Lipid droplet formation is a defining histological feature in clear-cell renal cell carcinoma (ccRCC) but the underlying mechanisms and importance of this biological behaviour have remained ...enigmatic. De novo fatty acid (FA) synthesis, uptake and suppression of FA oxidation have all been shown to contribute to lipid storage, which is a necessary tumour adaptation rather than a bystander effect. Clinical studies and mechanistic investigations into the roles of different enzymes in FA metabolism pathways have revealed new metabolic vulnerabilities that hold promise for clinical effect. Several metabolic alterations are associated with worse clinical outcomes in patients with ccRCC, as lipogenic genes drive tumorigenesis. Enzymes involved in the intrinsic FA metabolism pathway include FA synthase, acetyl-CoA carboxylase, ATP citrate lyase, stearoyl-CoA desaturase 1, cluster of differentiation 36, carnitine palmitoyltransferase 1A and the perilipin family, and each might be potential therapeutic targets in ccRCC owing to the link between lipid deposition and ccRCC risk. Adipokines and lipid species are potential biomarkers for diagnosis and treatment monitoring in patients with ccRCC. FA metabolism could potentially be targeted for therapeutic intervention in ccRCC as small-molecule inhibitors targeting the pathway have shown promising results in preclinical models.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Studies have repeatedly demonstrated salary-based gender disparities in the field of Urology. These disparities persist even when accounting for contributing factors such as years of experience, ...hours worked, and practice setting, suggesting that inherent gender bias exists. In addition to salary discrepancies, female urologists are also less likely to be promoted and less likely to hold leadership positions as compared to male urologists. We review the data supporting these disparities and provide tangible, evidence-based solutions for the field of Urology going forward.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Black men face a higher incidence of high-risk prostate cancer (PCa) compared with non-Black men. While the 4Kscore is a widely utilized commercial test for PCa risk assessment, it does not currently ...account for racial differences. The aim of this study is to describe and validate a prespecified race coefficient for the 4Kscore with the goal of improving the accuracy of this test for Black men.
Using data from 85 Black men from the initial US prospective validation study, a race coefficient of 0.6 on the log-odds scale was prespecified. We calculated discrimination, calibration, and clinical utility of the 4Kscore with and without this coefficient for Black race in our primary analysis cohort of 205 Black men undergoing biopsy for PCa in a Veterans Affairs (VA) institution. We performed a sensitivity analysis using a combined cohort from the US prospective validation and the VA studies.
The mean probability of high-grade PCa from the 4Kscore in the primary cohort increased from 25% to 37% with race coefficient addition. Incorporating the race coefficient improved 4Kscore's calibration in Black men, with consequent improvements in clinical utility based on decision curve analysis. Model discrimination was maintained (AUC 0.825 vs 0.828,
= .14) in the combined cohort of Black and non-Black men from the US prospective and VA studies and the calibration remained largely unchanged.
Incorporating a prespecified coefficient for Black race improved calibration and clinical utility of the 4Kscore among Black men and should be added to the 4Kscore.
Gender-affirming vaginectomy treats gender dysphoria associated with the presence of a vagina in transgender males.1,2 Prior reported approaches include transperineal vaginectomy, mucosal ...fulguration, and robotic-assisted. We present key steps in transperineal gender-affirming vaginectomy in a 39-year-old transgender male.
Informed consent for video recording was obtained. The patient underwent a first-stage phalloplasty 6 months prior. He was placed in high lithotomy Tredelenberg position. After Foley placement, an incision was made along the mucocutaneous junction laterally and posteriorly. The anterior sulci were incised and a transverse incision made anteriorly at the bladder neck. The vaginal mucosa was excised, except for the distal anterior vaginal wall mucosa which would be mobilized as a flap for urethral lengthening later. The paravaginal space was closed with a series of purse-string sutures starting at the apex. The anterior vaginal wall flap is mobilized with the base of the flap at the urethral meatus. Cystoscopy confirms ureteral patency and no lower urinary tract involvement. A suprapubic tube was placed. The procedure then proceeded with a second-stage phalloplasty that included urethral lengthening and scrotoplasty.
The demonstrated procedure took 110 minutes and estimated blood loss was 75 mL. In our published series of 40 vaginectomies for 27 phalloplasties and 13 metoidioplasties, median operative time was 135 minutes and median estimated blood loss was 250cc.3 No complications related to the vaginectomy, including mucocele, fistulae to the vaginal space, or visceral injuries occurred. Peritoneal entry occurred in 44% of the cases and was closed primarily without further sequelae. Two patients required blood transfusion and 1 patient had C. difficile colitis. The anterior vaginal wall mucosa flap was incorporated in 83% of the time.
Transperineal vaginectomy results in low periprocedural complications, takes approximately 2 hours after a learning curve. Detailed results from our series of these procedures have been previously reported.3
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To investigate if localized amyloidosis of the seminal tract (LAST) is associated with subsequent development of systemic amyloidosis. Prior reports recorded no systemic amyloidosis at the time of ...LAST diagnosis. However, no follow-up studies exist to confirm that LAST is not a risk factor for subsequent development of systemic amyloidosis.
Our study cohort included patients whose prostate biopsy (PB) or radical prostatectomy (RP) specimen demonstrated LAST between 2014–2021. Clinical variables including age, race/ethnicity, prostate specific antigen (PSA), and prostate weight were analyzed. Patients were assessed for clinical and laboratory evidence of systemic amyloidosis and lymphoproliferative conditions during the follow-up period.
Thirty-six men (26 RPs, 9 PBs, and 1 cystoprostatectomy) had LAST. Our study cohort included 18 white Hispanic, 9 white non-Hispanic, 7 black, and 1 Asian men. Median age was 67 years, mean PSA was 9.8 ng/mL. Over a median follow-up period of 20 months (mean, 30) in 27 men, none developed systemic amyloidosis. Frequency of LAST in RP specimens was 1.2% (26/2,135) and corelated with age (67 vs 63 years, P-value = .004). Race/ethnicity, PSA, and prostate weight were not associated with the incidence of LAST.
LAST is not a harbinger of systemic disease. The incidence of LAST in a contemporary RP cohort is significantly lower than in previously published studies. While patient age positively corelates with LAST, PSA and prostate weight are not associated with the condition. There is no difference in the frequency of LAST between white Hispanic, white non-Hispanic, and black men.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To study patterns and factors associated with female representation in the American Urological Association (AUA) guidelines.
We gathered publicly available information about the panelists, including ...the AUA section, practice setting, academic rank, fellowship training, years in practice, and H-index. The factors associated with the proportion of female panelists and trends were investigated. We also examined the proportion of female panelists in the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) urology guidelines.
There were 483 non-unique panelists in AUA guidelines, and 17% are female. Non-urologist female panelists in AUA guidelines represented a higher proportion than female urologists (30% vs 13%, P<0.0001). Compared with male panelists, females had lower H-indices (median 23 vs 35, P<0.001), and fewer were fellowship-trained (77.2% vs 86.8%; P=0.042). On multivariate analysis, non-urologists and panelists with lower H-indices were more likely to be female but there was no association between guideline specialties, academic ranking, geographic section, years in practice, and fellowship training with increased female authorship. Overtime, the proportion of female participation in guidelines remained stable. In the EAU and NCCN guideline panels, 12.2% and 10.7% were female, respectively.
Female representation among major urologic guidelines members is low and unchanged overtime. Female urologist participation was proportional to their representation in the urology workforce. Being a non-urologist and lower H-indices were associated with female membership in guideline panels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
For patients with clinical suspicion of prostate cancer, liquid biomarkers are the next best test because of their accessibility, objectiveness, and noninvasive nature. A highly sensitive cutoff for ...these biomarkers should be used to triage patients before use of magnetic resonance imaging.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Of the 1,312 patients, 939 (71%) developed metastases, and 113 (8.6%) had metastases to 5 or more distinct anatomical sites (defining wide-spread metastases, WSM).•Among patients with metastasis, ...increasing number of metastatic sites was associated with increased risk of death (HR: 1.8, 95%CI: 1.63–1.99, P < 0.001).•In a univariable survival analysis, the following alterations were predictive of overall survival (OS) (P < 0.05): TP53 (40% vs. 20%, P < 0.0001), FOXA1-amplification (8% vs. 3%, P = 0.02), AR-amplification (4.4% vs. 1%, P = 0.01), RB1-deletion (5.3% vs. 0.7%, P = 0.001), and BRCA2-deletion (4.4% vs. 0.7%, P = 0.01).•On multivariable analysis, only TP53 mutations, FOXA1, and AR amplifications were independent prognostic factors.•Patients who have either AR or FOXA1 amplifications experienced very poor OS (HR:3.57, 95%CI:2.26–5.6, P < 0.001).
Emerging evidence suggests that metastasis is better described as a spectrum of disease rather than a binary state. A greater understanding of the genomic features that determine extent and location of metastatic spread may inform risk stratification and monitoring. Here, we identify genomic alterations from primary prostate carcinomas that are predictive of wide-spread metastatic potential.
Genomic and clinical data from 1,312 patients with primary prostate carcinoma were extracted from the MSK-MET cohort through cBioPortal. Metastatic site counts and overall survival (OS) data were publicly available and used as the primary outcomes. Primary tumor samples were profiled using the MSK-IMPACT targeted sequencing platform. We focused on 58 genes frequently altered in prostate cancer. Cox proportional hazard analyses defined hazard ratios (HRs) and 95% confidence intervals (CIs) for overall mortality in patients with different metastatic outcomes.
Out of the 1,312 patients in our cohort, 939 (71%) developed metastases, of whom 113 (8.6%) had metastases to 5 or more distinct anatomical sites (defining wide-spread metastases, WSM). Bone was the most common site of metastasis (36%), and 80% of patients with liver metastases had 4 or more additional sites of metastasis. Among patients with metastasis, increasing number of metastatic sites was associated with increased risk of death (HR: 1.8, 95%CI: 1.63–1.99, P < 0.001). Alterations in the following genes were enriched in tumors from patients with WSM vs. others: TP53 (40% vs. 20%, P < 0.0001), FOXA1-amplification (8% vs. 3%, P = 0.02), AR-amplification (4.4% vs. 1%, P = 0.01), RB1-deletion (5.3% vs. 0.7%, P = 0.001), and BRCA2-deletion (4.4% vs. 0.7%, P = 0.01). Univariable survival analysis showed all these alterations were predictive of OS (P < 0.05). On multivariable analysis, only TP53 mutations, and FOXA1 and AR amplifications were independent prognostic factors. FOXA1 (n = 37) and AR (n = 13) amplifications were mutually exclusive and patients with these experienced very poor OS (HR: 3.57, 95%CI:2.26–5.6, P < 0.001.
We identified genomic alterations (TP53 mutations, FOXA1/AR amplification, RB1/BRCA2 deletion) from primary prostate carcinomas that are predictive of wide-spread metastases and poor outcome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
