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Patients with sarcomatoid renal cell carcinoma (sRCC) have a poor prognosis. In the randomised, double-blind phase 3 IMmotion010 trial (NCT03024996), adjuvant atezolizumab did not demonstrate a disease-free survival (DFS) benefit versus placebo in the overall population of patients with locoregional renal cell carcinoma with an increased risk of recurrence following surgery. This prespecified subgroup analysis of efficacy and safety was completed in 104 patients with sRCC. Baseline characteristics were similar between treatment arms. At a median follow-up of 45 mo, the median DFS was not evaluable (NE; 95% confidence interval [CI], 12 mo-NE) in the atezolizumab arm (n = 37) and 23 mo (95% CI, 11-NE) in the placebo arm (n = 66; hazard ratio 0.77 [95% CI, 0.44-1.4]). In the sRCC subgroup, grade 3/4 treatment-related adverse events (TRAEs) occurred in one patient (2.7%) in the atezolizumab arm and two patients (3.0%) in the placebo arm. By comparison, 54 of 353 patients (15%) and 16 of 317 patients (5.0%) with non-sarcomatoid histology reported grade 3/4 TRAEs in the respective arms. In conclusion, the difference in DFS was not statistically significant between adjuvant atezolizumab and placebo in patients with sRCC. The safety profile was similar between patients with sRCC and non-sRCC. PATIENT SUMMARY: Patients with a specific type of locoregional kidney cancer (tumours with sarcomatoid features) were treated with atezolizumab or placebo after surgery. Slightly more patients treated with atezolizumab lived longer without the disease getting worse than those treated with placebo, although this finding was not statistically significant. The side effects were similar to those seen in patients with other types of kidney cancer treated with atezolizumab in the same study (IMmotion010). In patients with sarcomatoid kidney cancer, atezolizumab was tolerable and may be more effective than placebo, but this requires further study., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The purpose was to quantify physical performance in men and women during British Army Junior Entry (Army-JE), British Army Standard Entry (Army-SE) and Royal Air Force (RAF) basic training (BT)., Design: Prospective longitudinal study., Methods: 381 participants ((339 men and 42 women) n=141 Army-JE, n=132 Army-SE, n=108 RAF) completed a 2 km run, medicine ball throw (MBT) and isometric mid-thigh pull (MTP), pre-BT and post-BT. To examine changes in pre-BT to post-BT physical test performance, for each course, paired Student t-test and Wilcoxon test were applied to normally and non-normally distributed data, respectively, with effect sizes reported as Cohen's D and with rank biserial correlations, respectively. A one-way between-subjects analysis of variance (ANOVA) (or Welch ANOVA for non-normally distributed data) compared performance between quartiles based on test performance pre-BT. Where the main tests statistic, p value and effect sizes identified likely effect of quartile, post hoc comparisons were made using Games-Howell tests with Tukey's p value. Data are presented as mean±SD, with statistical significance set at p<0.05., Results: During BT, 2 km run time improved by 13±46 s (-2.1%±8.1%), 30±64 s (-4.8%±12.3%) and 24±27 s (-4.5%±5.1%) for Army-JE, Army-SE and RAF, respectively (all p<0.005). MBT distance increased by 0.27±0.28 m (6.8%±7.0%) for Army-JE (p<0.001) and 0.07±0.46 m (2.3%±10.9%) for Army-SE (p=0.040), but decreased by 0.08±0.27 m (-1.4%±6.0%) for RAF (p=0.002). MTP force increased by 80±281 n (10.8%±27.6%) for Army-JE (p<0.001) and did not change for Army-SE (-36±295 n, -0.7%±20.6%, p=0.144) or RAF (-9±208 n, 1.0±17.0, p=0.603). For all tests and cohorts, participants in the lowest quartile of pre-BT performance scores demonstrated greater improvements, compared with participants in the highest quartile (except Army-JE MBT, ∆% change similar between all quartiles)., Conclusions: Changes in physical performance were observed for the three fitness tests following the different BT courses, and recruits with the lowest strength and aerobic fitness experienced greatest improvements., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: The treatment landscape for metastatic renal cell carcinoma (mRCC) has evolved significantly in recent years, leading to improved outcomes. The aim of this review is to provide clinicians with a practical guide for selecting first- and second-line treatments on the basis of current evidence., Methods: We critically evaluated systemic treatment strategies for mRCC. A comprehensive literature search was conducted in PubMed and Embase, alongside manual searches of guidelines and conference proceedings up to October 2024. A narrative review was performed to reach a consensus, with voting used to resolve differing opinions among authors., Key Findings and Limitations: First-line treatment options include immune checkpoint inhibitor (ICI)-based combinations or tyrosine kinase inhibitors (TKIs). Four combination regimens have been approved internationally. Owing to the lack of head-to-head trials and standardized biomarkers, treatment decisions rely on factors such as International Metastatic RCC Database Consortium (IMDC) risk score, functional status, safety profiles, sarcomatoid features, use of immunosuppressive drugs, and need for immediate response. Despite advances, many patients will experience disease progression on ICI-based therapy, necessitating further treatment. The need for standardized second-line approaches remains unmet. TKIs, alone or with everolimus, show promising efficacy, while HIF2a inhibitors offer newer options with a favorable toxicity profile. Rechallenge with ICIs after early progression is not recommended., Conclusions and Clinical Implications: For optimal mRCC treatment selection, clinicians must carefully balance efficacy, toxicity, and patient preferences, especially when transitioning between first- and second-line therapies, to provide individualized care., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the detection and predictors of prostate cancer (PCA) and clinically significant prostate cancer (csPCA) in patients with positive multiparametric MRI (mpMRI) followed by a negative MRI - guided target biopsy (TB) and systematic biopsy (SB)., Materials and Methods: This retrospective multicenter study included 694 patients from 10 tertiary referral centers with an initial positive mpMRI (PI-RADS ≥ 3) and negative results on both MRI-TB and SB. Patients were classified into three groups based on follow-up: Group 1 (prostate re-biopsy without new mpMRI), Group 2 (standardized second prostate mpMRI and subsequent re-biopsy), and Group 3 (follow-up with mpMRIs and biopsy based on clinical and radiological triggers). The primary outcomes were the detection of any PCA and csPCA during follow up. Study groups were compared according to their probability of PCA and csPCA assessed with the ERSPC-MRI risk calculator. Statistical analysis included Kaplan - Meier analysis, Cox regression, and multivariable analysis for the detection of (cs)PCa., Results: The overall detection of PCA and csPCA was 26.8% and 19.3%, respectively, with varying rates in different PI-RADS groups. Group 3 had the highest 2-year and 5-year PCA-free survival (94 and 84%) and csPCA - free survival (96 and 86%). Multivariable analysis revealed a significantly higher risk of PCA and csPCA in Group 1 and 2 compared to Group 3 (p < 0.01). Clinical and radiological predictors for PCA and csPCA included higher age, prostate volume, PI-RADS score, the presence of atypical small acinar proliferation (ASAP), and a smaller number of TB and SB performed during the initial biopsy. Study limitations, include the retrospective design and reliance on clinical and radiological triggers for follow-up decisions., Conclusions: Patients with positive mpMRI but negative TB and SB results exhibit varying rates of PCA and csPCA depending on the follow up scheme. Tailored follow-up strategies are essential for optimal management in this clinical scenario., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The landscape of the management of renal cell carcinoma has evolved substantially in the last decade, leading to improved survival in localised and advanced disease. We review the epidemiology, pathology, and diagnosis of renal cell carcinoma and discuss the evidence for current management strategies from localised to metastatic disease. Developments in adjuvant therapies are discussed, including use of pembrolizumab-the first therapy to achieve overall survival benefit in the adjuvant setting. The treatment of advanced disease, including landmark trials that have established immune checkpoint inhibition as a standard of care, are also reviewed. We also discuss the current controversies that exist surrounding the management of metastatic renal cell carcinoma, including the use of risk assessment models for disease stratification and treatment selection for frontline therapy. Management of non-clear cell renal cell carcinoma subtypes is also reviewed. Future directions of research, including a discussion of ongoing clinical trials and the need for reliable biomarkers to guide treatment in kidney cancer, are also highlighted., Competing Interests: Declaration of interests No funding or payment has been directed towards this review or the authors' decision to submit for publication. MY has received honoria from Eisai. BS has received reimbursement for travel expenses from Genentech, Merck Sharp & Dohme (MSD), Pfizer, and Bristol-Myers Squibb (BMS); has received research funding from Roche, Genentech, Merck Sharp & Dohme, Pfizer, and Bristol-Myers Squibb; and has received honoraria from Merck, Roche, Pfizer, Ellipses, Ipsen, and Janssen. TP declares grants from or contracts with AstraZeneca, BMS, Exelixis, Ipsen, MSD, Novartis, Pfizer, Seagen, Merck Serono, Astellas, Johnson & Johnson, Eisai, and Roche; TP reports payment or honoraria for lectures, presentations, or speakers' bureaus from AstraZeneca, BMS, Exelixis, Incyte, Ipsen, MSD, Novartis, Pfizer, Seagen, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, and Mash Up; and reports travel support from Roche, Pfizer, MSD, AstraZeneca, and Ipsen. CS declares research funding from AB Science, Aragon Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim España, BMS, Clovis Oncology, Exelixis, Genentech, GlaxoSmithKline, F Hoffmann-La Roche, Novartis, Pfizer, and Sanofi-Aventis; speakers' bureau fees from Astellas Pharma, BMS, F Hoffmann-La Roche, Ipsen, and Pfizer; participation on a data safety monitoring board or advisory board for Astellas Pharma, Bayer, BMS, Eusa Pharma, F Hoffmann-La Roche, Ipsen, MSD, Novartis, Pfizer, and Sanofi-Aventis. AB has received company speaker honoraria from Pfizer; and has participated in trials for Pfizer Europe; has participated in advisory boards for BMS, GlaxoSmithKline, and Novartis; is a consultant for Pfizer and Novartis; and has received grants and research support from Pfizer. All other authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Appendicectomy is a common procedure in children with a low risk of mortality, however, complication rates and risk factors are largely unknown. This study aimed to characterise the incidence and epidemiology of postoperative complications in children undergoing appendicectomy in the UK. This multicentre prospective observational cohort study, which included children aged 1-16 y who underwent surgery for suspected appendicitis, was conducted between November 2019 and January 2022. The primary outcome was 30-day postoperative morbidity. Data collected included: patient characteristics; comorbidities; and physiological status. Multivariable regression analysis was used to identify independent risk factors for poor outcomes. Data from 2799 children recruited from 80 hospitals were analysed, of which 185 (7%) developed postoperative complications. Children from black and 'other' minority ethnic groups were at significantly higher risk of poor outcomes: OR (95%CI) 4.13 (1.87-9.08), p < 0.001 and 2.08 (1.12-3.87), p = 0.021, respectively. This finding was independent of socio-economic status and type of appendicitis found on histology. Other risk factors for complications included: ASA physical status ≥ 3 (OR (95%CI) 4.05 (1.70-9.67), p = 0.002); raised C-reactive protein (OR 95%CI 1.01 (1.00-1.01), p < 0.001); pyrexia (OR (95%CI) 1.77(1.20-2.63), p = 0.004); and peri-operative oxygen supplementation (OR (95%CI) 4.20 (1.44-12.24), p = 0.009). In the UK NHS, which is a universally accessible healthcare system, ethnicity, but not socio-economic status, was associated with an increased risk of postoperative complications in children having surgery for acute appendicitis. Further evaluations and interventions are required to address this health inequality in keeping with NHS and international priorities., (© 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Introduction: Clinical markers of response in metastatic renal cell carcinoma (mRCC) are lacking. Low hemoglobin (Hb) is associated with poor outcomes in the IMDC risk score. This study evaluates the role of Hb as a marker of treatment outcomes in mRCC., Patients and Methods: This multicenter retrospective study evaluated 276 patients with mRCC treated with frontline immune checkpoint inhibitor (ICI) therapy, ICI and vascular endothelial growth factor (VEGF) inhibitor (VEGFI) combinations (ICI/VEGFI), or VEGFI monotherapy between 2014 and 2021. Hb levels at baseline, week 6 and 12 and at disease progression or death were recorded. Patients were categorized as responders (CR+PR) or nonresponders (SD+PD) using cross-sectional imaging at week 12. The association between baseline and dynamic changes in Hb and oncological outcomes was assessed., Results: Thirty-seven percent, 40% and 22% of patients received ICIs, ICI/VEGFI and VEGFI respectively. In patients receiving ICIs, there was a significant increase in Hb amongst responders from baseline to week 12 (P= .02). Amongst patients receiving ICI/VEGFI, there was an increase in Hb from baseline to week 12 which was greater in responders (P< .001). In patients receiving VEGFI monotherapy, responders had a higher Hb at baseline (P= .01), week 6 (P= .04), and week 12 (P= .003). An increase in Hb was a significant independent predictor of progression-free survival amongst patients receiving ICIs (HR 0.40, 95%CI, 0.19-0.83, P= .009)., Conclusion: Baseline and dynamic changes in Hb are associated with first-line treatment outcomes in patients with mRCC and represent a pragmatic early serological marker., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs)., Methods: PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a 'Trial within cohorts' studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician., Trial Registration: Ethical board approval has been obtained (2021&#95;218) and the study has been registered at ClinicalTrials.gov (NCT05326620)., Discussion: PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization., (© 2023. The Author(s).)

Context: Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear., Objective: To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status., Evidence Acquisition: We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers., Evidence Synthesis: A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants., Conclusions: There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results., Patient Summary: In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups., (© 2023 The Author(s).)

Background: Effective adjuvant therapy for patients with resected localised renal cell carcinoma represents an unmet need, with surveillance being the standard of care. We report results from part A of a phase 3, randomised trial that aimed to assess the efficacy and safety of adjuvant nivolumab plus ipilimumab versus placebo., Methods: The double-blind, randomised, phase 3 CheckMate 914 trial enrolled patients with localised clear cell renal cell carcinoma who were at high risk of relapse after radical or partial nephrectomy between 4-12 weeks before random assignment. Part A, reported herein, was done in 145 hospitals and cancer centres across 20 countries. Patients were randomly assigned (1:1) to nivolumab (240 mg) intravenously every 2 weeks for 12 doses plus ipilimumab (1 mg/kg) intravenously every 6 weeks for four doses, or matching placebo, via an interactive response technology system. The expected treatment period was 24 weeks, and treatment could be continued until week 36, allowing for treatment delays. Randomisation was stratified by TNM stage and nephrectomy (partial vs radical). The primary endpoint was disease-free survival according to masked independent central review; safety was a secondary endpoint. Disease-free survival was analysed in all randomly assigned patients (intention-to-treat population); exposure, safety, and tolerability were analysed in all patients who received at least one dose of study drug (all-treated population). This study is registered with ClinicalTrials.gov, NCT03138512., Findings: Between Aug 28, 2017, and March 16, 2021, 816 patients were randomly assigned to receive either adjuvant nivolumab plus ipilimumab (405 patients) or placebo (411 patients). 580 (71%) of 816 patients were male and 236 (29%) patients were female. With a median follow-up of 37·0 months (IQR 31·3-43·7), median disease-free survival was not reached in the nivolumab plus ipilimumab group and was 50·7 months (95% CI 48·1 to not estimable) in the placebo group (hazard ratio 0·92, 95% CI 0·71-1·19; p=0·53). The number of events required for the planned overall survival interim analysis was not reached at the time of the data cutoff, and only 61 events occurred (33 in the nivolumab plus ipilimumab group and 28 in the placebo group). 155 (38%) of 404 patients who received nivolumab plus ipilimumab and 42 (10%) of 407 patients who received placebo had grade 3-5 adverse events. All-cause adverse events of any grade led to discontinuation of nivolumab plus ipilimumab in 129 (32%) of 404 treated patients and of placebo in nine (2%) of 407 treated patients. Four deaths were attributed to treatment with nivolumab plus ipilimumab and no deaths were attributed to treatment with placebo., Interpretation: Adjuvant therapy with nivolumab plus ipilimumab did not improve disease-free survival versus placebo in patients with localised renal cell carcinoma at high risk of recurrence after nephrectomy. Our study results do not support this regimen for the adjuvant treatment of renal cell carcinoma., Funding: Bristol Myers Squibb and Ono Pharmaceutical., Competing Interests: Declaration of interests RJM reports clinical trial support (institutional) from Bristol Myers Squibb (BMS) for this manuscript; advisory board fees from AstraZeneca, AVEO, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly Oncology, Merck, Novartis, and Pfizer; and fees (institutional) for coordinating principal investigator from AVEO, BMS, Eisai, Exelixis, Genentech/Roche, Merck, and Pfizer. VG reports medical writing and processing charges from BMS for this manuscript, research grants (institutional) from BMS, Ipsen, MSD, and Pfizer; speakers' bureau fees from Astellas, AstraZeneca, BMS, Eisai, Ipsen, Janssen-Cilag, Merck Serono, MSD, Nanobiotix, Novartis, Ono Pharmaceutical, Pfizer, and Roche; advisory board fees from Apogepha, BMS, Debiopharm, Eisai, EUSA, MSD, Nanobiotix, Oncorena, PCI Biotech, Pfizer, Roche, and Merck Serono; leadership roles (unpaid) with AIO and Das Lebenshaus for patient advocacy; stock options from AstraZeneca, BMS, MSD, and Seattle Genetics; steering committee membership for BMS, Eisai, Ipsen, and Novartis; and being trial chair for PharmaMar. YT reports research grants from Chugai and Ono Pharmaceutical; speakers' bureau fees from Astellas, BMS, Merck, and Ono Pharmaceutical; and advisory board fees from Eisai, Ono Pharmaceutical, and MSD. SB reports research grants from Novartis; speakers' bureau fees from BMS, Ipsen, MSD, and Novartis; payment for expert testimony from MSD, BMS, Ipsen, and Pfizer; advisory board fees from BMS, Ipsen, MSD, Novartis, and Pfizer; fees (institutional) for being a coordinating principal investigator from BMS and Ipsen; and being a member of AIOM and Meet-URO group. PB reports research grants from BMS, Ipsen, MSD, Pfizer, Merck, AstraZeneca, and Janssen-Cilag; consulting fees from BMS, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Amgen, and Gilead; honoraria from BMS, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Seagen, Novartis, and AAA; travel expense support from Pfizer, Merck, BMS, and Ipsen; and advisory board fees from Merck and Pfizer. JCG reports medical writing support from BMS for this manuscript; research grants (institutional) from BeiGene; honoraria from MSD and GlaxoSmithKline; travel expense support from AstraZeneca; advisory board fees from BMS, GlaxoSmithKline, MSD, Eisai, Janssen, and AstraZeneca; stock options from ICON Cancer Centres; meeting chair fees from Ipsen; and local principal investigator fees from BMS. J-BL reports consulting fees from BMS, Merck, Sanofi, Paladin, Pfizer, Novartis, Knights Pharmacy, Verity, and AbbVie; speakers' bureau fees from Tersera and Tolmar; advisory board fees from BMS, Knights Pharmacy, and Verity; being a local principal investigator for BMS; and being a member of AUA, Canadian Uro-Oncology Group, and Canadian Urological Association. LA reports research grants (institutional) from BMS, consulting fees (institutional) from BMS, Ipsen, Roche, Novartis, Pfizer, Astellas Pharma, Merck, MSD, AstraZeneca, Janssen, and Eisai; and travel support from BMS and MSD. SG reports advisory board fees from AVEO, Bayer, BMS, Corvus, Eisai, EMD Serono, Exelixis, Merck, Pfizer, QED Therapeutics, Sanofi/Genzyme, and Seattle Genetics; and non-financial interests from Agensys, Aravive, AVEO, Bayer, BMS, Calithera, Corvus, Eisai, Exelixis, Gilead, Merck, Novartis, Pfizer, Seattle Genetics, and Surface Oncology. BSh reports research grants (institutional) from Allogene and Rebiotix; royalties from Up to Date; consulting fees from Veracyte and Merck; speakers' bureau fees from Merck; advisory board fees from Genentech, Merck, and Johnson & Johnson; and board leadership fees from the National Cancer Institute PDQ. JSo reports consulting fees from Apexigen, Jazz Pharmaceuticals, and Iovance Biotherapeutics; and honoraria from Apexigen, Jazz Pharmaceuticals, and Iovance Biotherapeutics. MS reports support from BMS for this manuscript; grants from Pfizer, GlaxoSmithKline, AVEO, BMS, Novartis, Bayer, Roche/Genentech, Immatics, Wilex, Ipsen, Exelixis, and Eisai; consulting fees from Pfizer, GlaxoSmithKline, Novartis, Bayer, Roche AVEO, EUSA Pharma, Astellas, Ipsen, Exelixis, Peloton Therapeutics, Eisai, BMS, MSD, and Apogepha; and travel support from Pfizer, EUSA Pharma, Ipsen, Eisai, BMS, MSD, and Apogepha. BSi, JSp, and AC are employed by and have stock ownership in BMS. AB reports research grants from Pfizer, advisory board fees from the International Kidney Cancer Coalition and the Kidney Cancer Association; and being a local principal investigator and steering committee member for BMS and Roche/Genentech. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To analyse variation in clinical management of cT1 renal cell carcinoma (RCC) in the Netherlands related to surgical hospital volume (HV)., Materials and Methods: Patients diagnosed with cT1 RCC during 2014-2020 were identified in the Netherlands Cancer Registry. Patient and tumour characteristics were retrieved. Hospitals performing kidney cancer surgery were categorised by annual HV as low (HV < 25), medium (HV = 25-49) and high (HV > 50). Trends over time in nephron-sparing strategies for cT1a and cT1b were evaluated. Patient, tumour and treatment characteristics of (partial) nephrectomies were compared by HV. Variation in applied treatment was studied by HV., Results: Between 2014 and 2020, 10 964 patients were diagnosed with cT1 RCC. Over time, a clear increase in nephron-sparing management was observed. The majority of cT1a underwent a partial nephrectomy (PN), although less PNs were applied over time (from 48% in 2014 to 41% in 2020). Active surveillance (AS) was increasingly applied (from 18% to 32%). For cT1a, 85% received nephron-sparing management in all HV categories, either with AS, PN or focal therapy (FT). For T1b, radical nephrectomy (RN) remained the most common treatment (from 57% to 50%). Patients in high-volume hospitals underwent more often PN (35%) for T1b compared with medium HV (28%) and low HV (19%)., Conclusion: HV is related to variation in the management of cT1 RCC in the Netherlands. The EAU guidelines have recommended PN as preferred treatment for cT1 RCC. In most patients with cT1a, nephron-sparing management was applied in all HV categories, although differences in applied strategy were found and PN was more frequently used in high HV. For T1b, high HV was associated with less appliance of RN, whereas PN was increasingly used. Therefore, closer guideline adherence was found in high-volume hospitals., Competing Interests: A. Bex: Recipient of a restricted educational grant from Pfizer for a neoadjuvant trial (remuneration made to the employer and sponsor of the trial). Steering committee member of adjuvant trials of BMS and Roche/Genentech. No other conflicts of interest to declare by the authors., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

This work describes the development of a new approach to measure drug levels and lipid fingerprints in single living mammalian cells. Nanocapillary sampling is an approach that enables the selection and isolation of single living cells under microscope observation. Here, live single cell nanocapillary sampling is coupled to liquid chromatography for the first time. This allows molecular species to be separated prior to ionisation and improves measurement precision of drug analytes. The efficiency of transferring analytes from the sampling capillary into a vial was optimised in this work. The analysis was carried out using standard flow liquid chromatography coupled to widely available mass spectrometry instrumentation, highlighting opportunities for widespread adoption. The method was applied to 30 living cells, revealing cell-to-cell heterogeneity in the uptake of different drug molecules. Using this system, we detected 14-158 lipid features per single cell, revealing the association between bedaquiline uptake and lipid fingerprints.

Introduction: Thirty four per cent of women use hormonal contraceptives in the UK and the contraceptive pill is the most common method. There are no comparable data in the UK Armed Forces, but servicewomen are often required to complete physically arduous job roles in combat zones and may be more likely to take contraceptives to control or stop menstrual bleeding than the general population. We explored the prevalence of hormonal contraceptive prescriptions in the UK Armed Forces., Methods: The study used defence medical records (Defence Medical Information Capability Programme) to identify hormonal contraceptive prescriptions for all serving regular UK servicewomen (n=15 738) as of 1 September 2017., Results: Thirty one per cent of servicewomen (Royal Navy, 28%; British Army, 30%; Royal Air Force, 34%) had a current prescription for a hormonal contraceptive. Non-officer ranks were more likely to have a prescription for a hormonal contraceptive (32%) than officers (27%) (p<0.01). The contraceptive pill was more commonly prescribed (68%) than long-acting reversible contraceptive methods (32%) (contraceptive injection, 11%; contraceptive implant, 11%; intrauterine device, 10%)., Conclusion: Prescription data suggest that the prevalence of hormonal contraceptive use in UK servicewomen is comparable with the general UK population. These findings suggest that military service does not influence prevalence or choice of hormonal contraceptives., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Brain tumours lead to significant morbidity including a neurocognitive, physical and psychological burden of disease. The extent to which they impact the multiple domains of health is difficult to capture leading to a significant degree of unmet needs. Mobile health tools such as Vinehealth have the potential to identify and address these needs through real-world data generation and delivery of personalised educational material and therapies. We aimed to establish the feasibility of Vinehealth integration into brain tumour care, its ability to collect real-world and (electronic) patient-recorded outcome (ePRO) data, and subjective improvement in care., Design: A mixed-methodology IDEAL stage 1 study., Setting: A single tertiary care centre., Participants: Six patients consented and four downloaded and engaged with the mHealth application throughout the 12 weeks of the study., Main Outcome Measures: Over a 12-week period, we collected real-world and ePRO data via Vinehealth. We assessed qualitative feedback from mixed-methodology surveys and semistructured interviews at recruitment and after 2 weeks., Results: 565 data points were captured including, but not limited to: symptoms, activity, well-being and medication. EORTC QLQ-BN20 and EQ-5D-5L completion rates (54% and 46%) were impacted by technical issues; 100% completion rates were seen when ePROs were received. More brain cancer tumour-specific content was requested. All participants recommended the application and felt it improved care., Conclusions: Our findings indicate value in an application to holistically support patients living with brain cancer tumours and established the feasibility and safety of further studies to more rigorously assess this., Competing Interests: Competing interests: GK, RP and RM are/were all employees of Vinehealth throughout the duration of the study. No other conflicts of interest declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Over 1.5 million major surgical procedures take place in the UK NHS each year and approximately 25% of patients develop at least one complication. The most widely used risk-adjustment model for postoperative morbidity in the UK is the physiological and operative severity score for the enumeration of mortality and morbidity. However, this model was derived more than 30 years ago and now overestimates the risk of morbidity. In addition, contemporary definitions of some model predictors are markedly different compared with when the tool was developed. A second model used in clinical practice is the American College of Surgeons National Surgical Quality Improvement Programme risk model; this provides a risk estimate for a range of postoperative complications. This model, widely used in North America, is not open source and therefore cannot be applied to patient populations in other settings. Data from a prospective multicentre clinical dataset of 118 NHS hospitals (the peri-operative quality improvement programme) were used to develop a bespoke risk-adjustment model for postoperative morbidity. Patients aged ≥ 18 years who underwent colorectal surgery were eligible for inclusion. Postoperative morbidity was defined using the postoperative morbidity survey at postoperative day 7. Thirty-one candidate variables were considered for inclusion in the model. Death or morbidity occurred by postoperative day 7 in 3098 out of 11,646 patients (26.6%). Twelve variables were incorporated into the final model, including (among others): Rockwood clinical frailty scale; body mass index; and index of multiple deprivation quintile. The C-statistic was 0.672 (95%CI 0.660-0.684), with a bootstrap optimism corrected C-statistic of 0.666 at internal validation. The model demonstrated good calibration across the range of morbidity estimates with a mean slope gradient of predicted risk of 0.959 (95%CI 0.894-1.024) with an index-corrected intercept of -0.038 (95%CI -0.112-0.036) at internal validation. Our model provides parsimonious case-mix adjustment to quantify risk of morbidity on postoperative day 7 for a UK population of patients undergoing major colorectal surgery. Despite the C-statistic of &lt; 0.7, our model outperformed existing risk-models in widespread use. We therefore recommend application in case-mix adjustment, where incorporation into a continuous monitoring tool such as the variable life adjusted display or exponentially-weighted moving average-chart could support high-level monitoring and quality improvement of risk-adjusted outcome at the population level., (© 2022 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Targeted bisulfite sequencing (TBS) has become the method of choice for the cost-effective, targeted analysis of the human methylome at base-pair resolution. In this study, we benchmarked five commercially available TBS platforms-three hybridization capture-based (Agilent, Roche and Illumina) and two reduced-representation-based (Diagenode and NuGen)-across 11 samples. Two samples were also compared with whole-genome DNA methylation sequencing with the Illumina and Oxford Nanopore platforms. We assessed workflow complexity, on/off-target performance, coverage, accuracy and reproducibility. Although all platforms produced robust and reproducible data, major differences in the number and identity of the CpG sites covered make it difficult to compare datasets generated on different platforms. To overcome this limitation, we applied imputation and show that it improves interoperability from an average of 10.35% (0.8 million) to 97% (7.6 million) common CpG sites. Our study provides guidance on which TBS platform to use for different methylome features and offers an imputation-based harmonization solution that allows comparative, integrative analysis., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The standard of care for locoregional renal cell carcinoma is surgery, but many patients experience recurrence. The objective of the current study was to determine if adjuvant atezolizumab (vs placebo) delayed recurrence in patients with an increased risk of recurrence after resection., Methods: IMmotion010 is a randomised, double-blind, multicentre, phase 3 trial conducted in 215 centres in 28 countries. Eligible patients were patients aged 18 years or older with renal cell carcinoma with a clear cell or sarcomatoid component and increased risk of recurrence. After nephrectomy with or without metastasectomy, patients were randomly assigned (1:1) to receive atezolizumab (1200 mg) or placebo (both intravenous) once every 3 weeks for 16 cycles or 1 year. Randomisation was done with an interactive voice-web response system. Stratification factors were disease stage (T2 or T3a vs T3b-c or T4 or N+ vs M1 no evidence of disease), geographical region (north America [excluding Mexico] vs rest of the world), and PD-L1 status on tumour-infiltrating immune cells (<1% vs ≥1% expression). The primary endpoint was investigator-assessed disease-free survival in the intention-to-treat population, defined as all patients who were randomised, regardless of whether study treatment was received. The safety-evaluable population included all patients randomly assigned to treatment who received any amount of study drug (ie, atezolizumab or placebo), regardless of whether a full or partial dose was received. This trial is registered with ClinicalTrials.gov, NCT03024996, and is closed to further accrual., Findings: Between Jan 3, 2017, and Feb 15, 2019, 778 patients were enrolled; 390 (50%) were assigned to the atezolizumab group and 388 (50%) to the placebo group. At data cutoff (May 3, 2022), the median follow-up duration was 44·7 months (IQR 39·1-51·0). Median investigator-assessed disease-free survival was 57·2 months (95% CI 44·6 to not evaluable) with atezolizumab and 49·5 months (47·4 to not evaluable) with placebo (hazard ratio 0·93, 95% CI 0·75-1·15, p=0·50). The most common grade 3-4 adverse events were hypertension (seven [2%] patients who received atezolizumab vs 15 [4%] patients who received placebo), hyperglycaemia (ten [3%] vs six [2%]), and diarrhoea (two [1%] vs seven [2%]). 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo had a serious adverse event. There were no treatment-related deaths., Interpretation: Atezolizumab as adjuvant therapy after resection for patients with renal cell carcinoma with increased risk of recurrence showed no evidence of improved clinical outcomes versus placebo. These study results do not support adjuvant atezolizumab for treatment of renal cell carcinoma., Funding: F Hoffmann-La Roche and Genentech, a member of the Roche group., Competing Interests: Declaration of interests SKP reports advisory or consulting fees from Pfizer, Novartis, Aveo, Myriad Pharmaceuticals, Genentech, Exelixis, Bristol Myers Squibb, Astellas Pharma, Ipsen, and Eisai; and travel support from CRISPR Therapeutics and Roche. RU reports receiving advisory or consulting fees from Pfizer, Merck, and Haymarket Media. JAK reports research grants or funding paid to their institution from Roche/Genentech, Mirati, Merck, and Elypta; consulting fees from Pfizer, Merck, Roche or Genentech, and Johnson & Johnson; participation on a data safety monitoring board or advisory board for Pfizer; and stock ownership or stock options in MedTek and ROM Technologies. VAM reports advisory or consulting fees from Pfizer, Merck, Bristol Myers Squibb, and Ethicon; and participation on a data safety monitoring board or advisory board for Pfizer, Merk, Bristol Myers Squibb, and Ethicon. CS reports grants from Roche; advisory or consulting fees from Bristol Myers Squibb, Ipsen, Astella, Sanofi, Bayer, Merck Sharp, Dohme, and Pfizer; and support for travel from Bristol Myers Squibb, Roche, and Pfizer. LA reports research grants or funding paid to their institution from Bristol Myers Squibb; consulting fees paid to their institution from Astellas, AstraZeneca, Bristol Myers Squibb, Ipsen, Janssen, Merck, Merck Sharpe & Dohme, Novartis, Pfizer, and EISAI; and payment or honoraria paid to their institution from Astella, Bristol Myers Squibb, Ipsen, and Merck Sharpe & Dohme. BR reports payment of grants or contracts to their institution from Pfizer, Roche, Incyte, AstraZeneca, Seattle Genetics, Arrowhead Pharmaceuticals, Immunomedics, Bristol Myers Squibb, Mirati Therapeutics, Merck, Surface Oncology, Aravive, Exelixis, Janssen, Pionyr, and Genentech/Roche; advisory or consulting fees from Bristol Myers Squibb, Pfizer, Genentech/Roche, Aveo, Synthorx, Merck, Corvus, Surface Oncology, Aravive, Alkermes, Arrowhead, Shionogi, Eisai, Nikang Therapeutics, EUSA, Athenex, Allogene Therapeutics, and Debiopharm; travel support from Merck and Bristol Myers Squibb; and stock ownership or stock options in PTC Therapeutics. YT reports research funding from Astellas Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, and Takeda; and payment or honoraria from Astella, Bristol Myers Squibb, Chugai Pharmaceuticals, Novartis, and Ono Pharmaceutical. AGK reports advisory or consulting fees from Janssen, Zodiac, and Pfizer; and travel support from Janssen, Ipsen, and AstraZeneca. GP reports payment or honoraria from AstraZeneca, Bayer, BMS, Eisai, Janssen, Ipsen, Merck, Merck Sharpe & Dohme, Novartis, Pfizer, and Roche; and travel support from Ipsen and Janssen. MZ reports grants from Bristol Myers Squibb and Exelixis; and advisory or consulting fees from Pfizer, EMD Serono, Exelixis, Janssen, and Blue Earth. MH, BC, WL, and SD are employees of Genentech, and report stock ownership or stock options. DB is an employee of F Hoffmann-La Roche. OK is an employee of F Hoffmann-La Roche, and reports stock ownership or stock options. AB reports a restricted research grant payment to their institution from Pfizer; payment to their institution for attending steering committee meetings from Roche/Genentech; and payment to their institution for participation on the data safety monitoring board of Merck Sharpe & Dohme. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC., Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC., Evidence Acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines., Evidence Synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence., Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022., Patient Summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To systematically review the published literature on surgical margins as a risk factor for local recurrence (LR) in patients undergoing partial nephrectomy (PN) for pT1 renal cell carcinomas (RCC)., Evidence Acquisition: A systematic literature search of relevant databases (MEDLINE, Embase and the Cochrane Library) was performed according to the PRISMA criteria up to February 2022. The hypothesis was developed using the PPO method (Patients = patients with pT1 RCC undergoing PN, Prognostic factor = positive surgical margins (PSM) detected on final pathology versus negative surgical margins (NSM) and Outcome = LR diagnosed on follow-up imaging). The primary outcome was the rate of PSM and LR. The risk of bias was assessed by the QUIPS tool., Evidence Synthesis: After assessing 1525 abstracts and 409 full-text articles, eight studies met the inclusion criteria. The percentage of PSM ranged between 0 and 34.3%. In these patients with PSM, LR varied between 0 and 9.1%, whereas only 0-1.5% of LR were found in the NSM-group. The calculated odds ratio (95% confident intervals) varied between 0.04 [0.00-0.79] and 0.27 [0.01-4.76] and was statistically significant in two studies (0.14 [0.02-0.80] and 0.04 [0.00-0.79]). The quality analysis of the included studies resulted in an overall intermediate to high risk of bias and the level of evidence was overall very low. A meta-analysis was considered unsuitable due to the high heterogeneity between the included studies., Conclusion: PSM after PN in patients with pT1 RCC is associated with a higher risk of LR. However, the evidence has significant limitations and caution should be taken with the interpretation of this data., (© 2022. The Author(s).)

Objective: To analyse if exposure to sunitinib in the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial, which investigated opposite sequences of cytoreductive nephrectomy (CN) and systemic therapy, is associated with the overall survival (OS) benefit observed in the deferred CN arm., Patients and Methods: A post hoc analysis of SURTIME trial data. Variables analysed included number of patients receiving sunitinib, time from randomisation to start sunitinib, overall response rate by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, and duration of drug exposure and dose in the intention-to-treat population of the immediate and deferred arm. Descriptive methods and 95% confidence-intervals (CI) were used., Results: In the deferred arm, 97.7% (95% CI 89.3-99.6%; n = 48) received sunitinib vs 80% (95% CI 66.9-88.7%, n = 40) in the immediate arm. Following immediate CN, 19.6% progressed 4 weeks after CN and the median time to start sunitinib was 39.5 vs 4.5 days in the deferred arm. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm vs 32.7% in the deferred arm. Sunitinib dose reductions, escalations and interruptions were not statistically significantly different between arms. Among patients who received sunitinib in the immediate or deferred arm the median total sunitinib treatment duration was 172.5 vs 248 days. Reduction of target lesions was more profound in the deferred arm., Conclusions: In comparison to the deferred CN approach, immediate CN impairs administration, onset, and duration of sunitinib. Starting with systemic therapy leads to early and more profound disease control and identification of progression prior to planned CN, which may have contributed to the observed OS benefit., (© 2021 The Authors BJU International © 2021 BJU International.)

Introduction: A penile prosthesis (PP) may be inserted for erectile dysfunction (ED) and/or urinary management in men with spinal cord injury (SCI). This group of patients is considered high risk for complications due to their reduced mobility and sensation., Objectives: To identify the complication and satisfaction rates following PP insertion in patients with SCI., Methods: A systematic review of the literature was performed according to the PRISMA checklist. The Medline/PubMed and EMBASE databases were searched up to July 27th 2021. Studies on men ≥18 years who had a PP inserted for ED secondary to SCI were included. Two reviewers independently screened all articles, assessed for risk of bias and performed data extraction., Results: Eleven studies including 475 men with SCI were included for analysis. The overall complication rate was 4.2-61.1%. Specific complications included infection, 0-16%; erosion, 3.7-11.1% and mechanical failure, 0-16.7%. The explantation rate was 2.1-16.7% and the revision rate was 2.7-44.4%. Overall, 79.2-92.9% of men were satisfied with their PP and, 36-86.1% were having satisfactory sexual intercourse. In those who used the PP for urinary management ± ED, 86.5--92.8%% were satisfied. Men with SCI had higher rates of complications compared to those without SCI (infection, 2.1-9.1% vs non-SCI, 0.8-5.7%; erosion, 2.1-8.3% vs non-SCI, 0%; explanation, 2.1-8.3% vs non-SCI, 0.8-5.7%)., Conclusion: PP is an option for SCI patients for the management of end-stage ED or urinary function, but the rate of infection, erosion and implant explantation is higher compared with men without SCI. Inflatable penile prosthesis (IPP) is the preferred PP due to the lower risk of erosion, however, they are prone to mechanical failure and require good hand dexterity. A thorough pre-operative counselling is essential. Pang KH, Muneer A, Alnajjar HM, et al. A Systematic Review of Penile Prosthesis Insertion in Patients With Spinal Cord Injury. Sex Med Rev 2022;10:461-470., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

To assess the impact of body mass index (BMI) on peri-operative outcomes of kidney and upper tract robot-assisted surgery. Medical audit of patients who underwent robot-assisted kidney and upper tract cancer surgery at a single institution between 2017 and 2019, categorized on BMI into obese patients with a BMI ≥ 30 kg/m 2 and a control group with BMI < 25 kg/m 2 . Patient and tumour characteristics, surgery time, intraoperative blood loss, intraoperative adverse events (AE) according to the European Association of Urology Intraoperative Adverse Incidents Classification (EAUiaiC), conversion- to-open/radical rate as well as 30-day postoperative AE according to Clavien-Dindo (CD) and length of inpatient stay were analyzed. 366 patients were identified, 141 with a BMI < 25 (normal-weight) and 225 BMI ≥ 30 (obesity). There were no significant differences between the groups in terms of age, gender, comorbidities, tumour size, TNM stage and type of surgery. Obese patients had a higher estimated blood loss (198.05 ml), surgery time (171.75 min), intraoperative AE (all grades) (14.67%, 95% CI (0.10-0.19) as well as adherent perinephric fat (APF) (14.22%, 95% CI (0.09-0.19)) in contrast to the control group (86.85 ml, 148.29 min, 7.04% and 2.12%, respectively). Hospital stay, major intraoperative AE (≥ 3) and major postoperative AE (CD > 2) distributed equally between groups. Robotic kidney and upper tract surgery in obese patients showed an increase in surgery time and blood loss potentially related to APF. However, obesity was not associated with conversion to open surgery or radical nephrectomy in nephron-sparing procedures, length of stay, major intraoperative AE or postoperative complications., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: There is variation in care quality and outcomes for children undergoing emergency abdominal surgery, such as appedectomy. Addressing this requires paediatric-specific quality metrics. The aim of this study was to identify perioperative structure and process measures that are associated with improved outcomes for these children., Methods: We performed a systematic review searching MEDLINE, Embase, CINAHL, Cochrane Library, and Google Scholar for articles published between January 1, 1980 and September 29, 2020 about the perioperative care of children undergoing emergency abdominal surgery. We also conducted secondary searching of references and citations, and we included international professional publications., Results: We identified and analysed 383 peer-reviewed articles and 18 grey literature publications. High-grade evidence pertaining to the perioperative care of this patient group is limited. Most of the evidence available relates to improving diagnostic accuracy using preoperative blood testing, imaging, and clinical decision tools. Processes associated with clinical outcomes include time lapse between time of presentation or initial assessment and surgery, and the use of particular analgesia and antibiotic protocols. Structural factors identified include hospital and surgeon caseload and the use of perioperative care pathways., Conclusions: This review summarises the structural and process measures associated with outcome in paediatric emergency abdominal surgery. Such measures provide a means of evaluating care and identifying areas of practice that require quality improvement, especially in children with appendicitis., Clinical Trial Registration: PROSPERO CRD42017055285., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. PATIENT SUMMARY: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Following CARMENA and SURTIME, patients with metastatic renal cell carcinoma (mRCC) and International Metastatic RCC Database Consortium (IMDC) intermediate and poor risk receive systemic therapy with the primary tumour (primary) in place, with the option of deferred cytoreductive nephrectomy (CN) in responding patients. We retrospectively analysed the safety and efficacy of first-line nivolumab/ipilimumab in 71 primary mRCC patients (42.3% IMDC poor risk; 43.6% with more than three metastatic sites). The baseline mean primary diameter was 9.3 cm and median follow-up was 11.5 mo. Of 69 patients with at least one follow-up computed tomography scan, 23 (33.3 %) had a partial response (PR) of the primary after a median of 4.8 mo, which was associated with a 91.3% overall response rate at metastatic sites (MSs) and absence of progressive disease, irrespective of the IMDC risk. The complete response (CR) rate at MSs ( n  = 7 [10.1%]) is similar to the CR rate in CheckMate 214. Thirteen deferred CNs were performed (18.8%) after a median of 13 mo, rendering four patients disease free. Only 4.3% of primaries progressed; grade 3-4 immune-related adverse events occurred in 31.9%. Irrespective of the IMDC risk, patients with a PR in the primary had a 1-yr overall survival rate of 89% versus 67% in those without ( p  = 0.012)., Patient Summary: Patients with metastatic kidney cancer receiving immunotherapy with nivolumab and ipilimumab had superior response at metastatic sites and better survival irrespective of International Metastatic RCC Database Consortium (IMDC) risk., (© 2021 The Authors.)

The increasing incidence of antimicrobial resistance (AMR) presents a global crisis to healthcare, with longstanding antimicrobial agents becoming less effective at treating and preventing infection. In the surgical setting, antibiotic prophylaxis has long been established as routine standard of care to prevent surgical site infection (SSI), which remains one of the most common hospital-acquired infections. The growing incidence of AMR increases the risk of SSI complicated with resistant bacteria, resulting in poorer surgical outcomes (prolonged hospitalisation, extended durations of antibiotic therapy, higher rates of surgical revision and mortality). Despite these increasing challenges, more data are required on approaches at the institutional and patient level to optimise surgical antibiotic prophylaxis in the era of antibiotic resistance (AR). This review provides an overview of the common resistant bacteria encountered in the surgical setting and covers wider considerations for practice to optimise surgical antibiotic prophylaxis in the perioperative setting., Competing Interests: Dr Esmita Charani reports personal fees from Pfizer, outside the submitted work. Dr Andrew JM Leather reports grants from Economic and Social Research Council (ESRC). The authors report no other conflicts of interest in this work., (© 2021 Menz et al.)

Objective: To analyse the impact of the COVID-19 pandemic on a centralized specialist kidney cancer care pathway., Materials and Methods: We conducted a retrospective analysis of patient and pathway characteristics including prioritization strategies at the Specialist Centre for Kidney Cancer located at the Royal Free London NHS Foundation Trust (RFH) before and during the surge of COVID-19., Results: On 18 March 2020 all elective surgery was halted at RFH to redeploy resources and staff for the COVID-19 surge. Prioritizing of patients according to European Association of Urology guidance was introduced. Clinics and the specialist multidisciplinary team (SMDT) meetings were maintained with physical distancing, kidney surgery was moved to a COVID-protected site, and infection prevention measurements were enforced. During the 7 weeks of lockdown (23 March to 10 May 2020), 234 cases were discussed at the SMDT meetings, 53% compared to the 446 cases discussed in the 7 weeks pre-lockdown. The reduction in referrals was more pronounced for small and asymptomatic renal masses. Of 62 low-priority cancer patients, 27 (43.5%) were deferred. Only one (4%) COVID-19 infection occurred postoperatively, and the patient made a full recovery. No increase in clinical or pathological upstaging could be detected in patients who underwent deferred surgery compared to pre-COVID practice., Conclusion: The first surge of the COVID-19 pandemic severely impacted diagnosis, referral and treatment of kidney cancer at a tertiary referral centre. With a policy of prioritization and COVID-protected pathways, capacity for time-sensitive oncological interventions was maintained and no immediate clinical harm was observed., (© 2021 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

This case presents a 68-yr-old female patient with primary metastatic nonclear renal cell carcinoma (RCC) with multiple bone lesions. The patient underwent a single resection of skull bone lesion (diagnostic for poorly differentiated carcinoma of unknown origin) and cytoreductive nephrectomy. The pathology of the kidney specimen demonstrated an oncocytic papillary RCC. Within 3 mo, she developed skeletal progressive disease and was started on systemic therapy (sunitinib). After initial stabilization, bone metastasis progressed during the third cycle of sunitinib and required second-line therapy (cabozantinib). One of the major unmet needs in non-clear cell RCC is the lack of specific systemic therapy. Data on immunotherapy are still limited. Inclusion of these patients in clinical trials is strongly recommended. PATIENT SUMMARY: Patients with metastatic kidney cancer who present with the less common histological subtype (non-clear cell) have poor survival. In this case, the patient responded to second-line therapy. Very few therapies provide response to treatment. Patients should be offered participation in clinical trials testing combinations with immunotherapy., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Radiomics is a specific field of medical research that uses programmable recognition tools to extract objective information from standard images to combine with clinical data, with the aim of improving diagnostic, prognostic, and predictive accuracy beyond standard visual interpretation. We performed a narrative review of radiomic applications that may support improved characterization of small renal masses (SRM). The main focus of the review was to identify and discuss methods which may accurately differentiate benign from malignant renal masses, specifically between renal cell carcinoma (RCC) subtypes and from angiomyolipoma without visible fat (fat-poor AML) and oncocytoma. Furthermore, prediction of grade, sarcomatoid features, and gene mutations would be of importance in terms of potential clinical utility in prognostic stratification and selecting personalised patient management strategies., Methods: A detailed search of original articles was performed using the PubMed-MEDLINE database until 20 September 2020 to identify the English literature relevant to radiomics applications in renal tumour assessment. In total, 42 articles were included in the analysis in 3 main categories related to SRM: prediction of benign versus malignant SRM, subtypes, and nuclear grade, and other features of aggressiveness., Conclusion: Overall, studies reported the superiority of radiomics over expert radiological assessment, but were mainly of retrospective design and therefore of low-quality evidence. However, it is clear that radiomics is an attractive modality that has the potential to improve the non-invasive diagnostic accuracy of SRM imaging and prediction of its natural behaviour. Further prospective validation studies of radiomics are needed to augment management algorithms of SRM., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Tissue engineering is an evolving multi-disciplinary field with cutting-edge technologies and innovative scientific perceptions that promise functional regeneration of damaged tissues/organs. Tissue engineered medical products (TEMPs) are biomaterial-cell products or a cell-drug combination which is injected, implanted or topically applied in the course of a therapeutic or diagnostic procedure. Current tissue engineering strategies aim at 3D printing/bioprinting that uses cells and polymers to construct living tissues/organs in a layer-by-layer fashion with high 3D precision. However, unlike conventional drugs or therapeutics, TEMPs and 3D bioprinted tissues are novel therapeutics and need different regulatory protocols for clinical trials and commercialization processes. Therefore, it is essential to understand the complexity of raw materials, cellular components, and manufacturing procedures to establish standards that can help to translate these products from bench to bedside. These complexities are reflected in the regulations and standards that are globally in practice to prevent any compromise or undue risks to patients. This review comprehensively describes the current legislations, standards for TEMPs with a special emphasis on 3D bioprinted tissues. Based on these overviews, challenges in the clinical translation of TEMPs & 3D bioprinted tissues/organs along with their ethical concerns and future perspectives are discussed., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Purpose of Review: To give an overview of the significance as well as recent developments in antibiotic stewardship (ABS) in urology and for the treatment of urinary tract infections (UTI). This rapid review is focused on recent publications during the past 18 months., Recent Findings: Despite the evidence to support the use of ABS interventions in the treatment of UTIs, there remains considerable inappropriate use of antibiotics, up to 68%, especially concerning the treatment of asymptomatic bacteriuria and the overuse of fluoroquinolones. Emerging evidence indicate that ABS programs can improve patient outcome and reduce multidrug-resistant pathogens.Interestingly, in this past 18 months new targets for ABS have been developed, e.g. involvement of a pharmacist, strict adherence to guidelines, improvement of the guidelines itself and understanding the prescription process in the emergency room as well as the analysis of own surveillance data., Summary: ABS programs in urology are essential and their significance has become more apparent than ever before. New targets for ABS interventions should be evaluated in prospective controlled clinical trials of their effectiveness to reduce further inappropriate antibiotic use without hindering the treatment of UTIs., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Context: The epidemiological signature of renal cell carcinoma (RCC) during the past decades is explained by overdetection and overtreatment of indolent cancers; furthermore, a non-negligible proportion of patients undergoing surgery for suspected RCC harbour benign renal tumours. As the gold standard for RCC diagnosis remains histopathological analysis of surgical or biopsy specimens, implementation of noninvasive diagnostic strategies to discriminate between benign and malignant renal masses is an urgent unmet need., Objective: To systematically review novel liquid biomarkers and imaging modalities for RCC diagnosis., Evidence Acquisition: A systematic review of the recent English-language literature was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42020190773) using the MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov databases. Risk-of-bias assessment was performed according to the QUADAS 2 tool., Evidence Synthesis: Overall, 15 studies (six on biomarkers and nine on imaging) and eight clinical trials were included. None of the biomarkers or imaging modalities has been validated or shown to have a distinct clinical value for RCC. Specific combinations of urinary cell-free and exosomal miRNAs, urinary miR-15a, and specific panels of urinary metabolites assessed by metabolomics appear promising. In addition, machine/deep learning algorithms and radiomics applied to cross-sectional images may have potential to improve RCC diagnosis. Most studies are limited by the retrospective design, size, and lack of external validation., Conclusions: Liquid biomarkers or imaging modalities are not ready for integration in the clinic and further well-designed studies must validate preliminary findings and explore utility in clinical decision-making., Patient Summary: We provide a comprehensive overview of the currently available biomarkers (measured in blood or urine) and novel imaging tests (other than conventional imaging) to discriminate kidney cancer from benign renal masses in a noninvasive fashion. None of the biomarkers or imaging modalities studied was validated or added clinical value; therefore, none of them can be implemented in the clinic. However, these approaches appear to be promising for improving the diagnosis of kidney cancer in the future., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel performed a protocol-driven systematic review (SR) on thermal ablation (TA) compared with partial nephrectomy (PN) for T1N0M0 renal masses, in order to provide evidence to support its recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed, and only comparative studies published between 2000 and 2019 were included. Twenty-six nonrandomised comparative studies were included, recruiting a total of 167 80 patients. Risk of bias (RoB) assessment revealed high or uncertain RoB across all studies, with the vast majority being retrospective, observational studies with poorly matched controls and short follow-up. Limited data showed TA to be safe, but its long-term oncological effectiveness compared with PN remains uncertain. A quality assessment of pre-existing SRs (n=11) on the topic, using AMSTAR, revealed that all SRs had low confidence rating, with all but two SRs being rated critically low. In conclusion, the current data are inadequate to make any strong and clear conclusions regarding the clinical effectiveness of TA for treating T1N0M0 renal masses compared with PN. Therefore, TA may be cautiously considered an alternative to PN for T1N0M0 renal masses, but patients must be counselled carefully regarding the prevailing uncertainties. We recommend specific steps to improve the evidence base based on robust primary and secondary studies. PATIENT SUMMARY: In this report, we looked at the literature to determine the effectiveness of thermoablation (TA) in the treatment of small kidney tumours compared with surgical removal. We found that TA could cautiously be offered as an option due to many remaining uncertainties regarding its effectiveness., (Copyright © 2020. Published by Elsevier B.V.)

The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic., (Copyright © 2020. Published by Elsevier B.V.)

Pre-operative anaemia is associated with poor outcomes after elective surgery but its relationship with outcomes after emergency surgery is unclear. We analysed National Emergency Laparotomy Audit data from 1 December 2013 to 30 November 2017, excluding laparotomy for haemorrhage. Anaemia was classified as 'mild' 129-110 g.l-1; 'moderate' 109-80 g.l-1; or 'severe' ≤ 79 g.l-1. The primary outcome was 90-day mortality. Secondary outcomes were 30-day mortality, return to theatre and postoperative hospital stay. The primary outcome was available for 86,763 patients, of whom 45,306 (52%) were anaemic. There were 12,667 (15%) deaths at 90 postoperative days and 9246 (11%) deaths at 30 postoperative days. Anaemia was associated with increased 90-day and 30-day mortality, odds ratio (95%CI): mild, 1.15 (1.09-1.21); moderate, 1.44 (1.36-1.52); and severe, 1.42 (1.24-1.63), p < 0.001 for all; mild, 1.07 (1.00-1.12), p = 0.030; moderate, 1.30 (1.21-1.38), p < 0.001; and severe, 1.22 (1.05-1.43), p = 0.010, respectively. All categories of anaemia were associated with prolonged hospital stay, adjusted coefficient (95%CI): mild, 1.31 (1.01-1.62); moderate, 3.41 (3.04-3.77); severe, 2.80 (1.83-3.77), p < 0.001 for all. Moderate and severe anaemia were associated with increased risk of return to the operating theatre, odds ratio (95%CI): moderate 1.13 (1.06-1.21), p < 0.001; and severe 1.23 (1.06-1.43), p = 0.006. Pre-operative anaemia is common in patients undergoing emergency laparotomy and is associated with increased postoperative mortality and morbidity., (© 2020 Association of Anaesthetists.)