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Daniele Castellani,1 Giacomo Maria Pirola,2 Emanuele Rubilotta,3 Marilena Gubbiotti,2 Simone Scarcella,1 Martina Maggi,4 Vineet Gauhar,5 Jeremy Yuen-Chun Teoh,6 Andrea Benedetto Galosi1 1Urology Division, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Polytechnic University of Le Marche, Ancona, Italy; 2Urology Division, San Donato Hospital, Arezzo, Italy; 3Urology Division, A.O.U.I. Verona University, Verona, Italy; 4Urology Division, La Sapienza University, Rome, Italy; 5Department of Urology, Ng Teng Fong General Hospital (NUHS), Singapore; 6S.H.Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, ChinaCorrespondence: Daniele CastellaniUrology Division, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Polytechnic University of Le Marche, via Conca 71, Ancona, 60126, ItalyTel +393471814691Fax +39715963367Email castellanidaniele@gmail.comAbstract: GreenLight laser™ photovaporization of the prostate (GLL-PVP) has become a valid alternative to traditional transurethral resection of the prostate (TURP) in men requiring surgery for benign prostatic hyperplasia. We aimed to review systematically the safety and efficacy of studies comparing GLL PVP and TURP in the medium-term. A comprehensive literature search was performed. Twelve studies were identified for meta-analysis. Meta-analyses showed a longer postoperative catheterization time (risk ratio (RR): 1.12, 95% CI:1.09– 1.14, p< 0.00001) and length of stay (RR: 1.16, 95% CI:1.12– 1.19, p< 0.00001) in the TURP group; higher risk of transfusion in the TURP group (RR: 6.51, 95% CI: 2,90– 14,64 p< 0.00001); no difference in the risk of urinary tract infections (RR: 0.83, 95% CI: 0.58– 1.18, p=0.30) and transient re-catheterization (RR: 1.11, 95% CI: 0.76– 1.60, p=0.60). Regarding reoperation rate, no difference was found in term of postoperative urethral stricture (RR: 1.13, 95% CI: 0.73– 1.75, p=0.59) and bladder neck contracture (RR: 0.66, 95% CI: 0.31– 1.40, p=0.28). A significantly higher incidence in reoperation for persistent/regrowth adenoma was present in the GLLL-PVP (RR: 0.64, 95% CI: 0.41– 0.99, p=0.05). Data at 2-year follow-up showed significant better post-voiding residual (PVR) (MD: -1.42, 95% CI: -2.01, -0.82, p< 0.00001) and International Prostate Symptom Score (IPSS) (MD: -0.35, 95% CI: -0.50, -0.20, p< 0.00001) after TURP. No difference was found in the mean PVR at 2 years after TURP, in the mean maximum flow rate (Qmax) (MD: 0.30, 95% CI: -0.02– 0.61, p=0.06) and quality of life QoL score (MD: 0.05, 95% CI: -0.02– 0.42, p=0.13). At 5-year follow-up, data showed better IPSS (MD: -1.70, 95% CI: -2.45,-0.95, p< 0.00001), QoL scores (MD: -0.35, 95% CI: -0.69, -0.02, p=0.04) and Qmax (MD: 3.29, 95% CI: 0.19– 6.38, p=0.04) after TURP. Data of PVR showed no significant difference (MD: -11.54, 95% CI: -29.55– 6.46, p=0.21). In conclusion, our analysis shows that GLL-PVP is a safer and more efficacious procedure than standard TURP in the early and medium-term. However, in the long term period GLL-PVP showed a higher incidence of reoperation rate due to incomplete vaporization/regrowth of prostatic adenoma.Keywords: benign prostatic hyperplasia, GreenLight laser photoselective vaporisation of the prostate, transurethral resection of the prostate, safety, efficacy, transurethral surgery

Purpose of Review: Renal cell carcinoma (RCC) is resistant to chemotherapy. Adjuvant interferon and tyrosine kinase inhibitors were ineffective. Immune checkpoint inhibitors (ICIs), however, have shed new hope in this setting. In the current review, updated evidence of adjuvant therapy in RCC is summarized., Recent Findings: KEYNOTE-564 demonstrated survival benefits of adjuvant Pembrolizumab in RCC. EAU guidelines now recommend adjuvant pembrolizumab to ccRCC patients at an increased risk of recurrence, as defined in the study. At a median follow-up of 24 months, the disease-free survival (DFS) was significantly longer for the Pembrolizumab group than placebo group [DFS 77.3 vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval (95% CI), 0.53-0.87; P = 0.002]. From its updated analysis, at median follow up of 57.2 months, overall survival (OS) benefit of Pembrolizumab was demonstrated (hazard ratio for death, 0.62; 95% CI, 0.44-0.87; P = 0.005). A number of other adjuvant ICI trials have though been negative., Summary: Pembrolizumab is currently the only adjuvant therapy for RCC showing survival benefits, amid a number of negative trials on adjuvant immunotherapy. Currently, there is no role for adjuvant tyrosine-kinase inhibitors and radiotherapy for RCC. Meanwhile, a multidisciplinary approach and shared decision-making should be adopted., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Objective: Kidney-sparing surgery (KSS) for upper tract urothelial cancer (UTUC) has gained increasing interest recently. However, there is limited contemporary data regarding the role of KSS in ureteral urothelial carcinoma. Therefore, we investigated the survival outcomes of ureteral urothelial carcinoma after KSS from a large, prospective international UTUC registry. Methods: The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included patients with UTUC who received KSS or radical nephroureterectomy (RNU) between 2014 and 2019. In this study, we included patients with ureteral UTUC only. Study outcomes included overall survival (OS), cancer-specific survival (CSS), upper tract recurrence-free survival (RFS), intravesical RFS, progression-free survival (PFS), and metastasis-free survival (MFS). Propensity score matching (PSM) was performed to balance the tumor features' differences between groups. Results: Of the 391 patients with ureteral UTUC, 309 (79.0%) received RNU and 82 (21.0%) received KSS by ureteroscopy with laser ablation ( n = 28) or segmental resection ( n = 54). After PSM, there were no differences in OS ( p = 0.525), CSS ( p = 0.487), upper tract RFS ( p = 0.147), intravesical RFS ( p = 0.989), PFS ( p = 0.617), and MFS ( p = 0.336) between KSS and RNU. There were no significant differences between ureteroscopic ablation and segmental resection in OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumor locations following segmental resection. Conclusions: In patients with ureteral UTUC, no significant differences in long-term survival outcomes were observed between KSS and RNU. Proximal ureteral UTUC had worse survival outcomes over other tumor locations following segmental resection.

Introduction: Focal therapy (FT) is a promising alternative to whole-gland treatments for Localized Prostate Cancer. Ten different FT modalities have been described in literature. However, FT is not yet recommended by the International Guidelines, due to the lack of robust data on Oncological Outcomes. The objective of our Narrative Review is to evaluate the oncological profile of the available FT modalities and to offer a comprehensive overview of the definitions of Cancer Control for FT., Material and Methods: Literature search was performed on 21 st  February 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole gland-treatments were excluded. All articles reporting oncological outcomes were included., Results: One-hundred-twenty-four studies, reporting data on more than 8000 patients treated with FT, were included. Overall, 40 papers were on High Intensity Focal Ultrasound (HIFU), 24 on Focal Cryotherapy, 13 on Irreversible Electroporation (IRE), 11 on Focal brachytherapy, 10 on Focal Laser Ablation (FLA), 8 on Photo-Dynamic Therapy (PDT), 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation (bRFA), 1 on Prostatic Artery Embolization (PAE) and 9 comparative papers. Overall, the Biochemical Recurrence (BCR) rate ranged from 0% (Focal Brachytherapy) to 67.5% (HIFU); the Salvage treatment rate ranged from 1% (IRE) to 54% (HIFU) considering re-treatment with FT and from 0% (Focal Brachytherapy) to 66.7% considering standard Radical Treatments. There is no univocal definition of Cancer Control, however the "Phoenix criteria" for BCR were the most commonly used., Conclusions: FT is a promising alternative treatment for localized prostate cancer in terms of Oncological Outcomes, however there is a wide heterogeneity in the definition of cancer control, the reporting of oncological outcomes and a lack of high-quality clinical trials. Solid comparative studies with standard treatments and an unambiguous consensus on how to describe Cancer Control in the field of Focal Therapy are needed., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Focal therapy (FT) is a promising alternative with curative intent for Low- to Intermediate-risk localized Prostate Cancer (PCa), claiming better functional outcomes and safety profile than standard whole-gland treatments. Ten different FT modalities have been described in the literature. The objective of our narrative review is to evaluate the safety profile and functional outcomes of these different modalities and the current most used tools of assessment for those outcomes., Material and Methods: Literature search was performed on 21st February 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole-gland treatments were excluded. All articles reporting functional outcomes were included., Results: One-hundred-seven studies, reporting data on 6933 patients, were included (26 on High Intensity Focal Ultrasound, 22 on Focal Cryotherapy, 14 on Irreversible Electroporation, 11 on Focal brachytherapy, 10 on Focal Laser Ablation, 8 on Photodynamic Therapy, 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation, 1 on Prostatic Artery Embolization, and 7 studies comparing different FTs). Post-operative pad-free rate ranged between 92.3-100%. Greater heterogeneity exists considering the Change in Erectile Function, with Changing in Erectile function- rates ranging between 0-94.4% (Cryotherapy). The most used Patient-Reported Outcome Measures (PROMs) were the International Prostate Symptom Score and the International Index of Erectile Function for incontinence/urinary function and potency, respectively. The most common reported complications were hematuria, infections, and urethral strictures, with rates widely ranging among different treatments. The Clavien-Dindo Classification was the most used (40/88 papers) to describe adverse events., Conclusion: FT is a promising treatment for localized PCa, achieving excellent results in terms of safety and functional outcomes. There is a wide heterogeneity in the definition of PROMS and time of collection between studies. High quality comparative studies with standard treatments are needed to reinforce these findings., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objective: Management of low-grade (LG) urothelium-confined (Ta stage) non-muscle-invasive bladder cancer (NMIBC) poses a distinct therapeutic challenge. Transurethral resection of bladder tumor (TURBT), the standard treatment, frequently has to be repeated because of high tumor recurrence rates. This places a considerable strain on both patients and health care infrastructure, underscoring the need for alternative management approaches. Herein, the IBCG (International Bladder Cancer Group), conducted a review to explore the efficacy and safety of deintensified treatment strategies for recurrent LG Ta NMIBC., Methods: We conducted a collaborative review of relevant literature in the PubMed/MEDLINE and Cochrane CENTRAL databases. Our focus was on high-quality evidence, including randomized controlled trials, systematic reviews, and meta-analyses. We also reviewed guidelines published by prominent urological associations., Key Findings and Limitations: Active surveillance, chemoablation, and office fulguration are valid treatment options for recurrent LG Ta NMIBC. These deintensified approaches offer several advantages over TURBT: lower complication rates, less morbidity, lower health care costs, and better quality of life for patients. Importantly, these benefits are achieved without compromising oncological safety., Conclusions and Clinical Implications: Our review demonstrates that less intensive treatment strategies for recurrent LG Ta NMIBC are both feasible and valuable. The IBCG recommends use of these approaches for carefully selected patients to help lower health care costs and enhance patients' quality of life., Patient Summary: We reviewed studies on less invasive management options for low-grade noninvasive bladder cancer, including active surveillance, chemical ablation, and heat treatment. Recent results confirm that these less intense treatment options can reduce the treatment burden and costs for patients and preserve their quality of life without negatively affecting cancer control outcomes., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) encompasses a broad spectrum of disease, with heterogeneous outcomes in terms of disease recurrence and progression. The International Bladder Cancer Group (IBCG) recently proposed an updated scoring model for IR substratification that is based on five key risk factors. Our aim was to provide a clinical validation of the IBCG scoring system and substratification model for IR NMIBC., Methods: This was an international multicenter retrospective study. Patients diagnosed with IR NMIBC between 2012 and 2022 and treated with transurethral resection of the bladder and adjuvant intravesical chemotherapy were included. According to the presence or absence of risk factors, patients with IR NMIBC were further categorized in IR-low (no risk factors), IR-intermediate (1-2 risk factors), and IR-high (≥3 risk factors) groups. The 1-yr and 3-yr rates for recurrence-free survival (RFS) and progression-free survival (PFS) were evaluated for each subgroup. Cox regression analyses were used to compare oncological outcomes between the groups., Key Findings and Limitations: Of the 677 patients with IR NMIBC included in the study, 231 (34%), 364 (54%), and 82 (12%) were categorized in the IR-low, IR-intermediate, and IR-high groups, respectively. There were significant differences in RFS and PFS rates between these groups., Conclusions and Clinical Implications: We provide the first clinical validation of the IBCG scoring system and model for substratification of IR NMIBC., Patient Summary: Our study demonstrates that patients with intermediate-risk non-muscle-invasive bladder cancer can be correctly classified into three distinct subgroups according to their risk of both disease recurrence and progression. Our results support use of this scoring system in clinical practice., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objective: Current management options for localized prostate cancer (PCa) include radical prostatectomy (RP), radiotherapy (RT), and active surveillance (AS). Despite comparable oncological outcomes, there is still lack of evidence on their comparative effectiveness in terms of patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). We conducted a systematic review of studies comparing PROMs and PREMs after all recommended management options for localized PCa (RP, RT, AS)., Methods: A literature search was performed in the MEDLINE, EMBASE, and Cochrane CENTRAL databases in accordance with recommendations from the European Association of Urology Guidelines Office and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All prospective clinical trials reporting PROMs and/or PREMs for comparisons of RP versus RT versus AS were included. A narrative synthesis was used to summarize the review findings. No quantitative synthesis was performed because of the heterogeneity and limitations of the studies available., Key Findings and Limitations: Our findings reveal that RP mostly affects urinary continence and sexual function, with better results for voiding symptoms in comparison to other treatments. RT was associated with greater impairment of bowel function and voiding symptoms. None of the treatments had a significant impact on mental or physical quality of life. Only a few studies reported PREMs, with a high rate of decision regret for all modalities (up to 23%)., Conclusions and Clinical Implications: All recommended treatments for localized PCa have an impact on PROMs and PREMs, but for different domains and with differing severity. We found significant heterogeneity in PROM collection, so standardization in real-world practice and clinical trials is warranted. Only a few studies have reported PREMs, highlighting an unmet need that should be explored in future studies., Patient Summary: We reviewed differences in patient reports of their outcomes and experiences after surgical prostate removal, radiotherapy, or active surveillance for prostate cancer. We found differences in the effects on urinary, bowel, and sexual functions among the treatments, but no difference for mental or physical quality of life. Our results can help doctors and prostate cancer patients in shared decision-making., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The narrower focal zone (FZ) size of modern lithotripter was considered as one of the factors that resulted in suboptimal treatment result of extracorporeal shockwave lithotripsy (SWL). Therefore, we investigate the efficacy and safety of standard narrow or extended (FZ) sizes in SWL for patients with renal stones. Materials and Methods: In this prospective study conducted between April 2018 and October 2022, patients with renal stones were randomized to receive SWL with either standard or extended FZ. Treatment was delivered using a Modulith SLX-F2 lithotripter with a maximum of 3000 shocks at 1.5 Hz. The primary outcome was treatment success 12 weeks after a single SWL session, defined as the absence of a stone or stone fragment <4 mm on computed tomography. Secondary outcomes included the incidence of perinephric hematoma, stone-free rate (SFR), and changes in the urinary levels of acute renal injury markers. Results: A total of 320 patients were recruited, and 276 patients were randomized into the two groups. The two groups had similar baseline parameters. The treatment success rate was significantly better for standard FZ (74.3%) than the extended FZ group (59.3%) ( p  = 0.009). Standard FZ also had a significantly better SFR (Grade-A, 36.8% vs 23.0%, p  = 0.013) and less pain after treatment. Both groups had similar perinephric hematoma formation rates, unplanned hospital admission rates, and changes in urinary acute renal injury markers. Conclusions: The standard narrow FZ has better treatment efficacy and similar safety compared with the extended FZ during SWL for renal stones. This clinical trial has been registered in the public domain (CCRBCTR) under trial number CUHK&#95;CCRB00510.

Background: Endoscopic enucleation of the prostate (EEP) has gained acceptance as an equitable alternative to transurethral resection of the prostate for benign prostate hyperplasia (BPH). Our primary aim is to compare peri-operative outcomes of EEP using thulium fiber laser (TFL) against high-power holmium laser (HPHL) in hands of experienced surgeons for large prostates (≥80 ml in volume). Secondary outcomes were assess complications within 1 year of follow up., Materials and Methods: We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with TFL or HPHL in 13 centers (January 2019-January 2023). Patients with prostate volume ≥80 ml were included, while those with concomitant prostate cancer, previous prostate/urethral surgery, and pelvic radiotherapy were excluded., Results: Of 1,929 included patients, HPHL was utilized in 1,459 and TFL in 470. After propensity score matching (PSM) for baseline characteristics, 247 patients from each group were analyzed. Overall operative time (90 [70, 120] vs. 52.5 [39, 93] min, P  < 0.001) and enucleation time (90 [70, 105] vs. 38 [25, 70] min, P  < 0.001) were longer in the TFL group, with comparable morcellation time (13 [10, 19.5] vs. 13 [10, 16.5] min, P  = 0.914). In terms of postoperative outcomes, there were no differences in 30-day complications such as acute urinary retention, urinary tract infection or sepsis. In the PSM cohort, univariable analyses showed that higher age, lower preoperative Qmax, higher preoperative PVRU, and longer operation time were associated with higher odds of postoperative incontinence, while 2-lobe enucleation had lower odds of incontinence compared to 3-lobe enucleation., Conclusions: This real-world study reaffirms that HPHL and TFL in large prostates are equally efficacious in terms of 30-day complications. TFL with the en-bloc technique has a shorter operative time which significantly improves short- and medium-term functional outcomes., (© 2024 The Asian Pacific Prostate Society. Published by Elsevier B.V.)

Aims: This study aimed to devise and validate a clinical scoring system for risk prediction of bladder cancer to guide urgent cystoscopy evaluation among people with diabetes., Methods: People with diabetes who received cystoscopy from a large database in the Chinese population (2009-2018). We recruited a derivation cohort based on random sampling from 70% of all individuals. We used the adjusted odds ratios (aORs) for independent risk factors to devise a risk score, ranging from 0 to 5: 0-2 'average risk' (AR) and 3-5 'high risk' (HR)., Results: A total of 5905 people with diabetes, among whom 123 people with BCa were included. The prevalence rate in the derivation (n  = 4174) and validation cohorts (n  = 1731) was 2.2% and 1.8% respectively. Using the scoring system constructed, 79.6% and 20.4% in the derivation cohort were classified as AR and HR respectively. The prevalence rate in the AR and HR groups was 1.57% and 4.58% respectively. The risk score consisted of age (18-70: 0; >70: 2), male sex (1), ever/ex-smoker (1) and duration of diabetes (≥10 years: 1). Individuals in the HR group had 3.26-fold (95% CI = 1.65-6.44, p  = 0.025) increased prevalence of bladder than the AR group. The concordance (c-) statistics was 0.72, implying a good discriminatory capability of the risk score to stratify high-risk individuals who should consider earlier cystoscopy., Conclusions: The risk prediction algorithm may inform urgency of cystoscopy appointments, thus allowing a more efficient use of resources and contributing to early detection of BCa among people planned to be referred., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: Artificial intelligence (AI) is a promising tool in pathology, including cancer diagnosis, subtyping, grading, and prognostic prediction., Methods: The aim of the study is to assess AI application in prostate cancer (PCa) histology. We carried out a systematic literature search in 3 databases. Primary outcome was AI accuracy in differentiating between PCa and benign hyperplasia. Secondary outcomes were AI accuracy in determining Gleason grade and agreement among AI and pathologists., Results: Our final sample consists of 24 studies conducted from 2007 to 2021. They aggregate data from roughly 8000 cases of prostate biopsy and 458 cases of radical prostatectomy (RP). Sensitivity for PCa diagnostic exceeded 90% and ranged from 87% to 100%, and specificity varied from 68% to 99%. Overall accuracy ranged from 83.7% to 98.3% with AUC reaching 0.99. The meta-analysis using the Mantel-Haenszel method showed pooled sensitivity of 0.96 with I 2  = 80.7% and pooled specificity of 0.95 with I 2  = 86.1%. Pooled positive likehood ratio was 15.3 with I 2  = 87.3% and negative - was 0.04 with I 2  = 78.6%. SROC (symmetric receiver operating characteristics) curve represents AUC = 0.99. For grading the accuracy of AI was lower: sensitivity for Gleason grading ranged from 77% to 87%, and specificity from 82% to 90%., Conclusions: The accuracy of AI for PCa identification and grading is comparable to expert pathologists. This is a promising approach which has several possible clinical applications resulting in expedite and optimize pathology reports. AI introduction into common practice may be limited by difficult and time-consuming convolutional neural network training and tuning., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To perform a systematic review and meta-analysis to evaluate the impact of body mass index (BMI) on oncological (primary) and surgical (secondary) outcomes of patients who underwent nephrectomy, as obesity or high BMI is a known risk factor for renal cell carcinoma (RCC) and predictor of poorer outcomes., Methods: Studies were identified from four electronic databases from database inception to 2 June 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. The review protocol was registered in the International Prospective Register of Systematic Reviews with the identification number: CRD42021275124., Results: A total of 18 studies containing 13 865 patients were identified for the final meta-analysis. Regarding oncological outcomes, higher BMI predicted higher overall survival (BMI >25 vs BMI <25 kg/m 2 : hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.58-0.85), cancer-specific survival (BMI >25 vs BMI <25 kg/m 2 : HR 0.60, 95% CI 0.50-0.73; BMI 25-30 vs BMI <25 kg/m 2 : HR 0.46, 95% CI 0.23-0.95; BMI >30 vs BMI <25 kg/m 2 : HR 0.50, 95% CI 0.36-0.69), and recurrence-free survival rates (BMI >25 vs BMI <25 kg/m 2 : HR 0.72, 95% CI 0.63-0.82; BMI 25-30 vs BMI <25 kg/m 2 : HR 0.59, 95% CI 0.42-0.82). Those with a lower BMI fared better in surgical outcomes, such as operation time and warm ischaemic time, although the absolute difference was minimal and unlikely to be clinically significant. There was no difference between groups for length of hospital stay, intraoperative or postoperative complications, blood transfusion requirements, and conversion to open surgery., Conclusion: Our study suggests that a higher BMI is associated with improved long-term oncological survival and similar perioperative outcomes as a lower BMI. More research into the underlying biological and physiological mechanisms will enable better understanding of the effect of BMI, beyond mere association, on post-nephrectomy outcomes., (© 2023 BJU International.)

Background: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques., Methods: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared., Results: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group ( p = 0.034). Blood loss was higher in the ORC group ( p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group ( p = 0.003). Length of stay was longer in the ORC group ( p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference ( p = 0.033) found in the univariate analysis., Conclusion: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

Introduction: We conducted translation and psychometric validation of a self-administered, 22-item dichotomous response-based questionnaire to identify nocturia aetiologies and co-morbidities in adult patients., Methods: The Targeting the individual's Aetiology of Nocturia to Guide Outcomes (TANGO) questionnaire was forward- and backward-translated, then finalised using a standardised methodology. The resulting version, a Chinese version of the TANGO [TANGO (CV)], was evaluated for internal consistency, test-retest reliability, content validity, convergent validity, criterion validity, and discriminant validity via responses from 65 participants (46 men and 19 women; mean age, 67 years, range, 50-88), in comparison with other validated questionnaires and a 4-day bladder/sleep diary., Results: Only 0.4% of responses were missing; 3% of participants required assistance with comprehension. The Kuder-Richardson Formula 20 (KR-20) coefficient for the whole tool was 0.711. Kappa values for individual domains and the whole tool varied from 0.871 to 0.866, indicating satisfactory test-retest reliability. There was strong agreement between the sum of positive responses to each domain and the whole tool (intra-class correlation coefficient=0.878-1.000). Modest correlations (ρ=0.4-0.6) were detected between the tool and bladder/sleep diary-based parameters for convergent validity. Criterion validity was confirmed for each domain and the whole tool [ρ=0.287-0.687]. In receiver operating characteristic analysis, the tool could distinguish patients (≥2 nocturia episodes/night) from controls (≤1 nocturia episode/night) [Youden's J statistic=0.453, area under the curve=0.818, 95% confidence interval (CI)=0.683-0.953] and patients with significant nocturia distress from patients with mild nocturia distress (Youden's J statistic=0.398, area under the curve=0.729, 95% CI=0.581-0.878)., Conclusion: The TANGO (CV) was formally crossculturally adapted and translated. Its psychometric properties (except sensitivity to change) were validated., Competing Interests: As editors of the journal, CF Ng and JYC Teoh were not involved in the peer review process. Other authors have disclosed no conflicts of interest.

Introduction: Prostate-specific antigen-based screening for prostate cancer reportedly does not improve cancer-specific survival. However, there remain concerns about the increasing incidence of advanced disease at initial presentation. Here, we investigated the incidences and types of complications that occur during the course of disease in patients with metastatic hormone-sensitive prostate cancer (mHSPC)., Methods: This study included 100 consecutive patients who were diagnosed with mHSPC at five hospitals from January 2016 to August 2017. Analyses were conducted using patient data extracted from a prospectively collected database, along with information about complications and readmission obtained from electronic medical records., Results: The median patient age was 74 years and the median serum prostate-specific antigen level at diagnosis was 202.5 ng/mL. Ninety-nine patients received androgen deprivation therapy; 17 of these patients also received chemotherapy. During a mean follow-up period of 32.9 months, 41 patients reported bone pain; of these patients, 21 developed pathologic fractures and eight had cord compression. Twenty-eight patients developed retention of urine; of these patients, 10 (36%) required surgery and 11 (39%) required long-term urethral catheter use. Among 15 patients who developed ureteral obstruction, four (27%) required ureteral stenting and four (27%) required long-term nephrostomy drainage. Other complications included anaemia (41%) and deep vein thrombosis (4%). Fifty-nine (59%) patients had ≥1 unplanned hospital admission during the course of disease; 16% of such patients had >5 episodes of readmission., Conclusion: Among patients with mHSPC, 70% experienced disease-related complications and unplanned hospital admissions, which substantially burdened both patients and the healthcare system., Competing Interests: As editors of the journal, CF Ng and JYC Teoh were not involved in the peer review process. Other authors have disclosed no conflicts of interest.

Background: Vaspin is an adipokine that regulates glucose and lipid metabolism. Plasma vaspin level is increased in chronic kidney disease but decreased in hemodialysis patients. However, plasma vaspin level in peritoneal dialysis (PD) patients, as well as its prognostic role, has not been studied., Methods: We recruited 146 incident PD patients. Their baseline plasma vaspin levels, body anthropometry, the profile of insulin resistance, bioimpedance spectroscopy parameters, dialysis adequacy, and nutritional indices were measured. They were followed for up to 5 years for survival analysis., Results: The average age was 58.4 ± 11.8 years; 96 patients (65.8%) were men, and 90 (61.6%) had diabetes. The median vaspin level was 0.18 ng/dL (interquartile range [IQR] 0.11 to 0.30 ng/dL). Plasma vaspin level did not have a significant correlation with adipose tissue mass or baseline insulin level. However, plasma vaspin level had a modest correlation with the change in insulin resistance, as represented by the HOMA-IR index, in non-diabetic patients (r = -0.358, p = 0.048). Although the plasma vaspin level quartile did not have a significant association with patient survival in the entire cohort, it had a significant interaction with diabetic status (p < 0.001). In nondiabetic patients, plasma vaspin level quartile was an independent predictor of patient survival after adjusting for confounding clinical factors (adjusted hazard ratio 2.038, 95% confidence interval 1.191-3.487, p = 0.009), while the result for diabetic patients was not significant., Conclusions: Plasma vaspin level quartile had a significant association with patient survival in non-diabetic PD patients. Baseline plasma vaspin level also had a modest inverse correlation with the subsequent change in the severity of insulin resistance, but the exact biological role of vaspin deserves further studies., (© 2023. The Author(s).)

Background: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) has seen a rising trend. We investigated the relationship between ADT and adverse changes in metabolic parameters in an Asian population., Methods: This is an international prospective multicenter single-arm cohort yielded from the real-life experience of ADT in Asia (READT) registry. Consecutive ADT-naïve patients diagnosed of PCa and started on ADT were prospectively recruited from 2016 and analyzed. Baseline patient characteristics, PCa disease status, and metabolic parameters were documented. Patients were followed up at 6-month interval for up to 5 years. Metabolic parameters including body weight, lipid profiles, and glycemic profiles were recorded and analyzed., Results: 589 patients were eligible for analysis. ADT was associated with adverse glycemic profiles, being notable at 6 months upon ADT initiation and persisted beyond 1 year. Comparing to baseline, fasting glucose level and hemoglobin A1c level increased by 4.8% (p < 0.001) and 2.7% (p < 0.001), respectively. Triglycerides level was also elevated by 16.1% at 6th month and by 20.6% at 12th month compared to baseline (p < 0.001). Mean body weight was 1.09 kg above baseline at 18th month (p < 0.001)., Conclusion: ADT was associated with adverse metabolic parameters in terms of glycemic profiles, lipid profiles, and body weight in the Asian population. These changes developed early in the treatment and can persist beyond the first year. Regular monitoring of the biochemical profiles during treatment is paramount in safeguarding the patients' metabolic health., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Introduction: Didactic lectures have been the foundation of learning for many medical students. However, in recent years, the flipped classroom model has become increasingly popular in medical education. This approach enhances pre-class learning, allowing the limited contact time between clinicians and medical students to be focused on practical issues. This study evaluated the effectiveness and non-inferiority of online micromodule teaching in terms of knowledge transfer concerning specific urology topics., Methods: Medical students without prior exposure to the urology subspecialty were enrolled in the study, then randomised to a traditional didactic lecture group or an online micromodule group. Knowledge transfer was assessed by pre-intervention and post-intervention multiple-choice questions and objective structured clinical examinations that involved the acquisition of medical histories from real patients., Results: In total, 45 medical students were enrolled (22 in the traditional didactic group and 23 in the online micromodule group). In terms of knowledge transfer (assessed by objective structured clinical examinations), the efficacy of online micromodules was comparable to traditional didactic lectures, although the difference was not statistically significant (P=0.823). There were no significant differences in terms of knowledge acquisition, retention, or clinical application between the two groups., Conclusion: In terms of acquiring, retaining, and applying foundational urological knowledge, online micromodules can help medical students to achieve outcomes comparable with the outcomes of didactic lectures. Online micromodules may be a viable alternative to traditional didactic lectures in urology education., Competing Interests: As editors of the journal, CF Ng and JYC Teoh were not involved in the peer review process. Other authors have disclosed no conflicts of interest.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to an increase in global awareness of relevant public health preventive measures. This awareness can be explored using online search trends from major search engines, such as Google Trends. We investigated the relationship between public awareness of preventative measures and progression of the COVID-19 pandemic., Methods: Search data for five queries ('mask', 'hand washing', 'social distancing', 'hand sanitizer', and 'disinfectant') were extracted from Google Trends in the form of relative search volume (RSV). Global incidence data for COVID-19 were obtained from 1 January to 30 June 2020. These data were analysed and illustrated using a global temporal RSV trend diagram, a geographical RSV distribution chart, scatter plots comparing geographical RSV with average number of daily cases, and heat maps comparing temporal trends of RSV with average number of daily cases., Results: Global temporal trends revealed multiple increases in RSV, associated with specific COVID-19-related news events. The geographical distribution showed top regions of interest for various preventive measures. For the queries 'mask', 'hand washing', 'hand sanitizer', and 'disinfectant', heat maps demonstrated patterns of early RSV peaks in regions with lower average number of daily cases, when the temporal element was incorporated into the analysis., Conclusion: Early public awareness of multiple preventive measures was observed in regions with lower average number of daily cases. Our findings indicate optimal public health communication regarding masks, hand washing, hand sanitiser, and disinfectant in the general population during early stages of the COVID-19 pandemic. Early public awareness may facilitate future disease control efforts by public health authorities., Competing Interests: As editors of the journal, CF Ng, MCS Wong and JYC Teoh were not involved in the peer review process. Other authors have disclosed no conflicts of interest.

Competing Interests: As the Editor-in-Chief and an editor of the journal respectively, MCS Wong and JYC Teoh were not involved in the peer review process. Other authors have disclosed no conflicts of interest.

Xanthogranulomatous pyelonephritis (XGP) is an uncommon chronic granulomatous infection of renal parenchyma. XGP is often associated with long-term urinary tract obstruction due to stones and infection. We aimed to analyze the clinical, laboratory, and microbial culture profiles from bladder and kidney urine of patients who were diagnosed with XGP. Databases of patients with histopathological diagnosis of XGP from 10 centers across 5 countries were retrospectively reviewed between 2018 and 2022. Patients with incomplete medical records were excluded. A total of 365 patients were included. There were 228 (62.5%) women. The mean age was 45 ± 14.4 years. The most common comorbidity was chronic kidney disease (71%). Multiple stones were present in 34.5% of cases. Bladder urine culture results were positive in 53.2% of cases. Kidney urine culture was positive in 81.9% of patients. Sepsis and septic shock were present in 13.4% and 6.6% of patients, respectively. Three deaths were reported. Escherichia coli was the most common isolated pathogen in both urine (28.4%) and kidney cultures (42.4%), followed by Proteus mirabilis in bladder urine cultures (6.3%) and Klebsiella pneumoniae (7.6%) in kidney cultures. Extended-spectrum beta-lactamases producing bacteria were reported in 6% of the bladder urine cultures. On multivariable analysis, urosepsis, recurrent urinary tract infections, increased creatinine, and disease extension to perirenal and pararenal space were independent factors associated with positive bladder urine cultures. On multivariable analysis, only the presence of anemia was significantly more frequent in patients with positive kidney cultures. Our results can help urologists counsel XGP patients undergoing nephrectomy.

Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress.

Rationale & Objective: Omentin-1 is an adipokine with anti-inflammatory and cardioprotective properties. The objective of this study was to determine the prognostic role of plasma omentin-1 levels in incident peritoneal dialysis (PD) patients., Study Design: Retrospective analysis of prospective cohort., Setting & Participants: 152 incident PD patients., Predictors: Plasma omentin-1 level, adipose tissue omentin-1 messenger RNA (mRNA) expression., Outcomes: Patient survival, technique survival, hospital admission, and duration of stay., Analytical Approach: Time-to-event survival analyses; linear regression for hospitalization., Results: The mean age was 58.4 ± 11.7 years; 102 were men, and 92 had diabetes. There was no significant correlation between plasma omentin-1 level and its adipose tissue mRNA expression. A higher plasma omentin-1 level quartile was not associated with patient survival ( P  = 0.92) or technique survival ( P  = 0.83) but had a modest correlation with a lower number of hospital admissions ( P  = 0.07) and shorter duration of hospital stay ( P  = 0.04). In adjusted models using multivariable linear regression, a higher plasma omentin-1 level quartile remained significantly associated with fewer hospital admissions (β, -0.13; 95% CI, -0.26 to -0.002; P  = 0.05) and shorter hospitalization duration (β, -0.20; 95% CI, -0.38 to -0.02; P  = 0.03)., Limitations: Observational study with baseline measures only., Conclusions: Plasma omentin-1 level was not associated with patient survival, technique survival, or peritonitis, but higher plasma omentin-1 levels were associated with fewer hospital admissions and shorter duration of hospitalization among incident PD patients., (© 2023 The Authors.)

Rationale & Objective: Cardiovascular disease is the major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Adiponectin, a key adipokine, is related to obesity and insulin resistance. We determined the clinical and prognostic value of plasma adiponectin level and its adipose tissue messenger RNA (mRNA) expression in new PD patients., Study Design: Retrospective analysis of a prospective observational study., Setting & Participants: 152 new PD patients from a single center; 6 adults undergoing abdominal surgeries without kidney disease served as controls., Predictors: Plasma adiponectin level and its adipose tissue mRNA expression., Outcomes: Body build and composition, patient and technique survival., Analytical Approach: Adiponectin level and mRNA expression were grouped in quartiles for correlation analysis for body build and Cox regression for survival analysis., Results: The median plasma adiponectin level was 31.98 μg/mL (IQR, 16.81-49.49 μg/mL), and adiponectin mRNA expression in adipose tissue was 1.65 times higher than in controls (IQR, 0.98-2.63). There was a modest but statistically significant correlation between plasma adiponectin and its adipose tissue mRNA expression ( r   =  0.40, P  < 0.001). Plasma adiponectin level inversely correlated with body mass index, waist-hip ratio, mid-arm circumference, adipose tissue mass, plasma triglyceride ( r  = -0.39, -0.38, -0.41, -0.38, and -0.30, respectively; P  < 0.001 for all), as well as serum insulin level ( r  = -0.24, P  = 0.005). Similar correlations were present but less marked with adipose tissue adiponectin mRNA level. Neither plasma adiponectin level nor adipose tissue adiponectin mRNA level predicted patient or technique survival., Limitations: Observational study, single center, single baseline measurement., Conclusions: Plasma adiponectin level correlated with the degree of adiposity in new PD patients. However, neither plasma adiponectin level nor its adipose tissue mRNA expression was an independent prognostic indicator in kidney failure patients newly started on PD., (© 2022 The Authors.)

Introduction: This systematic review and meta-analysis focused on the literature regarding ketamine-associated uropathy to summarise its clinical manifestations, the results of urological assessments, and current management., Methods: A literature search was conducted using keywords and MeSH terms related to ketamine abuse, urinary tracts, and urological examinations. Databases including Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched up to 26 June 2020., Results: In total, 1365 articles were retrieved; 45 articles (4921 patients) were included in the analysis of patient demographics, clinical manifestations, examination results, and treatments. Frequency was the most common manifestation (pooled prevalence 77.1%, 95% confidence interval [CI]=56.9%-92.2%), followed by urgency (69.9%, 95% CI=48.8%-87.3%) and suprapubic pain (60.4%, 95% CI=35.3%-82.9%). Upper urinary tract involvement was less common; the pooled prevalence of hydronephrosis was 30.2% (95% CI=22.0%-39.2%). Further workup revealed a pooled functional bladder capacity of 95.23 mL (95% CI=63.57-126.88 mL), pooled voided volume of 113.31 mL (95% CI=59.44- 167.19 mL), and pooled maximum urine flow rate of 8.69 mL/s (95% CI=5.54-11.83 mL/s). Cystoscopic examinations and bladder biopsy revealed frequent urothelial denudation, inflammatory changes, and inflammatory cell infiltration. Treatments included oral medications for symptomatic relief, intravesical therapy, and surgery (eg, hydrodistension and bladder reconstruction), but ketamine abstinence was necessary for improvement., Conclusion: Ketamine-associated uropathy frequently involves frequency, urgency, and suprapubic pain; upper urinary tract involvement is less common. Affected patients showed reductions in bladder capacity and urine flow rate. Endoscopic and histological analyses often revealed cystitis. Despite variations in treatment, ketamine abstinence is important for all patients with ketamine-associated uropathy., Competing Interests: As editors of the journal, MCS Wong, CF Ng, and JYC Teoh were not involved in the peer review process. Other authors have disclosed no conflicts of interest.

Background: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD., Methods: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD., Results: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57-3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08-2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80-13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13-12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006-0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02-0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35-50.5, p = 0.02)., Conclusion: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after PD.

Context: Platinum-based combination chemotherapy is the standard treatment for advanced or metastatic urothelial carcinoma (AMUC). However, data comparing the efficacy of different platinum agents are limited., Objective: This review aimed to assess the efficacy of carboplatin as a first-line treatment for AMUC using phase 3 randomized trial data., Evidence Acquisition: Multiple databases were searched for articles published until August 2021. Studies that compared overall survival (OS), complete response (CR), and objective response rates (ORRs) in chemotherapy-eligible patients with AMUC were deemed eligible., Evidence Synthesis: Four studies were included. Compared with immune checkpoint inhibitor (ICI) monotherapy, neither cisplatin- nor carboplatin-based chemotherapy was associated with significant OS (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.85-1.11, p = 0.64 and HR: 0.90, 95% CI: 0.78-1.04, p = 0.16, respectively) and CR (odds ratio [OR]: 1.16, 95% CI: 0.70-1.92, p = 0.57 and OR: 0.89, 95% CI: 0.52-1.53, p = 0.67, respectively benefits, while both were associated with a favorable ORR (OR: 0.54, 95% CI: 0.40-0.74, p < 0.001 and OR: 0.58, 95% CI: 0.42-0.80, p < 0.001, respectively). A network meta-analysis (NMA)-based indirect comparison between carboplatin and cisplatin revealed that while cisplatin was slightly better than carboplatin in terms of OS, CR, and ORR, no significant difference was noted., Conclusions: Cisplatin- and carboplatin-based chemotherapies offer similar OS/CR benefits to ICI monotherapy and elicit a greater ORR than ICI monotherapy. Moreover, our NMA demonstrated that both cisplatin- and carboplatin-based chemotherapy have a similar efficacy in terms of OS, CR, and ORR. Given that carboplatin-based chemotherapy is shown to be more effective in contemporary series than in historical controls, it is strongly recommended that carboplatin be re-examined for its value in the era of ICIs and beyond., Patient Summary: Cisplatin- as well as carboplatin-based chemotherapy is as effective as immune checkpoint inhibitors in terms of survival and eliciting a positive response. It is currently believed that cisplatin provides greater benefits than carboplatin; this requires re-evaluation., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The use of antibiotics may induce the changes in gut microbiota. Previous studies have shown conflicting results on whether the changed gut microbiota by antibiotics can be recovered. Our study aims to investigate whether the gut microbiota could be recovered after a single dose of oral co-amoxiclav before transrectal ultrasound-guided transperineal prostate biopsy (TPPBx) in 5 weeks' time., Methods: Fifteen patients with elevated serum prostate-specific antigen (PSA) were recruited to provide pre-antibiotic and post-antibiotic fecal samples. The V4 region of 16S rRNA was sequenced. Analysis was performed by QIIME2. Alpha- and beta-diversities were analyzed, as well as the differential enrichment by Linear discriminant analysis Effect Size (LEfSe) analysis., Results: Both the alpha- and beta-diversities of the pre- and post-antibiotic fecal samples were significantly different. Genera that are associated with alleviation of inflammation were enriched in the pre-antibiotic fecal samples, while the inflammation-associated genera were more enriched in the post-antibiotic fecal samples., Conclusion: A single dose of oral co-amoxiclav before TPPBx could have led to a change of gut microbiota that cannot be recovered in 5 weeks' time. Microbiome studies on prostate cancer patients should be cautioned on the use of post-prostate biopsy fecal sampling. Further studies should be conducted for the impact on gut microbiome for TPPBx alone., 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 Li, Wang, Lau, Tse, Cheng, Leung, Wong, Tsui, Teoh, Chiu and Ng.)

Purpose: This study aimed to investigate the functional and urodynamic outcome of Aquablation in patients with acute urinary retention (AUR) on catheters., Methods: Men aged 50-70 who failed medical treatment of BPO with AUR failing to wean off urethral catheter were recruited to undergo Aquablation. Individuals were assessed pre-operatively and at 3 and 6 months after surgery. The primary outcome was defined by the success rate of weaning off catheter. Secondary outcomes were measured by a change in prostate size, symptom scores and urodynamic parameters., Results: Twenty patients underwent Aquablation between June 2019 and September 2020. Mean duration of the urethral catheter in-situ was 5.9 ± 4.9 weeks and mean prostate size of the cohort pre-operatively was 60.8 ± 15.8 cc. A second pass Aqaublation treatment was performed in 14 patients. Five patients failed to wean off the catheter on the first attempt after surgery, requiring another attempt 1 week later which were all successful. At 3 months after the operation, a significant reduction in prostate volume was observed (60.8 ± 15.8 cc vs 24.9 ± 10.3 cc, p < 0.001). No change in international index of erectile function (IIEF) was found (baseline: 16.1 ± 5.8; 3-month: 14.9 ± 6.4; p = 0.953). Mean bladder outlet obstruction index was 14.2 ± 23.0 at 6 months upon urodynamic assessment with 75% of patients had a resolution of detrusor overactivity. Reduction in prostate length was found to be more significant than a reduction in width and height after Aquablation (R = 0.693, p = 0.039)., Conclusion: From the early data of a single centre, Aquablation was shown to provide a consistent improvement in symptoms, uroflowmetry and urodynamic parameters in patient with a urethral catheter. Results from our study suggest that improvement from Aquablation is reproducible in patients with AUR., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Urinary cell-free DNA (ucfDNA) is a potential biomarker for bladder cancer detection. However, the biological characteristics of ucfDNA are not well understood. We explored the roles of deoxyribonuclease 1 (DNASE1) and deoxyribonuclease 1-like 3 (DNASE1L3) in the fragmentation of ucfDNA using mouse models. The deletion of Dnase1 in mice (Dnase1-/-) caused aberrations in ucfDNA fragmentation, including a 24-fold increase in DNA concentration, and a 3-fold enrichment of long DNA molecules, with a relative decrease of fragments with thymine ends and reduction of jaggedness (i.e., the presence of single-stranded protruding ends). In contrast, such changes were not observed in mice with Dnase1l3 deletion (Dnase1l3-/-). These results suggested that DNASE1 was an important nuclease contributing to the ucfDNA fragmentation. Western blot analysis revealed that the concentration of DNASE1 protein was higher in urine than DNASE1L3. The native-polyacrylamide gel electrophoresis zymogram showed that DNASE1 activity in urine was higher than that in plasma. Furthermore, the proportion of ucfDNA fragment ends within DNase I hypersensitive sites (DHSs) was significantly increased in Dnase1-deficient mice. In humans, patients with bladder cancer had lower proportions of ucfDNA fragment ends within the DHSs when compared with participants without bladder cancer. The area under the curve (AUC) for differentiating patients with and without bladder cancer was 0.83, suggesting the analysis of ucfDNA fragmentation in the DHSs may have potential for bladder cancer detection. This work revealed the intrinsic links between the nucleases in urine and ucfDNA fragmentomics., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: K.C.A.C., R.W.K.C., and Y.M.D.L. hold equities in DRA, Take2, and Grail/Illumina. K.C.A.C., R.W.K.C., and Y.M.D.L. were consultants to Grail/Illumina. K.C.A.C., R.W.K.C., and Y.M.D.L. received research funding from Grail/Illumina. Y.M.D.L. was a scientific co-founder of and served on the scientific advisory board of Grail/Illumina. W.K.J.L and P.J. holds equities in Grail/Illumina. P.J. is a consultant to Take2. P.J. is a Director of KingMed Future.

Background: Elevated preoperative plasma levels of the angiogenesis-related marker VEGF have been associated with worse oncological outcomes in various malignancies., Objective: To investigate the predictive/prognostic role of VEGF in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC)., Design, Setting, and Participants: VEGF plasma levels were measured preoperatively in 1036 patients with UCB who underwent RC., Outcome Measurements and Statistical Analysis: The correlation between plasma VEGF levels and pathological and survival outcomes was assessed using logistic regression and Cox regression analyses. Discrimination was assessed using the concordance index (C index). The clinical net benefit was evaluated using decision curve analysis (DCA)., Results and Limitations: Patients with higher pretreatment plasma VEGF levels had poorer recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) according to log-rank tests (all p < 0.001). Higher VEGF levels were not independently associated with higher risk of lymph node metastasis, ≥pT3 disease, or non-organ-confined disease (all p > 0.05). Preoperative plasma VEGF levels were independently associated with RFS, CSS, and OS in preoperative and postoperative multivariable models. However, in all cases the C index increased by <0.02 and there was no improvement in net benefit on DCA. A limitation is that none of the patients received current elements of standard of care such as neoadjuvant chemotherapy., Conclusions: Elevated plasma VEGF levels were associated with features of biologically and clinically aggressive disease such as worse survival outcomes among patients with UCB treated with RC. However, VEGF appears to have relatively limited incremental additive value in clinical use. Further study of VEGF for UCB prognostication is warranted before routine use in clinical algorithms., Patient Summary: Currently available models for predicting outcomes in bladder cancer are less than optimal. A protein called vascular endothelial growth factor (VEGF), which is a marker of the formation of blood vessels (angiogenesis), may have a role in predicting survival outcomes in bladder cancer., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate the outcome of retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) compared with conventional RARP in the early learning curve., Methods: Consecutive patients with prostate cancer who underwent RS-RARP were included to compare against conventional RARP of the same period. Propensity-score matching was performed based on age, prostate size, nerve-sparing approach, and final pathological risk categories. All patients were re-admitted to undergo trial without Foley catheter from post-operative day 7-10. Clinical follow-up was performed with monitoring of continence (day 0, 3 months, and the latest continence during the study period) and surveillance of PSA level., Results: Between July 2017 and August 2019, 24 consecutive patients received RS-RARP in our centre. Propensity score matching was performed with the best matched 24 controls receiving conventional RARP. Overall median follow-up duration was 15.5 months. A majority of the patients belonged to the intermediate-risk group, with most of them harbouring pT2 disease (RS-RARP: 87.5%; conventional RARP: 79.2%). More patients in RS-RARP group achieved day-0 continence (33.3% vs 0%, p = 0.002) and 3-month continence (66.7% vs 12.5%, p = 0.001). During the whole study period, more RS-RARP achieved continence with 0 pad (91.7% vs 66.7%, p = 0.033). The mean months to continence is shorter in RS-RARP group (4.0 months vs 13.6 months, p = 0.002). No statistically significant differences between the two groups with respect to surgical margins, post-operative PSA detection, and the use of adjuvant radiotherapy., Conclusions: RS-RARP showed better continence rates when compared to conventional RARP even during the learning curve phase., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: To evaluate the outcomes of pre-stented (PS) versus non-pre-stented (NPS) patients who have undergone retrograde intrarenal surgery (RIRS) for renal calculi with subgroup analysis of Asian and non-Asian cohorts., Methods: Protocol is registered in PROSPERO, CRD42021261123. Eligible studies identified from four electronic databases. Meta-analysis was done to enumerate the outcomes of RIRS in between PS and NPS. Secondary sub-analysis was done to look for differences in outcomes in Asian and non-Asian cohorts., Results: Fourteen studies involving 3831 patients (4 prospective, 10 retrospective studies) were included. PS patients experienced higher success rates of ureteral access sheath (UAS) insertion than NPS (RR 1.09, 95% CI 1.05-1.13, p < 0.00001). PS patients had lower risk of ureteral injuries from UAS placement (RR 0.69, 95% CI 0.50-0.96, p = 0.03). No significant differences in intra- and postoperative complications between two groups were found. Stone-free rate (SFR) outcomes for residual fragment (RF) cut-off of < 1 mm and < 4 mm favoured the PS patients (RR 1.10, 95% CI 1.04-1.17, p = 0.002 for < 4 mm, RR1.10, 95% CI 1.02-1.19, p = 0.02 for < 1 mm). In the subgroup analysis, PS Asian patients had similar SFR as NPS patients for SFR(< 4 mm) but non-Asian population showed better outcomes in the PS patients for SFR(< 4 mm) (RR 1.31, 95% CI 1.13-1.52, p = 0.0005)., Conclusions: This meta-analysis suggests that pre-stenting results in a higher success for UAS placement, minimising intraoperative ureteric injury, with higher overall SFR for any RF cut-off in PS cohorts. In non-Asian cohort, significant differences occurred at SFR < 4 mm but not for SFR < 1 mm. No difference was seen in our Asian cohort for any SFR cut-off in both PS and NPS patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objective: The Clavien-Dindo Classification (CDC) only reports the postoperative complication of highest grade. It is thus of limited value for radical cystectomy, after which patients usually experience multiple complications. The Comprehensive Complication Index (CCI) is a novel scoring system, which incorporates all postoperative events in one single value. The study aimed to adopt the CCI for the evaluation of complications in patients undergoing robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) and explore its advantages in the analysis of the morbidity of RARC with ICUD. Patients and Methods: A multicentric cohort of 959 patients undergoing RARC+ICUD between 2015 and 2020, whose complications are encoded in local prospective registries. Postoperative complications at 30 days were assessed using both the CDC and CCI. The CCI was calculated using an online tool (assessurgery.com). Risk factors for overall, major complications (CDC ≥III), and CCI were evaluated using uni- and multivariable logistic and linear regressions. To analyze the potential advantage of using the CCI in clinical trials, a sample size calculation of a hypothetic clinical trial was performed using as endpoint reduction of morbidity with either the CDC or CCI. Results: Overall, 885 postoperative complications were reported in 507 patients (53%). The CCI improved the definition of postoperative morbidity in 22.6% of patients. Male sex and neobladder were associated with major complications and to a significant increase in CCI on adjusted regressions. In a hypothetical clinical trial, 80 patients would be needed to demonstrate a ten-point reduction in CCI, compared with 186 needed to demonstrate an absolute risk reduction of 20% in overall morbidity using the CDC. Conclusion: CCI improves the evaluation of postoperative morbidity by considering the cumulative aspect of complications compared with the CDC. Implementing the CCI for radical cystectomy would help reducing sample sizes in clinical trials. Clinical Trial Registration number: NCT03049410.

Background: Radical cystectomy (RC) is indicated in primary or secondary muscle-invasive bladder cancer (primMIBC, secMIBC) and in primary or recurrent high- or very high-risk non-muscle-invasive bladder cancer (primHR-NMIBC, recHR-NMIBC). The optimal timing for RC along the disease spectrum of nonmetastatic urothelial carcinoma remains unclear., Objective: To compare outcomes after RC between patients with primHR-NMIBC, recHR-NMIBC, primMIBC, and secMIBC., Design Setting and Participants: This retrospective, multicenter study included patients with clinically nonmetastatic bladder cancer (BC) treated with RC., Outcome Measurements and Statistical Analysis: We assessed oncological outcomes for patients who underwent RC according to the natural history of their BC. primHR-NMIBC and primMIBC were defined as no prior history of BC, and recHR-NMIBC and secMIBC as previously treated NMIBC that recurred or progressed to MIBC, respectively. Log-rank analysis was used to compare survival outcomes, and univariable and multivariable Cox and logistic regression analyses were used to identify predictors for survival., Results and Limitations: Among the 908 patients included, 211 (23%) had primHR-NMIBC, 125 (14%) had recHR-NMIBC, 404 (44%) had primMIBC, and 168 (19%) had secMIBC. Lymph node involvement and pathological upstaging were more frequent in the secMIBC group than in the other groups ( p  < 0.001). The median follow-up was 37 mo. The 5-year recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were 77.9%, 83.2%, and 72.7% in primHR-NMIBC, 60.0%, 59%, and 48.9% in recHR-NMIBC, 60.9%, 64.5%, and 54.8% in primMIBC, and 41.3%, 46.5%, and 39% in secMIBC, respectively, with statistically significant differences across all survival outcomes except between recHR-NMIBC and primMIBC. On multivariable Cox regression, recHR-NMIBC was independently associated with shorter RFS (hazard ratio [HR] 1.64; p  = 0.03), CSS (HR 1.79; p  = 0.01), and OS (HR 1.45; p  = 0.03), and secMIBC was associated with shorter CSS (HR 1.77; p  = 0.01) and OS (HR 1.57; p  = 0.006). Limitations include the biases inherent to the retrospective study design., Conclusions: Patients with recHR-NMIBC and primHR-MIBC had similar survival outcomes, while those with sec-MIBC had the worst outcomes. Therefore, early radical intervention may be indicated in selected patients, and potentially neoadjuvant systemic therapies in some patients with recHR-NMIBC., Patient Summary: We compared cancer outcomes in different bladder cancer scenarios in a large, multinational series of patients who underwent removal of the bladder with curative intent. We found that patients who experienced recurrence of non-muscle-invasive bladder cancer (NMIBC) had similar survival outcomes to those with initial muscle-invasive bladder cancer (MIBC), while patients who experienced progression of NMIBC to MIBC had the worst outcomes. Selected patients with non-muscle-invasive disease may benefit from early radical surgery or from perioperative chemotherapy or immunotherapy., (© 2022 The Author(s).)

Single-stranded ends of double-stranded DNA (jagged ends) are more abundant in urinary DNA than in plasma DNA. However, the lengths of jagged ends in urinary DNA remained undetermined, as a previous method used for urinary DNA jagged end sequencing analysis (Jag-seq) relied on unmethylation at CpG sites, limiting the resolution. Here, we performed high-resolution Jag-seq analysis using methylation at non-CpG cytosine sites, allowing determination of exact length of jagged ends. The urinary DNA bore longer jagged ends (~26-nt) than plasma DNA (~17-nt). The jagged end length distribution displayed 10-nt periodicities in urinary DNA, which were much less observable in plasma DNA. Amplitude of the 10-nt periodicities increased in patients with renal cell carcinoma. Heparin treatment of urine diminished the 10-nt periodicities. The urinary DNA jagged ends often extended into nucleosomal cores, suggesting potential interactions with histones. This study has thus advanced our knowledge of jagged ends in urine DNA., (© 2022. The Author(s).)

Background: With recent technological advancement, new and improved endoscopic instruments and laser devices have catapulted flexible ureteroscopy to the forefront, hence making retrograde intrarenal surgery (RIRS) a popular choice for the management of renal stones. However, RIRS has also resulted in an increasing number of work-related musculoskeletal disorders, which can have a detrimental impact on surgeons' physical health and operative lifespan. The aim of our review is to examine the impact and feasibility of ergonomic adjustments and outline future directions and recommendations to improve the awareness of and reduce the prevalence of musculoskeletal injuries among urologists. Methods: This study was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A thorough literature review was conducted of several databases using the following keywords and Medical Subject Headings (MeSH) terms to generate a search strategy: nephrolithiasis, kidney calculus, renal calculus, staghorn calculus, ergonomics, position, fatigue, comfort, tire, physical strain, visual strain, muscle, ureteroscopy, RIRS, laser, and lithotripsy. Studies were chosen for inclusion by reviewers independently, and the data were consolidated for analysis. Results: A total of 1446 articles were identified on initial literature search; 23 were included in the final analysis. The impact of various ergonomic modifications on operative outcomes, surgeons, surgical equipment, and patients, was analyzed. In addition, we summarized all the improvements that resulted in better ergonomics in RIRS. Conclusion: Ergonomics in RIRS is poorly understood and there are currently no formal guidelines for this aspect. While modern endourology armamentarium seems to help with procedural ergonomics, more needs to be done to enhance surgeon comfort, protect surgeon longevity, and prioritize the health and safety of endourologists.