In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury.

The hallmark of severe COVID-19 involves systemic cytokine storm and multi-organ injury including testicular inflammation, reduced testosterone, and germ cell depletion. The ACE2 receptor is also expressed in the resident testicular cells, however, SARS-CoV-2 infection and mechanisms of testicular injury are not fully understood. The testicular injury could be initiated by direct virus infection or exposure to systemic inflammatory mediators or viral antigens. We characterized SARS-CoV-2 infection in different human testicular 2D and 3D culture systems including primary Sertoli cells, Leydig cells, mixed seminiferous tubule cells (STC), and 3D human testicular organoids (HTO). Data shows that SARS-CoV-2 does not productively infect any testicular cell type. However, exposure of STC and HTO to inflammatory supernatant from infected airway epithelial cells and COVID-19 plasma decreased cell viability and resulted in the death of undifferentiated spermatogonia. Further, exposure to only SARS-CoV-2 Envelope protein caused inflammatory response and cytopathic effects dependent on TLR2, while Spike 1 or Nucleocapsid proteins did not. A similar trend was observed in the K18-hACE2 transgenic mice which demonstrated a disrupted tissue architecture with no evidence of virus replication in the testis that correlated with peak lung inflammation. Virus antigens including Spike 1 and Envelope proteins were also detected in the serum during the acute stage of the disease. Collectively, these data strongly suggest that testicular injury associated with SARS-CoV-2 infection is likely an indirect effect of exposure to systemic inflammation and/or SARS-CoV-2 antigens. Data also provide novel insights into the mechanism of testicular injury and could explain the clinical manifestation of testicular symptoms associated with severe COVID-19.

Examining potential mechanisms of testicular fibrosis in Klinefelter Syndrome: A review of current understanding.

BACKGROUND: Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding testicular fibrosis in Klinefelter Syndrome patients remains incompletely understood. OBJECTIVES: To perform a systematic review of literature studying the mechanisms of fibrosis initiation or propagation in Klinefelter Syndrome testes. MATERIALS/METHODS: PubMed was searched systematically for articles specific to Klinefelter Syndrome and the process of fibrosis. Articles that did not contain original data or specifically addressed the target material were excluded. Additional references were extracted when pertinent from the reference lists of included studies. RESULTS: Primary search yielded 139 articles for abstract review, which was narrowed to 16 for full-text review. Following full-text review, eight contained original data and met topic criteria, with one paper added from reference review for a total of nine papers. DISCUSSION: The date range for included papers was 1992-2022. The proposed mechanisms of fibrosis mainly were centered around the impact of altered Sertoli cells on germ cells, the hormonal impact on Leydig cells, the inflammation mediated by mast cells, or the fibrous extracellular matrix deposition by peritubular myoid cells. Additionally, discussions of the role of the altered microvasculature and the specific proteins involved in the blood-testis barrier or the seminiferous tubule architecture are reviewed. Recent papers have incorporated advanced sequencing and offer future directions for targeted gene expression analysis. Still, much of the published data consists solely of immunohistological assessment by age range, creating difficulties in extrapolating causality. CONCLUSION: The specific initiating factors of fibrosis of the seminiferous tubules and the propagation mechanisms unique to Klinefelter Syndrome remain incompletely understood with a relative paucity of data. Nonetheless, academic interest is increasing in this field as it may further elucidate the pathophysiology behind Klinefelter syndrome.

In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury.

The hallmark of severe COVID-19 involves systemic cytokine storm and multi-organ failure including testicular injury and germ cell depletion. The ACE2 receptor is also expressed in the resident testicular cells however, SARS-CoV-2 infection and mechanisms of testicular injury are not fully understood. The testicular injury can likely result either from direct virus infection of resident cells or by exposure to systemic inflammatory mediators or virus antigens. We here characterized SARS-CoV-2 infection in different human testicular 2D and 3D models including primary Sertoli cells, Leydig cells, mixed seminiferous tubule cells (STC), and 3D human testicular organoids (HTO). Data shows that SARS-CoV-2 does not establish a productive infection in any testicular cell types. However, exposure of STC and HTO to inflammatory supernatant from infected airway epithelial cells and COVID-19 plasma depicted a significant decrease in cell viability and death of undifferentiated spermatogonia. Further, exposure to only SARS-CoV-2 envelope protein, but not Spike or nucleocapsid proteins led to cytopathic effects on testicular cells that was dependent on the TLR2 receptor. A similar trend was observed in the K18h-ACE2 mouse model which revealed gross pathology in the absence of virus replication in the testis. Collectively, data strongly indicates that the testicular injury is not due to direct infection of SARS-CoV-2 but more likely an indirect effect of exposure to systemic inflammation or SARS-CoV-2 antigens. Data also provide novel insights into the mechanism of testicular injury and could explain the clinical manifestation of testicular symptoms associated with severe COVID-19.

Disparities in Cancer Specific and Overall Survival Outcomes in African Americans With Renal Cell Carcinoma: Analysis From the International Marker Consortium for Renal Cancer (INMARC).

OBJECTIVE: To investigate association of African-American race and survival in Renal Cell Carcinoma (RCC). PATIENTS AND METHODS: We queried the International Marker Consortium for Renal Cancer database for patients who underwent partial or radical (RN) nephrectomy. The cohort was divided into African American (AA) and non-African American (NAA) patients. Primary outcome was all-cause mortality. Secondary outcome was cancer-specific mortality. Multivariable Analysis and Kaplan-Meier Analysis were used to elucidate predictive factors and survival outcomes. RESULTS: Three thousand eight hundred and ninety-three patients were analyzed (AA, n = 564/NAA, n = 3329). AA had greater Stage I (73.8% vs 63.9%, P <.001) and papillary RCC (29.8% vs 8.5%, P <.001). Multivariable Analysis revealed increasing age (HR = 1.03, P <.001), AA (HR = 1.24, P = .027), higher stage (HR = 1.30-3.19, P <.001), RN (HR = 2.45, P <.001), clear cell (HR = 1.23, P <.001), positive margin (HR = 1.34, P .004), and high-grade (HR = 1.58, P <.001) to be associated with worsened all-cause mortality. Increasing age (HR = 1.02, P <.001), AA (HR = 1.48, P = .025), RN (HR = 2.98, P <.001), high-grade (HR = 3.11, P <.001), and higher stage (HR = 3.03-13.2, P <.001) were predictive for cancer-specific mortality. Kaplan-Meier Analysis revealed worsened 5-year overall survival for AA in stage I (80% vs 88%, P = .001), stage III (26% vs 70%, P = .001), and stage IV (23% vs 44%, P = .009). Five-year cancer-specific survival was worse for AA in stage III (36% vs 81%, P <.001) and stage IV (30% vs 49%, P = .007). CONCLUSION: Despite presenting with more indolent histology and lower stage, African-Americans were at greater risk for diminished survival, faring worse in overall survival for all stages and cancer-specific survival in for stage III/IV RCC. Further investigation into factors associated with these disparities is warranted.

A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

Comparison of renal functional outcomes of active surveillance and partial nephrectomy in the management of oncocytoma.

PURPOSE: To compare functional outcomes of partial nephrectomy (PN) and active surveillance (AS) in oncocytoma. METHODS: Multicenter retrospective analysis of patients with oncocytoma managed with PN or AS (biopsy-confirmed). Primary outcome development of de novo chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73m2). Cox regression Multivariable analysis (MVA) was carried out for predictors of de novo CKD. Linear regression was carried out for factors associated with increasing deltaGFR. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year CKD-free survival. RESULTS: 295 patients were analyzed (224 PN/71 AS, median follow-up 37.4 months). No differences were noted for clinical tumor size (AS 2.6 vs. PN 2.9 cm, p = 0.108), and baseline eGFR (AS 79.6 vs. PN 77, p = 0.9670). Median change in tumor diameter for AS was 0.42 cm. Compared to PN, AS had deltaGFR (-15.3 vs. -6.4 mL/min/1.73m2, p < 0.001) and de novo CKD (28.2% vs. 12.1%, p = 0.002). AS patients who developed CKD had higher RENAL score (p = 0.005) and lower baseline eGFR (73 vs. 91.2 mL/min/1.73m2, p < 0.001) than AS patients who did not. MVA demonstrated increasing age (OR = 1.03, p = 0.025), tumor size (HR = 1.26, p = 0.032) and AS (HR = 4.91, p < 0.001) to be predictive for de novo CKD. Linear regression demonstrated AS was associated with larger decrease in deltaGFR (B = -0.219, p < 0.001). KMA revealed 5-year CKD survival was higher in PN (87%) vs. AS (62%, p < 0.001). CONCLUSION: AS was associated with greater functional decline than PN in oncocytoma. PN may be considered to optimalize renal functional preservation in select circumstances. Further investigation into mechanisms of functional decline in oncocytoma is requisite.

Elevated preoperative C-reactive protein is associated with renal functional decline and non-cancer mortality in surgically treated renal cell carcinoma: analysis from the INternational Marker Consortium for Renal Cancer (INMARC).

OBJECTIVE: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC). PATIENTS AND METHODS: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes. RESULTS: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m2 , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001). CONCLUSIONS: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate.

Impact of positive surgical margins on survival after partial nephrectomy in localized kidney cancer: analysis of the National Cancer Database.

BACKGROUND: The impact of positive surgical margins (PSM) on outcomes in partial nephrectomy (PN) is controversial. We investigated impact of PSM for patients undergoing PN on overall survival (OS) in different stages of renal cell carcinoma (RCC). METHODS: Retrospective analysis of patients from the US National Cancer Database who underwent PN for cT1a-cT2b N0M0 RCC between 2004-13. Patients were stratified by pathological stage (pT1a, pT1b, pT2a, pT2b, and pT3a [upstaged]) and analyzed by margin status. Cox Regression multivariable analysis (MVA) was performed to investigate associations of PSM and covariates on all-cause mortality (ACM). Kaplan-Meier analysis (KMA) of OS was performed for PSM versus negative margin (NSM) by pathological stage. Sub-analysis of Charlson Comorbidity Index 0 (CCI=0) subgroup was conducted to reduce bias from comorbidities. RESULTS: We analyzed 42,113 PN (pT1a: 33,341 [79.2%]; pT1a, pT1b: 6689 [15.9%]; pT2a: 757 [1.8%]; pT2b: 165 [0.4%]; and pT3a: upstaged 1161 [2.8%]). PSM occurred in 6.7% (2823) (pT1a: 6.5%, pT1b: 6.3%, pT2a: 5.9%, pT2b: 6.1%, pT3a: 14.1%, P<0.001). On MVA, PSM was associated with 31% increase in ACM (HR 1.31, P<0.001), which persisted in CCI=0 sub-analysis (HR: 1.25, P<0.001). KMA revealed negative impact of PSM vs. NSM on 5-year OS: pT1 (87.3% vs. 90.9%, P<0.001), pT2 (86.7% vs. 82.5%, P=0.48), and upstaged pT3a (69% vs. 84.2%, P<0.001). CONCLUSIONS: PSM after PN was independently associated with across-the-board decrement in OS, which worsened in pT3a disease and persisted in sub-analysis of patients with CCI=0. PSM should prompt more aggressive surveillance or definitive resection strategies.

Infertility considerations in klinefelter syndrome: From origin to management.

Klinefelter syndrome (KS) is defined as the presence of one or more extra "X" chromosome in a male patient. It affects approximately 1 in 600 newborn males and the most common chromosomal abnormality, leading to male hypogonadism and infertility. There is a lack of data supporting best practices for KS patients' care. In this paper we review controversial issues in KS research ranging from mechanisms of variation in KS phenotype to abnormalities resulting in reduced sperm production to successful sperm retrieval disparities after testicular sperm extraction (TESE). Translation to live birth and offspring health is also examined. Finally, medical therapies used to optimize the hormonal status and chances of fertility in KS patients are reviewed. We will also discuss the experimental spermatogonial stem cell (SSC) treatments, which are considered the future for TESE negative patients.

Nephrostomy tubes placed emergently prior to percutaneous renal stone surgery are practical for obtaining access. / La colocación de nefrostomía percutánea antes de la cirugía percutánea de la litiasis facilita la obtención del acceso.

OBJECTIVES: Renal access in percutaneous nephrolithotomy (PCNL) may be obtained via a pre-existing nephrostomy tube (NT) tract; however, emergent NTs are not always ideal for subsequent surgery. We sought to determine the rate of NT tract usability and assess factors related to the usability of emergently placed NTs. METHODS: A retrospective review was performed of UC San Diego subjects undergoing percutaneous renal surgery between January 2016 and October 2018. Demographics and peri-operative variables were collected. The primary outcome was the usability of NT tract for dilation and instrumentation. "Usable" indicated a tract in which PCNL could be completed; "unusable" indicated lack of dilation and the requirement of additional tract(s) for PCNL. RESULTS: 35 PCNL cases had previous emergently placed NT which were indwelling at time of percutaneous surgery. 51% of these NT tracts (18/35) were deemed usable and dilated for PCNL. No significant difference was seen between usable and unusable NT groups for number of dilated tracts during PCNL (p=0.13), or either the location of indwelling NT (p=0.96) or renal stones (p=0.95). In the usable NT tract cohort PCNL access was via the lower pole 56% of the time, where as when previous NT tracts were deemed unusable, a separate upper-pole access was obtained intra-operatively 53% of the time (p<0.01). CONCLUSIONS: Pre-existing, emergent NTs served a ssufficient PCNL access tracts in over half of recorded cases. Contrary to recently published reports, the utility of pre-existing NTs appears to vary among health systems. Other variables, including the desired location of PCNL appear to directly influence the like lihood of NT tract usability.

OBJETIVOS: El acceso renal en la nefrolitotomía percutánea puede obtenerse a través de una nefrostomía pre-existente, aunque las nefrostomías urgentes no siempre son ideales para la posterior cirugía. Nosotros intentamos determinar la tasa de uso del tracto de nefrostomía y los factores de acceso relacionados con el uso de la nefrostomía urgente.MÉTODOS: Una revisión retrospectiva se realizó en UC San Diego de los pacientes que habían recibido cirugía renal percutánea entre enero 2016 y octubre 2018. Las variables demográficas y perioperatorias fueron recolectadas. El objetivo primario fue el uso del trayecto de nefrostomía después de dilatación e instrumentación.¨Usable"  indicó un trayecto en el que la nefrolitotomía percutánea se completo. "No usable" indicó falta de dilatación y el requerimiento de un nuevo trayecto para la cirugía percutánea. RESULTADOS: 35 casos de nefrolitotomía percutánea tenían nefrostomías urgentes previamente y presentes al empezar la cirugía. 51% de estos trayectos (18/35) fueron usados y dilatados para la nefrolitotomía percutánea. No hubo diferencias significativas entre los trayectos usables y no usables en el numero de trayectos dilatados durante la cirugía percutánea (p=0,13), ni en la localización de la sonda de nefrostomía (p=0,96) o las litiasis renales (p=0,95). En el grupo de pacientes con nefrostomía usable, en el 56% la nefrostomía accedía por el polo inferior. Cuando el trayecto de nefrostomía se considero no usable, un nuevo acceso intraoperatorio por el polo superior fue obtenido en el 53% de lo scasos (p<0,01). CONCLUSIONES: El trayecto de nefrostomía pre-existente fue suficiente para el acceso percutáneo en la mitad de los casos. Contrario a lo publicado recientemente, la utilidad de la nefrostomía pre-existente parece variar según el Sistema sanitario. Otras variables, incluyendo la localización deseada para la nefrostomía influencia el uso del trayecto.

Oncologic and Functional Outcomes of Radical and Partial Nephrectomy in pT3a Pathologically Upstaged Renal Cell Carcinoma: A Multi-institutional Analysis.

BACKGROUND: The efficacy of partial nephrectomy (PN) in setting of pT3a pathologic-upstaged renal cell carcinoma (RCC) is controversial. We compared oncologic and functional outcomes of radical nephrectomy (RN) and PN in patients with upstaged pT3a RCC. PATIENTS AND METHODS: This was a multicenter retrospective analysis of patients with cT1-2N0M0 RCC upstaged to pT3a postoperatively. The primary outcome was recurrence-free survival, with secondary outcomes of overall survival and de novo estimated glomular filtration rate (eGFR) < 60. Multivariable analysis was performed to identify predictive factors for oncologic outcomes. Kaplan-Meier analyses (KMA) were obtained to elucidate survival outcomes. RESULTS: A total of 929 patients had pT3a upstaging (686 [72.6%] RN; 243 [25.7%] PN; mean follow-up, 48 months). Tumor size was similar (RN 7.7 cm vs. PN 7.3 cm; P = .083). PN had decreased ΔeGFR (6.1 vs. RN 19.4 mL/min/1.73m2; P < .001) and de novo eGFR < 60 (9.5% vs. 21%; P = .008). Multivariable analysis for recurrence showed increasing RENAL score (hazard ratio [HR], 3.8; P < .001), clinical T stage (HR, 1.8; P < .001), positive margin (HR, 1.57; P = .009), and high grade (HR, 1.21; P = .01) to be independent predictors, whereas surgery was not (P = .076). KMA revealed 5-year recurrence-free survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 79%, 74%, 70%, and 51%, respectively (P < .001). KMA revealed 5-year overall survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 64%, 65.2%, 56.4%, and 55.2%, respectively (P = .059). CONCLUSIONS: In pathologically upstaged pT3a RCC, PN did not adversely affect risk of recurrence and provided functional benefit. Surgical decision-making in patients at risk for T3a upstaging should be individualized and driven by tumor as well as functional risks.

Robotic partial nephrectomy vs minimally invasive radical nephrectomy for clinical T2a renal mass: a propensity score-matched comparison from the ROSULA (Robotic Surgery for Large Renal Mass) Collaborative Group.

OBJECTIVE: To compare outcomes of minimally invasive radical nephrectomy (MIS-RN) and robot-assisted partial nephrectomy (RAPN) in clinical T2a renal mass (cT2aRM). PATIENTS AND METHODS: Retrospective, multicentre, propensity score-matched (PSM) comparison of RAPN and MIS-RN for cT2aRM (T2aN0M0). Cohorts were PSM for age, sex, body mass index, American Society of Anesthesiologists (ASA) class, clinical tumour size, and R.E.N.A.L. score using a 2:1 ratio for RN:PN. The primary outcome was disease-free survival (DFS). Secondary outcomes included overall survival (OS), complication rates, and de novo estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 . Multivariable (MVA) and Kaplan-Meier survival analyses (KMSA) were conducted. RESULTS: In all, 648 patients (216 RAPN/432 MIS-RN) were matched. There were no significant differences in intraoperative complications (P = 0.478), Clavien-Dindo Grade ≥III complications (P = 0.063), and re-admissions (P = 0.238). The MVA revealed high ASA class (hazard ratio [HR] 2.7, P = 0.044) and sarcomatoid (HR 5.3, P = 0.001), but not surgery type (P = 0.601) to be associated with all-cause mortality. Increasing R.E.N.A.L. score (HR 1.31, P = 0.037), high tumour grade (HR 2.5, P = 0.043), and sarcomatoid (HR 2.8, P = 0.02) were associated with recurrence, but not surgery (P = 0.555). Increasing age (HR 1.1, P < 0.001) and RN (HR 3.9, P < 0.001) were predictors of de novo eGFR of <45 mL/min/1.73 m2 . Comparing RAPN and MIS-RN, KMSA revealed no significant differences for 5-year OS (76.3% vs 88.0%, P = 0.221) and 5-year DFS (78.6% vs 85.3%, P = 0.630) for pT2 RCC, and no differences for 3-year OS (P = 0.351) and 3-year DFS (P = 0.117) for pT3a upstaged RCC. The 5-year freedom from de novo eGFR of <45 mL/min/1.73 m2 was 91.6% for RAPN vs 68.9% for MIS-RN (P < 0.001). CONCLUSIONS: RAPN had similar oncological outcomes and morbidity profile as MIS-RN, while conferring functional benefit. RAPN may be considered as a first-line option for cT2aRM.

Antibiotics are not necessary during routine cystoscopic stent removal: A randomized controlled trial at UC San Diego.

INTRODUCTION: Current American Urological Association (AUA) Best Practice Statement recommends antibiotic prophylaxis for cystoscopy with manipulation, including stent removal; although no Level 1b trials explicitly address prophylaxis for stent removal. We sought to determine the efficacy of prophylactic antibiotics to prevent infectious complications after stent removal. MATERIALS AND METHODS: Following institutional review board approval, patients undergoing removal of ureteral stent placed during stone surgery were recruited from July 2016 to March 2019. Patients were recruited at the time of stent removal and randomized to treatment (single dose 500 mg oral ciprofloxacin) or control group (no antibiotics). Telephone contact was attempted within 14 days of stent removal to assess for urinary tract infection (UTI) symptoms, antibiotic prescriptions, or Emergency Department visits. Primary outcome was UTI within 1 month of stent removal - defined by irritative voiding symptoms, fever or abdominal pain associated with positive urine culture (Ucx) (>100k colony-forming units/mL). RESULTS: Seventy-seven patients were enrolled, with 58 meeting final inclusion criteria for the analysis (33 treatment, 25 controls). No differences were seen with clinical and demographic variables, except a higher body mass index in the treatment group (P = 0.007). Positive Ucx rate before stone surgery (16.7% vs. 11.8%, P = 0.819) and at the time of stent removal (16.0% vs. 11.1%, P = 0.648) was not significantly different in treatment versus control groups, respectively. Primary outcome: No patients in either cohort developed symptomatic culture-diagnosed UTI within 1 month of stent removal. Of patients with documented phone follow-up (treatment n = 29, control n = 22), only one patient (control) reported any positive response on phone survey. CONCLUSIONS: We found a low infectious complication rate regardless of antibiotic prophylaxis use during cystoscopic stent removal. The necessity of antibiotics during routine cystoscopic stent removal warrants possible reevaluation of the AUA best practice statement.

Robotic partial nephrectomy for clinical T2a renal mass is associated with improved trifecta outcome compared to open partial nephrectomy: a single surgeon comparative analysis.

OBJECTIVE: Utilization of partial nephrectomy (PN) for T2 renal mass is controversial due to concerns regarding burden of morbidity, though most cited data are from open PN (OPN). We compared surgical quality and functional outcomes of RPN and OPN for clinical T2a renal masses (cT2aRM). METHODS: Retrospective analysis of 150 consecutive patients [RPN 59/OPN 91] who underwent PN from July 2008 to June 2016. Main outcome was achievement of Trifecta [negative surgical margin, no major urologic complications, and ≥90% preservation of estimated glomerular filtration rate (eGFR)]. Multivariable analysis was performed to identify factors of Trifecta attainment. RESULTS: Mean tumor size (RPN 7.9 vs. OPN 8.4 cm, p = 0.139) and median RENAL score (p = 0.361) were similar. No difference was noted for positive margins (RPN 3.4% vs. OPN 1.1%, p = 0.561), ΔeGFR (RPN - 6.2 vs. OPN - 7.8, p = 0.543), and ≥ 90% eGFR recovery (RPN 54.1% vs. OPN 47.2%, p = 0.504). RPN had lower blood loss (p = 0.015), hospital stay (p = 0.013), and Clavien ≥ 3 complications (RPN 5.1% vs. OPN 16.5%, p = 0.041). Trifecta rate was significantly higher in RPN (47.5% vs. 34.0%, p = 0.041). Multivariable analysis demonstrated decreasing RENAL score (OR 1.11, p < 0.001), RPN (OR 1.2, p = 0.013), and decreasing EBL (OR 1.02, p = 0.016) to be associated with Trifecta attainment. CONCLUSIONS: RPN provided similar functional and oncologic precision to OPN, while being associated with improvements in major complications, the latter of which was reflected in a higher rate of Trifecta achievement for RPN. RPN may be considered to be a first-line option for select patients with cT2aRM when feasible and safe.

Risk Factors for Upstaging, Recurrence, and Mortality in Clinical T1-2 Renal Cell Carcinoma Patients Upstaged to pT3a Disease: An International Analysis Utilizing the 8th Edition of the Tumor-Node-Metastasis Staging Criteria.

OBJECTIVE: To investigate risk factors for and outcomes in pathological T3a-upstaging in Renal Cell Carcinoma (RCC), as Tumor-Node-Metastasis staging for T3a RCC was recently revised. METHODS: Multicenter retrospective analysis of patients with clinical T1-T2 RCC, stratified by occurrence of pathologic T3a-upstaging. Primary outcome was recurrence-free survival (RFS). Multivariable analyses (MVA) were conducted for upstaging and recurrence. Kaplan-Meier analysis (KMA) was utilized for RFS and overall survival (OS). RESULTS: We analyzed 2573 patients (1223 RN/1350 PN). Upstaging occurred in 360 (14.0%). On MVA, higher clinical stage was associated with increasing risk of upstaging [cT1a (referent), odds ratio for cT1b, cT2a, and cT2b was 2.6, 6.5, and 14.1, P < .001]. Higher clinical stage at presentation correlated with increasing risk of recurrence in pT3a-upstaged RCC (cT1a upstaged-pT3a [referent], hazard ratio [HR] for cT1b, cT2a, and cT2b upstaged pT3a was 1.16 [P = .729], 3.02 [P = .013], and 4.5 [P = .003]). Perirenal fat (HR 1.6, P = .038) and renal vein (HR 2.2, P = .006) invasion were associated with increased risk of recurrence; type of surgery was not (P = .157). KMA for RFS and OS in pT3a-upstaged patients demonstrated differences based on initial clinical stage (5-year PFS for cT1a/b, and cT2 upstaged was 84.5%/72.8%, and 44.7%, P < .001; 5-year OS for cT1 and cT2 upstaged was 83.8% and 63.2%, P < .001). CONCLUSION: Risk of pT3a-upstaging and recurrence in pT3a-upstaged RCC correlates with clinical stage at presentation. Renal vein and perinephric fat invasion were associated with increased risk of recurrence. PN did not increase risk of recurrence and potential of pT3a-upstaging should not deter consideration of PN.

Systemic therapy in the management of localized and locally advanced renal cell carcinoma: Current state and future perspectives.

Systemic therapy strategies in the setting of localized and locally advanced renal cell carcinoma have continued to evolve in two directions: (i) as adjuvant therapy (to reduce the risk of recurrence or progression in high-risk localized groups); or (ii) as neoadjuvant therapy as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron-sparing surgery was not thought to be safe or feasible. In the realm of adjuvant therapy, the results of adjuvant therapy phase III randomized clinical trials have been mixed and contradictory; nevertheless, the findings of the landmark Sunitinib Treatment of Renal Adjuvant Cancer study have led to approval of sunitinib as an adjuvant agent in the USA. In the realm of neoadjuvant therapy, presurgical tumor reduction has been shown in a number of phase II studies utilizing targeted molecular agents and in a recently published small randomized double-blind placebo-controlled study, and an expanding body of literature suggests benefit in select patients. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for adjuvant and neoadjuvant strategies. The present article reviews the current status and future prospects of adjuvant and neoadjuvant therapy in localized and locally advanced renal cell carcinoma.