complete regress of PSMA-uptake in MLN in the follow-up 68 Ga-PSMA-PET/CT. Conclusion: MLN metastases detected by 68 Ga-PSMA-PET/CT seem to be a relevant localization of tumor manifestation and may serve as index lesion in the treatment of recurrent PCa. Besides the known oncological benefits of ADT and sRT, in case of sole MLN metastases individualized therapy like salvage lymphadenectomy or RT with a defined radiation field could be options for these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Leitsmann, Schmid, Sahlmann, Trojan and Strauss.)

Background: Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) play a decisive role as prognostic markers in clear-cell renal cell carcinoma (RCC). To date, the role of PD-1/PD-L1 as a prognostic marker in papillary RCC (pRCC) remains scarce., Patients and Methods: Patients' sample collection was a joint collaboration of the nationwide PANZAR consortium - a multicenter study. Medical history and tumor specimens were collected from 245 and 129 patients with pRCC types 1 and 2, respectively. Expression of PD-1 and PD-L1 was determined by immunohistochemistry in pRCC and tumor-infiltrating mononuclear cells., Results: Of 374 pRCC specimens, 204 type 1 and 97 type 2 were evaluable for PD-1 and PD-L1 expression analysis. In total, PD-1 and PD-L1 expression were found in 8 (4.9%) of 162 and 12 (7.2%) of 166 evaluable pRCC type 1 specimens. Comparably, PD-1 and PD-L1 expression were found in 2 (2.4%) of 83 and 5 (6.2%) of 81 evaluable pRCC type 2 specimens. Hardly any clinically relevant associations between PD-1 and PD-L1 positivity and clinicopathologic or clinical courses were observed, neither in pRCC type 1 nor type 2., Conclusion: The analysis of a large pRCC cohort from a multicenter consortium revealed no impact of PD-1/PD-L1 expression on prognosis in patients with pRCC with predominantly limited disease status, neither for type 1 nor type 2. However, the impact of PD-1 and PD-L1 in more advanced pRCC disease needs further elucidation., (Copyright © 2020. Published by Elsevier Inc.)

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand-foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand-foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

Objective: To compare the incidence of postoperative flank bulges between patients with multiple-layer closure and single superficial-layer closure after retroperitoneal surgery via open flank incision in the SIngle versus MUltiple-LAyer wound Closure for flank incision (SIMULAC) trial., Patients and Methods: The study was a randomised controlled, patient- and assessor-blinded, multicentre trial. Between May 2015 and February 2017, 225 patients undergoing flank incisions were randomised 1:1 to a multiple-layer closure (SIMULAC-I) or a single superficial-layer closure (SIMULAC-II) group. The primary outcome was the occurrence of a flank bulge 6 months after surgery., Results: Overall, 177 patients (90 in SIMULAC-I, 87 in SIMULAC-II) were eligible for final assessment. The cumulative incidence of a flank bulge was significantly higher in the SIMULAC-II group (51.7%) compared to the SIMULAC-I group [34.4%; odds ratio (OR) 2.04, 95% confidence interval (CI) 1.11-3.73; P = 0.02]. Rate of severe postoperative complications (4.4% SIMULAC-I vs 10.3% SIMULAC-II; P = 0.21) or hernia (6.7% SIMULAC-I vs 10.3% SIMULAC-II; P = 0.59) was similar between the groups. There was no difference in pain (visual analogue scale) and the requirement for pain medication at 6 months postoperatively. Quality of life assessed with the European Quality of Life 5 Dimensions Questionnaire was higher in the SIMULAC-I group compared to the SIMULAC-II group at 6 months postoperatively, with a (median range) score of 80 (30-100) vs 75 (5-100) (P = 0.012)., Conclusion: The overall risk of a flank bulge after flank incision is high. Multiple-layer closure after flank incision should be performed as a standard procedure., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Focal therapies such as high-intensity focused ultrasound (HiFU) are an emerging therapeutic option for prostate cancer (PCA). Thermal or mechanical effects mediate most therapies. Moreover, locally administered drugs such as bicalutamide or docetaxel are new focal therapeutic options. We assessed the impact of such focal medical treatments on cell viability and heat sensitivity by pre-treating PCA cell lines and then gradually exposing them to heat. The individual heat response of the cell lines tested differed largely. Vertebral-Cancer of the Prostate (VCaP) cells showed an increase in metabolic activity at 40-50 °C. Androgen receptor (AR)-negative PC3 cells showed an increase at 51.3 °C and were overall more resistant to higher temperatures. Pre-treatment of VCaP cells with testosterone (VCaPrev) leads to a more PC3-like kinetic of the heat response. Pre-treatment with finasteride and bicalutamide did not cause changes in heat sensitivity in any cell line. Mitoxantrone treatment, however, shifted heat-induced proliferation loss to lower temperature in VCaP cells. Further analysis via RNAseq identified a possible correlation of heat resistance with H3K27me3-dependent gene regulation, which could be related to an increase in the histone methyltransferase EZH2 and a possible neuroendocrine differentiation. Pre-treatment with mitoxantrone might be a perspective for HiFU treatment. Further studies are needed to evaluate possible combinations with Hsp90 or EZH2 inhibitors.

This study evaluates the diagnostic performance of radiomic features and machine learning algorithms for renal tumor subtype assessment in venous computed tomography (CT) studies from clinical routine. Patients undergoing surgical resection and histopathological assessment of renal tumors at a tertiary referral center between 2012 and 2019 were included. Preoperative venous-phase CTs from multiple referring imaging centers were segmented, and standardized radiomic features extracted. After preprocessing, class imbalance handling, and feature selection, machine learning algorithms were used to predict renal tumor subtypes using 10-fold cross validation, assessed as multiclass area under the curve (AUC). In total, n = 201 patients were included (73.7% male; mean age 66 ± 11 years), with n = 131 clear cell renal cell carcinomas (ccRCC), n = 29 papillary RCC, n = 11 chromophobe RCC, n = 16 oncocytomas, and n = 14 angiomyolipomas (AML). An extreme gradient boosting algorithm demonstrated the highest accuracy (multiclass area under the curve (AUC) = 0.72). The worst discrimination was evident for oncocytomas vs. AML and oncocytomas vs. chromophobe RCC (AUC = 0.55 and AUC = 0.45, respectively). In sensitivity analyses excluding oncocytomas, a random forest algorithm showed the highest accuracy, with multiclass AUC = 0.78. Radiomic feature analyses from venous-phase CT acquired in clinical practice with subsequent machine learning can discriminate renal tumor subtypes with moderate accuracy. The classification of oncocytomas seems to be the most complex with the lowest accuracy.

The aim of this study was to discriminate malignant and benign clinical T1 renal masses on routinely acquired computed tomography (CT) images using radiomics and machine learning techniques.Adult patients undergoing surgical resection and histopathological analysis of clinical T1 renal masses were included. Preoperative CT studies in venous phase from multiple referring centers were included, without restriction to specific CT scanners, slice thickness, or degrees of artifacts. Renal masses were segmented and 120 standardized radiomic features extracted. Machine learning algorithms were used to predict malignancy of renal masses using radiomics features and cross-validation. Diagnostic accuracy of machine learning models and assessment by independent blinded radiologists were compared based on the gold standard of histopathologic diagnosis.A total of 94 patients met inclusion criteria (benign renal masses: n = 18; malignant: n = 76). CT studies from 18 different scanners were assessed with median slice thickness of 2.5 mm and artifacts in 15 cases (15.9%).Area under the receiver-operating-characteristics curve (AUC) of random forest (random forest [RF], AUC = 0.83) was significantly higher compared to the radiologists (AUC = 0.68, P = .047). Sensitivity was significantly higher for RF versus radiologists (0.88 vs 0.80, P = .045), whereas specificity was numerically higher for RF (0.67 vs 0.50, P = .083).Although limited by an overall small sample size and few benign renal tumors, a radiomic features and machine learning approach suggests a high diagnostic accuracy for discrimination of malignant and benign clinical T1 renal masses on venous phase CT. The presented algorithm robustly outperforms human readers in a real-life scenario with nonstandardized imaging studies from various referring centers.

Purpose: To assess use of stereotactic body radiotherapy (SBRT) for stage I renal cell carcinoma (RCC) and compare outcomes with thermal ablation and partial nephrectomy (PN)., Materials and Methods: The 2004-2015 National Cancer Database was investigated for histopathologically proven stage I RCC treated with PN, cryoablation, radiofrequency (RF) or microwave (MW) ablation, or SBRT. Patients were propensity score-matched to account for potential confounders, including patient age, sex, race, comorbidities, tumor size, histology, grade, tumor sequence, administration of systemic therapy, treatment in academic vs nonacademic centers, treatment location, and year of diagnosis. Overall survival (OS) was evaluated with Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models., Results: A total of 91,965 patients were identified (SBRT, n = 174; PN, n = 82,913; cryoablation, n = 5,446; RF/MW ablation, n = 3,432). Stage I patients who received SBRT tended to be older women with few comorbidities treated at nonacademic centers in New England states. After propensity score matching, a cohort of 636 patients was obtained with well-balanced confounders between treatment groups. In the matched cohort, OS after SBRT was inferior to OS after PN and thermal ablation (PN vs SBRT, hazard ratio [HR] = 0.29, 95% confidence interval [CI] 0.19-0.46, P < .001; cryoablation vs SBRT, HR = 0.40, 95% CI 0.26-0.60, P < .001; RF/MW ablation vs SBRT, HR = 0.46, 95% CI 0.31-0.67, P < .001). Compared with PN, neither cryoablation nor RF/MW ablation showed significant difference in OS (cryoablation vs PN, HR = 1.35, 95% CI 0.80-2.28, P = .258; RF/MW ablation vs PN, HR = 0.64, 95% CI 0.95-2.55, P = .079)., Conclusions: Current SBRT protocols show lower OS compared with thermal ablation and PN, whereas thermal ablation and PN demonstrate comparable outcomes., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Offering a full-day program including practical courses and the possibility of direct exchange between medical students and university teachers, the "Göttinger Aufschneidertag" was launched to generate enthusiasm for surgery. Workshops comprising four surgical disciplines enable participants to gain insight into the craft of surgery. The program aims to create interest in surgery among medical students at an early point of their studies and to make them enjoy their profession., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Alzheimer's disease (AD) pathology precedes the onset of clinical symptoms by several decades. Thus, biomarkers are required to identify prodromal disease stages to allow for the early and effective treatment. The methoxy-X04-derivative BSC4090 is a fluorescent ligand which was designed to target neurofibrillary tangles in AD. BSC4090 staining was previously detected in post-mortem brains and olfactory mucosa derived from AD patients. We tested BSC4090 as a potential diagnostic marker of prodromal and early AD using olfactory mucosa biopsies from 12 individuals with AD, 13 with mild cognitive impairment (MCI), and 10 cognitively normal (CN) controls. Receiver-operating curve analysis revealed areas under the curve of 0.78 for AD versus CN and of 0.86 for MCI due to AD versus MCI of other causes. BSC4090 labeling correlated significantly with cerebrospinal fluid levels of tau protein phosphorylated at T181. Using NMR spectroscopy, we find that BSC4090 binds to fibrillar and pre-fibrillar but not to monomeric tau. Thus, BSC4090 may be an interesting candidate to detect AD at the early disease stages.

Background: Multiple surgical treatment options are available for the treatment of ureteropelvic junction obstruction (UPJO). The aim of this study is to compare the most frequently used technics in a comprehensive network approach., Methods: A systematic literature search of the EMBASE, MEDLINE and COCHRANE libraries was conducted in January 2018. Publications were included that evaluated at least two of the following surgical techniques: open pyeloplasty (OP), endopyelotomy (EP), laparoscopic (LP) and robot assisted pyeloplasty (RP). Main outcomes were operative success, complications, urinary leakage, re-operation, transfusion rate, operating time, and length of stay. Network meta-analyses with random effects models simultaneously assessed effectiveness of all surgical techniques., Results: A total of 26 studies including 3143 patients were analyzed. Compared with RP, EP and LP showed lower operative success rates (EP: OR = 0.09, 95%CI:0.05-0.19; p < 0.001; LP: OR = 0.51, 95%CI:0.31-0.84; p = 0.008). Compared with OP, LP and RP had lower risk for complications (LP: OR = 0.62; 95%CI:0.41-0.95; p = 0.027; RP: OR = 0.41; 95%CI:0.22-0.79; p = 0.007). Compared with RP, no significant differences were detected for urinary leakage or re-operation, transfusion rates. Compared with EP, RP yielded longer operating time (mean = 102.87 min, 95%CI:41.79 min-163.95 min, p = < 0.001). Further significant differences in operating times were detected when comparing LP to EP (mean = 115.13 min, 95%CI:65.63 min-164.63 min, p = < 0.001) and OP to EP (mean = 91.96 min, 95%CI:32.33 min-151.58 min, p = 0.003)., Conclusions: Multiple surgical techniques are available for treatment of UPJO. RP has the highest rates of operative success and as well as LP lower complication rates than OP. Although surgical outcomes are worse for EP, its operating time is shorter than OP, RP, and LP. Surgeons should consider these findings when selecting the optimal treatment method for individual patients.

Aims: In recent years, the human brain-bladder control network has been visualized in different functional magnetic resonance imaging (fMRI) studies. The role of the brainstem and suprapontine regions has been elucidated. Especially the pontine region and the periaqueductal gray, as the central structures of the micturition circuit, were demonstrated. Detrusor sphincter dyssynergia (DSD) is a common problem in patients with neurological diseases. Residual urine and consecutive urinary tract infections with the risk of kidney damage remain a problem. In the present study, we used fMRI of the brain to compare the activation sites of patients with DSD with those of our previously published healthy controls with special emphasis on the brainstem region., Methods: fMRI was performed in 11 patients with DSD who had an urge to void due to a filled bladder. In a nonvoiding model, they were instructed to contract or to relax the pelvic floor muscles repetitively., Results: In patients with DSD, we could reproduce the activation sites found in healthy subjects, showing the regions in the brainstem as well as the other micturition-related areas. The activation of the pontine region was more rostral/dorsal compared with the healthy volunteers., Conclusion: Interestingly, we detected the well-known activation in the pontine region in the patients in the dorsal/rostral part compared with the more ventral activation in the healthy volunteers, suggesting that the L-region of the pontine micturition center is more prominent in cases of DSD., (© 2019 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.)

Purpose: 68Ga-PSMA PET/CT imaging is a promising modality for the staging of recurrent prostate cancer (PCa). Current evidence suggests limited diagnostic value of the 68Ga-PSMA PET/CT in PSA-levels ≤0.3ng/mL. Experimental data have demonstrated na increase in PSMA-expression in PCa metastases by androgen deprivation in vitro. The aim of the current study was to investigate a possible enhancing effect of PSMA with low-dose androgen deprivation in patients with BCR and low PSA-levels., Materials and Methods: Five patients with PCa and BCR, following radical prostatectomy, underwent 68Ga-PSMA PET/CT. A consecutive 68Ga-PSMA PET/CT was performed 6 to 11 days after injection of 80mg of Degarelix (Firmagon®). We recorded PSA and testosterone serum-levels and changes of PSMA-uptake in 68Ga-PSMA PET/CT images., Results: Median PSA prior 68Ga-PSMA PET/CT was 0.27ng/mL. All patients had a decrease in testosterone serum levels from median 2.95μg/l to 0.16μg/l following Degarelix injection. We observed an increase in the standardized uptake value (SUV) in PSMA-positive lymphogenous and osseous lesions in two patients following androgen deprivation. In another two patients, no PSMA positive signals were detected in either the fi rst or the second scan., Conclusion: Our preliminary results of this feasibility assessment indicate a possible enhancing effect of PSMA-imaging induced by low-dose ADT. Despite several limitations and the small number of patients, this could be a new approach to improve staging by 68Ga-PSMA PET/CT in PCa patients with BCR after primary therapy. Further prospective studies with larger number of patients are needed to validate our findings., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

To assess whether left and right-sided renal cell carcinoma (RCC) carry side-specific outcomes.Surgically treated RCC patients were included from the United States Surveillance, Epidemiology and End Results database (Surveillance, Epidemiology and End Results database [SEER]; 2013 version) and the German Centre for Cancer Registry Data (ZfKD; 2000-2014). Bilateral RCC, those with missing RCC staging, follow-up time, and survival status were excluded. Cancer-specific survival (CSS) according to RCC side was compared using multivariable Cox regression.Seventeen thousand seven hundred nine SEER patients and 41,967 ZfKD patients were included. In both datasets, patients with left-sided RCC had higher T status and more often presented with nodal positive or metastatic disease. In the SEER dataset 1258 (14.33%) patients with left-sided RCC underwent lymphadenectomy (LAD), compared to 908 (10.17%) LADs in right-sided RCC (P <.001). CSS was inferior for left-sided in both datasets after multivariable adjustment (SEER HR = 1.187, 95% CI 1.048-1.345, P = .007, P = .008; ZfKD HR = 1.155, 95% CI 1.046-1.275, P = .004).In the SEER population, site-specific CSS differences were driven by whether or not a LAD was performed. Among SEER patients with LAD no statistically significant differences in laterality were observed (HR 1.096, 95% CI 0.8977-1.337, P = .396) whereas, in absence of LAD, CSS was shorter for individuals with left-sided tumor (HR = 1.176, 95%CI 1.002-1.38, P = .0468).Although the overall survival difference was only marginal, left-sided RCC in surgically treated patients tends to present at more advanced stage and has in general worse CSS, especially in patients without LAD. Site-specific lymphogenic spread patterns might contribute to these findings. Further prospective studies should evaluate, whether side-adapted LAD protocols influence outcomes in RCC patients.

Purpose: To compare partial nephrectomy (PN), radiofrequency ablation (RFA), cryoablation (CRA) and microwave ablation (MWA) regarding oncologic, perioperative and functional outcomes., Material and Methods: The MEDLINE, EMBASE and COCHRANE libraries were searched for studies comparing PN, RFA, CRA or MWA and reporting on any-cause or cancer-specific mortality, local recurrence, complications or renal function. Network meta-analyses were performed., Results: Forty-seven studies with 24,077 patients were included. Patients receiving RFA, CRA or MWA were older and had more comorbidities compared with PN. All-cause mortality was higher for CRA and RFA compared with PN (incidence rate ratio IRR = 2.58, IRR = 2.58, p < 0.001, respectively). No significant differences in cancer-specific mortality were evident. Local recurrence was higher for CRA, RFA and MWA compared with PN (IRR = 4.13, IRR = 1.79, IRR = 2.52, p < 0.05 respectively). A decline in renal function was less pronounced after RFA versus PN, CRA and MWA (mean difference in GFR MD = 6.49; MD = 5.82; MD = 10.89, p < 0.05 respectively)., Conclusion: Higher overall survival and local control of PN compared with ablative therapies did not translate into significantly better cancer-specific mortality. Most studies carried a high risk of bias by selecting younger and healthier patients for PN, which may drive superior survival and local control. Physicians should be aware of the lack of high-quality evidence and the potential benefits of ablative techniques for certain patients, including a superior complication profile and renal function preservation., Key Points: • Patients selected for ablation of small renal masses are older and have more comorbidities compared with those undergoing partial nephrectomy. • Partial nephrectomy yields lower all-cause mortality, which is probably biased by patient selection and does not translate into prolonged cancer-free survival. • The decline of renal function is smallest after radiofrequency ablation for small renal masses.

Papillary renal cell carcinoma (PRCC) is currently divided in 2 subtypes. We reviewed a large cohort of PRCC and correlated subtype, morphological features and diagnostic marker expression with overall survival (OS) to uncover differences between the 2 subtypes. Three hundred seventy-six renal tumors initially diagnosed as PRCC with clinical and survival data were collected from the participating centers. Two hundred forty-six tumors were classified as PRCC1 (65.4%) and 130 as PRCC2 (34.6%) and graded according to the 2016 World Health Organization/International Society of Urological Pathology grading system. Morphological features (abundant cytoplasm, necrosis, fibrous stroma, foamy macrophages and psammoma bodies) were noted. Immunohistochemical stains (MIB1, p53, Racemase, EMA, CK7, CK20, E-Cadherin) were performed using tissue microarrays. χ 2 -Tests, log-rank tests and uni- and multivariate Cox regression analysis were performed. Both subtypes displayed different morphological features and immunohistochemical profiles: abundant cytoplasm was more frequent in PRCC2, while foamy macrophages were more common in PRCC1. Abundant cytoplasm and presence of psammoma bodies were associated with poorer OS. PRCC1 showed more frequent CK7 expression, PRCC2 more frequent E-Cadherin, p53 and higher MIB1 expression (>15%). Expression of Racemase and CK7 was associated with better OS, while high MIB1 (>15%) was associated with poorer OS. In multivariate analysis, the only independent predictors of OS were proliferation (MIB1), tumor stage, metastasis and age at surgery. Subtype was not an independent prognostic factor. Therefore, PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Context: The incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non-muscle-invasive UCB., Objective: To conduct a meta-analysis evaluating gender-specific differences in recurrence of non-muscle-invasive urinary bladder cancer (NMIBC)., Evidence Acquisition: An unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggeŕs test., Evidence Synthesis: Of 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01-1.23, p=0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13-2.39, p=0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32-2.15, p<0.001). Sensitivity analyses confirmed female patients at increased risk for UCB recurrence., Conclusions: Women are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses., Patient Summary: In this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We summarize the evidence on gender specific differences in disease-free, cancer specific and overall survival after radical cystectomy for bladder cancer., Materials and Methods: We performed a systematic literature search of MEDLINE®, Embase® and the Cochrane Library in July 2017. Studies evaluating gender specific differences in disease-free, cancer specific or overall survival after radical cystectomy for bladder cancer were included in study. Analyses included random effect meta-analysis, subgroup analyses, meta-influence and cumulative meta-analyses. Funnel plots and the Egger test were used to assess publication bias., Results: Of the 3,868 studies identified during the literature search 59 published between 1998 and 2017 were included in analysis. Of the studies 30 in a total of 38,321 patients evaluated disease-free survival, 44 in a total of 69,666 evaluated cancer specific survival and 26 in a total of 30,039 evaluated overall survival. Random effect meta-analyses revealed decreased disease-free, cancer specific survival and overall survival in female patients than in their male counterparts. Pooled estimates showed a HR of 1.16 (95% CI 1.06-1.27, p = 0.0018) for disease-free survival, 1.23 (95% CI 1.15-1.31, p <0.001) for cancer specific survival and 1.08 (95% CI 1.03-1.12, p = 0.0004) for overall survival. Subgroup analyses confirmed impaired disease-free, cancer specific and overall survival in female patients in all strata. Publication bias was evident only for studies of cancer specific survival (Egger test p = 0.0029). After adjusting for publication bias by the trim and fill method the corrected pooled estimated HR of cancer specific survival was 1.13 (95% CI 1.05-1.21, p = 0.0012)., Conclusions: Female patients who underwent radical cystectomy for bladder cancer demonstrated worse disease-free, cancer specific and overall survival than their male counterparts. The multifactorial etiology might include epidemiological differences, gender specific health care discrepancies and hormonal influences., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Deregulation of the insulin-like growth factor (IGF) axis and dysbalance of components of the IGF system as potential therapeutic targets have been described in different tumor types. IGF2 is a major embryonic growth factor and an important activator of IGF signaling. It is regulated by imprinting in a development- and tissue-dependent manner and has been implicated in a broad range of malignancies including prostate cancer (PCa). Loss of imprinting (LOI) usually results in bi-allelic gene expression and increased levels of IGF2. However, the regulatory mechanisms and the pathophysiological impact of altered IGF2 expression in PCa remain elusive. Here, we show that in contrast to many other tumors, IGF2 mRNA and protein levels were decreased in 80% of PCa in comparison with non-neoplastic adjacent prostate and were independent of LOI status. Instead, IGF2 expression in both tumors and adjacent prostate depended on preferential usage of the IGF2 promoters P3 and P4. Decreased IGF2 expression in tumors was strongly related to hypermethylation of these two promoters. Methylation of the A region in promoter P4 correlated specifically with IGF2 expression in the 20% of PCa where IGF2 was higher in tumors than in adjacent prostate. We conclude that IGF2 is downregulated in most PCa and may be particularly relevant during early stages of tumor development or during chemotherapy and androgen deprivation. PCa differs from other tumors in that IGF2 expression is mainly regulated through methylation of promoter-specific and not by imprinting. Targeting of promoter-specific regions may have relevance for the adjuvant treatment of PCa., (© 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Purpose: To evaluate survival of patients with localized T1a clear cell renal cell carcinoma (ccRCC) who received cryosurgery or thermal ablation compared to deferred therapy., Materials and Methods: We included 733 patients with histopathologically confirmed localized T1a ccRCC who either received cryosurgery (n = 315) or thermal ablation (n = 155), as well as patients who deferred therapy (n = 263) from the 2000-2013 Surveillance, Epidemiology, and End Results Program urinary cancer file. Cox proportional hazard models were used to compare cancer-specific survival (CSS) across subgroups. Sensitivity analyses were conducted to assess potential unmeasured confounding by comorbidities., Results: Patients treated with cryosurgery and thermal ablation had a statistically significant CSS benefit compared to those who deferred therapy (cryosurgery HR 0.25, 95% CI 0.14-0.45, p < 0.001; thermal ablation HR 0.27, 95% CI 0.13-0.55, p < 0.001, after adjustment for age at diagnosis, tumor grade, and size). There was no significant difference in CSS comparing cryosurgery to thermal ablation (HR 1.03, 95% CI 0.45-2.3, p = 0.95, after adjustment for age at diagnosis, tumor grade, and size). These results proved robust upon sensitivity analyses: After adjustment for comorbidities with varying prevalence assumptions, the corrected hazard ratio (cHR) of cryosurgery versus deferred therapy ranged between HR 0.09 and 0.68., Conclusion: Local ablative techniques provide relevant survival benefit and are preferable alternatives over deferred therapy. Cryosurgery and thermal ablation yield comparable outcomes., Level of Evidence: 2b according to the Oxford Centre for evidence-based medicine levels of evidence.

Background: Patient-reported health-related quality of life (HRQOL) differs between treatment options for prostate carcinoma. Long-term HRQOL data in brachytherapy series are scarce. Therefore, we analyzed prostate-specific and general HRQOL in patients treated with brachytherapy for prostate carcinoma after long-term follow-up., Methods: Two hundred ninety-six patients with prostate carcinoma were treated with brachytherapy (01/1998-11/2003). General and prostate-specific HRQOL were measured using EORTC-QLQ-C30 and EORTC-QLQ-PR25, respectively. Patients were asked to complete the questionnaires after a median follow-up of 141 (119-181) months. QLQ-C30 results were compared to the German reference population. QLQ-PR25 results were compared to an earlier follow-up after a median of 51 months (no published QLQ-PR25 reference population for comparison). Additionally, a literature review on HRQOL data in brachytherapy series was performed., Results: One hundred six (35.8%) patients were lost to follow-up, 70 (23.6%) had died. 120 (40.5%) patients were contacted. 80 questionnaires were returned (27% of the original cohort; 91% of alive patients were ≥70 years). Sexual activity declined over time (mean scores: 40.5 vs. 45.5; p = 0.006), hormonal treatment-related symptoms, problems associated with incontinence aids, and burden of obstructive urinary symptoms did not differ significantly compared to the 51-month follow-up. General HRQOL was numerically better in our cohort as compared to the German reference population (> 16% relative difference for both age strata; < 70 and ≥70 years)., Conclusions: Our results indicate that symptom-burden after long-term follow-up and associated prostate-specific HRQOL remains relatively stable from 51 to 141 months. General HRQOL in surviving patients was numerically better compared to the reference population.