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Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease., Competing Interests: All conflicts of interest, including specific financial interests and relationships and affiliations relevant or not relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are as follows: Singer EA: Astellas/Medivation: Research support to institution; Johnson & Johnson: Advisory board; Merck: Advisory board; Vyriad: Advisory board; Aura Biosciences: Data safety–monitoring board; Saraiya B: Merck, Regeneron: Research support to institution., (Copyright: Lichtbroun BJ, et al.)

Cardiac metastases from renal cell carcinoma (RCC) are very rare. We describe the case of a woman with RCC with cardiac metastases involving the entire right atrium, penetrating through the myocardium, with extension into the tricuspid valve and right ventricle. This report highlights the unique challenge of the diagnosis and treatment of cardiac metastases in RCC., Competing Interests: The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this article., (Copyright: Cahill EM, et al.)

Purpose: During COVID-19, many operating rooms were reserved exclusively for emergent cases. As a result, many elective surgeries for renal cell carcinoma (RCC) were deferred, with an unknown impact on outcomes. Since surveillance is commonplace for small renal masses, we focused on larger, organ-confined RCCs. Our primary endpoint was pT3a upstaging and our secondary endpoint was overall survival., Materials and Methods: We retrospectively abstracted cT1b-T2bN0M0 RCC patients from the National Cancer Database, stratifying them by clinical stage and time from diagnosis to surgery. We selected only those patients who underwent surgery. Patients were grouped by having surgery within 1 month, 1-3 months, or >3 months after diagnosis. Logistic regression models measured pT3a upstaging risk. Kaplan Meier curves and Cox proportional hazards models assessed overall survival., Results: A total of 29,746 patients underwent partial or radical nephrectomy. Delaying surgery >3 months after diagnosis did not confer pT3a upstaging risk among cT1b (OR = 0.90; 95% CI: 0.77-1.05, P = 0.170), cT2a (OR = 0.90; 95% CI: 0.69-1.19, P = 0.454), or cT2b (OR = 0.96; 95% CI: 0.62-1.51, P = 0.873). In all clinical stage strata, nonclear cell RCCs were significantly less likely to be upstaged (P <0.001). A sensitivity analysis, performed for delays of <1, 1-3, 3-6, and >6 months, also showed no increase in upstaging risk., Conclusion: Delaying surgery up to, and even beyond, 3 months does not significantly increase risk of tumor progression in clinically localized RCC. However, if deciding to delay surgery due to COVID-19, tumor histology, growth kinetics, patient comorbidities, and hospital capacity/resources, should be considered., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The human microbiome contains a vast network of understudied organisms that have an intimate role in our health and wellness. These microbiomes differ greatly between individuals, creating what may be thought of as a unique and dynamic microbial signature. Microbes have been shown to have various roles in metabolism, local and systemic inflammation, as well as immunity. Recent findings have confirmed the importance of both the gut and urinary microbiomes in genitourinary malignancies. Numerous studies have identified differences in microbial signatures between healthy patients and those with urologic malignancies. The microbiomes have been shown to contain microbes that may contribute to the etiology of disease state as well as yield information in regard to a person's health and their responsiveness to certain drugs such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Less well understood are the effects of antibiotics on oncologic outcomes in such treatment courses. This review will explore our current understanding and advancements in the field of microbiome research and discuss its intimate association with genitourinary diseases including bladder cancer, prostate cancer, and kidney cancer. With a better understanding of the association between the microbiome and genitourinary malignancy, further investigation may produce reliable predictors of disease, prognostic indicators as well as therapeutic targets., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-2976). EAS receives research support from Astellas/Medivation. EAS is an of the Editorial Board Member. The authors have no other conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Purpose of Review: As the biology of metastatic renal cell carcinoma (mRCC) continues to be elucidated, novel treatments focused around immunotherapies and targeted therapies will continue to emerge. In this review, we will highlight recent treatment advances and their implications for surgical and systemic therapy., Recent Findings: Several new treatments, including the tyrosine kinase inhibitor cabozantinib, the combination of a programmed cell death protein 1 antibody (nivolumab) with a cytotoxic T-lymphocyte-associated antigen 4 antibody (ipilimumab), and the combination of axitinib with pembrolizumab or avelumab have been approved by the US Food and Drug Administration as first-line therapy for the treatment of mRCC. Although promising survival benefits have been seen with these new therapies, careful patient selection is still critical., Summary: The introduction of novel therapies and the investigation of combinatorial therapies have shifted the treatment paradigm for advanced RCC. Present trials have provided promising data that could lead to further therapeutic advances.

The objective of this study is to report a benign mesenchymal neoplasm, cellular angiofibroma. We describe a 34-year-old male with a 4-month history of a painless right inguinal mass. CT scan of the abdomen and pelvis showed a 6.6 cm, oval-shaped mass without any distinguishing radiographical features. Surgical excision of the mass was performed. Tissue was extracted for immunohistochemical analysis, which stained positive for CD34 and Desmin, confirming cellular angiofibroma of the spermatic cord. Thus, this report highlights the importance of a challenging diagnostic case for providers due to the narrow range of imaging modalities and therefore limited treatment options., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Lymph node (LN) involvement in renal cell carcinoma (RCC) is associated with a poor prognosis. While lymph node dissection (LND) may provide diagnostic information, its therapeutic benefit remains controversial. Thus, the aim of our study is to analyze survival outcomes after LND for nonmetastatic RCC and to characterize contemporary practice patterns., Materials and Methods: The National Cancer Database was queried for patients with nonmetastatic RCC who underwent either partial or radical nephrectomy from 2010 to 2014. A total of 11,867 underwent surgery and LND. Chi-square tests were used to examine differences in patient demographics. To minimize selection bias, propensity score matching (PSM) was used to select one control for each LND case (n = 19,500). Cox regression analyses were conducted to examine overall survival (OS) in patients who received LND compared to those who did not., Results: Of all patients undergoing LND for RCC (n = 11,867), 5%, 23%, 31%, 47% were performed for tumors of clinical T stage 1, 2, 3, and 4, respectively. Proportions of LND have not significantly changed from 2010 to 2014. No significant improvement in median OS for patients undergoing LND compared to no LND was shown (34.7 vs. 34.9 months, respectively; P = 0.98). Similarly, no significant improvement in median OS was found for clinically LN positive patients undergoing LND compared to no LND (P = 0.90). On Cox regression analysis, LND dissection was not associated with an OS benefit (hazard ratio: 1.00; 95% confidence interval 0.97 to 1.04)., Conclusions: Among all RCC patients, LNDs are often performed for low stage disease, suggesting a potential overutilization of LND. No OS benefit was seen in any subgroup of patients undergoing LND. Further investigation is needed to determine which patient populations may benefit most from LND., (Copyright © 2018. Published by Elsevier Inc.)

Background: Prostate cancer remains the second leading cause of cancer related death in men. Immune check point blocking antibodies have revolutionized treatment of multiple solid tumors, but results in prostate cancer remain marginal. Previous reports have suggested that local therapies, in particular cryoablation might increase tumor immunogenicity. In this work, we examine potential synergism between tumor cryoabalation and check point blocking antibodies., Methods: FVB/NJ mice were injected subcutaneously into each flank with either 1 × 10 6 or 0.2 × 10 6 isogenic hormone sensitive Myc-Cap cells to establish synchronous grafts. Mice were treated with four intraperitoneal injections of anti-PD-1 (10 mg/kg), anti-CTLA-4 (1 mg/kg), or isotype control antibody with or without adjuvant cryoablation of the larger tumor graft and with or without neo-adjuvant androgen deprivation with degarelix (ADT). Mouse survival and growth rates of tumor grafts were measured. The immune dependency of observed oncological effects was evaluated by T cell depletion experiments., Results: Treatment with anti-CTLA-4 antibody and cryoablation delayed the growth of the distant tumor by 14.8 days (p = 0.0006) and decreased the mortality rate by factor of 4 (p = 0.0003) when compared to cryoablation alone. This synergy was found to be dependent on CD3 +  and CD8 +  cells. Combining PD-1 blockade with cryoablation did not show a benefit over use of either treatment alone. Addition of ADT to anti-PD1 therapy and cryoablation doubled the time to accelerated growth in the untreated tumors (p = 0.0021) and extended survival when compared to cryoablation combined with ADT in 25% of the mice. Effects of combining anti-PD1 with ADT and cryoablation on mouse survival were obviated by T cell depletion., Conclusion: Trimodal therapy consisting of androgen deprivation, cryoablation and PD-1 blockade, as well as the combination of cryoablation and low dose anti-CTLA-4 blockade showed that local therapies with cryoablation could be considered to augment the effects of checkpoint blockade in prostate cancer.

Postprostatectomy urinary incontinence has a significant impact on the quality of life of patients who undergo radical prostatectomy. Stress and overflow incontinence may result from the procedure, with sphincteric incompetence and detrusor hypocontractility implicating their development, respectively. In many cases, treatment begins with conservative approaches, including pelvic floor muscle training or biofeedback. Pharmacotherapy can be used to treat overactive bladder. For stress incontinence, transurethral bulking agents are utilized in select patients; however, artificial urinary sphincter and male slings are the most efficacious options with good success rates. In this review, the various treatment modalities are critically discussed with special emphasis on safety and efficacy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Radical cystectomy (RC) with ileal conduit (IC) or continent diversion (CD) is standard treatment for high-risk non-invasive and muscle-invasive bladder cancer., Objective: Our aim is to study contemporary trends in the utilization of ICs and CDs in patients undergoing RC., Methods: Using the National Inpatient Sample 2001-2012, we identified all patients diagnosed with a malignant bladder neoplasm who underwent RC followed by IC or CD. Patient demographics, comorbidities, length of stay (LOS), and in-hospital complications, mortality, and costs were compared. Multivariable logistic regression analysis, Chi square, and t -tests were used for analysis., Results: Between 2001-2012, approximately 69,049 ICs and 6,991 CDs were performed. CDs increased from 2001 to 2008, but declined after 2008 ( p  < 0.0001). Patients of all ages received ICs at a higher rate than CDs (40-59 years: 79.5% vs. 20.5%; 60-69 years: 88.0% vs. 12.0%; p  < 0.0001). There was a difference in males vs. females (10.2% vs. 4.0%; OR 2.36) and Caucasians vs. African Americans (9.0% vs. 6.7%; OR 1.49) when comparing CD rates. CD rates were highest in the West, urban teaching centers, and large hospitals ( p  < 0.001). ICs were associated with higher rates of overall postoperative complications ( p  = 0.0185) including infection ( p  = 0.002) and mortality ( p  < 0.0001). In-hospital costs were greater for the CD group., Conclusions: The number of CDs has declined recently. Patients of all ages are more likely to receive ICs than CDs. Gender, racial, and geographic disparities exist among those receiving CDs. CDs are associated with lower rates of in-hospital complications and mortality, but higher in-hospital costs.

Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.

Introduction: Mechanical bowel preparation (MBP) has historically been the standard of care for patients undergoing reconstructive urologic surgery, including urinary diversion. To date, several studies have examined the role of mechanical bowel preparation in postoperative outcomes in pediatric patients undergoing augmentation cystoplasty. However, these patient populations have been heterogeneous in nature, with no studies dedicated to examining the role of MBP prior to reconstructive urologic surgery in pediatric patients with myelomenginoceles. Thus, our objective was to retrospectively assess perioperative measures and postoperative complications after reconstructive urologic surgery with or without mechanical bowel preparation in pediatric myelomeningocele patients., Materials and Methods: From 2008 to 2013, 80 patients with myelomeningocele underwent reconstructive urologic surgery involving the use of bowel. Seventy patients underwent a preoperative MBP while 10 did not. Perioperative measures and postoperative complications for these two cohorts were assessed., Results: Eighty patients with myelomeningocele were identified; 70 patients underwent MBP while 10 patients did not. There were no statistically significant differences in demographics or operative time. There were no statistically significant differences in postoperative outcomes including time to first bowel movement and time to tolerating diet. There was also no significant difference in overall complication rate; patients with MBP had 31/70 (44%) complications while 2/10 (20%) of those without MBP had complications (p = 0.18)., Conclusion: There was no significant difference in perioperative measures and postoperative complications for patients who did not receive a mechanical bowel preparation. Our findings indicate that it is safe and warranted to perform a prospective, randomized study to better characterize the risks and benefits of preoperative bowel preparation for patients with myelomeningocele.

Previous studies have reported association of multiple preoperative factors predicting clinically significant prostate cancer with varying results. We assessed the predictive model using a combination of hormone profile, serum biomarkers, and patient characteristics in order to improve the accuracy of risk stratification of patients with prostate cancer. Data on 224 patients from our prostatectomy database were queried. Demographic characteristics, including age, body mass index (BMI), clinical stage, clinical Gleason score (GS) as well as serum biomarkers, such as prostate-specific antigen (PSA), parathyroid hormone (PTH), calcium (Ca), prostate acid phosphatase (PAP), testosterone, and chromogranin A (CgA), were used to build a predictive model of clinically significant prostate cancer using logistic regression methods. We assessed the utility and validity of prediction models using multiple 10-fold cross-validation. Bias-corrected area under the receiver operating characteristics (ROC) curve (bAUC) over 200 runs was reported as the predictive performance of the models. On univariate analyses, covariates most predictive of clinically significant prostate cancer were clinical GS (OR 5.8, 95% CI 3.1-10.8; P < 0.0001; bAUC = 0.635), total PSA (OR 1.1, 95% CI 1.06-1.2; P = 0.0003; bAUC = 0.656), PAP (OR 1.5, 95% CI 1.1-2.1; P = 0.016; bAUC = 0.583), and BMI (OR 1.064, 95% C.I. 0.998, 1.134; P < 0.056; bAUC = 0.575). On multivariate analyses, the most predictive model included the combination of preoperative PSA, prostate weight, clinical GS, BMI and PAP with bAUC 0.771 ([2.5, 97.5] percentiles = [0.76, 0.78]). Our model using preoperative PSA, clinical GS, BMI, PAP, and prostate weight may be a tool to identify individuals with adverse oncologic characteristics and classify patients according to their risk profiles., Competing Interests: CONFLICTS OF INTEREST None.

Purpose: Prostate cancers incite tremendous morbidity upon metastatic growth. We previously identified Asporin (ASPN) as a potential mediator of metastatic progression found within the tumor microenvironment. ASPN contains an aspartic acid (D)-repeat domain and germline polymorphisms in D-repeat-length have been associated with degenerative diseases. Associations of germline ASPN D polymorphisms with risk of prostate cancer progression to metastatic disease have not been assessed., Experimental Design: Germline ASPN D-repeat-length was retrospectively analyzed in 1,600 men who underwent radical prostatectomy for clinically localized prostate cancer and in 548 noncancer controls. Multivariable Cox proportional hazards models were used to test the associations of ASPN variations with risk of subsequent oncologic outcomes, including metastasis. Orthotopic xenografts were used to establish allele- and stroma-specific roles for ASPN D variants in metastatic prostate cancer., Results: Variation at the ASPN D locus was differentially associated with poorer oncologic outcomes. ASPN D14 [HR, 1.72; 95% confidence interval (CI), 1.05-2.81, P = 0.032] and heterozygosity for ASPN D13/14 (HR, 1.86; 95% CI, 1.03-3.35, P = 0.040) were significantly associated with metastatic recurrence, while homozygosity for the ASPN D13 variant was significantly associated with a reduced risk of metastatic recurrence (HR, 0.44; 95% CI, 0.21-0.94, P = 0.035) in multivariable analyses. Orthotopic xenografts established biologic roles for ASPN D14 and ASPN D13 variants in metastatic prostate cancer progression that were consistent with patient-based data., Conclusions: We observed associations between ASPN D variants and oncologic outcomes, including metastasis. Our data suggest that ASPN expressed in the tumor microenvironment is a heritable modulator of metastatic progression., (©2015 American Association for Cancer Research.)

Prostate cancer is a leading cause of cancer death in men due to the subset of cancers that progress to metastasis. Prostate cancers are thought to be hardwired to androgen receptor (AR) signaling, but AR-regulated changes in the prostate that facilitate metastasis remain poorly understood. We previously noted a marked reduction in secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) expression during invasive phases of androgen-induced prostate growth, suggesting that this may be a novel invasive program governed by AR. Herein, we show that SPARCL1 loss occurs concurrently with AR amplification or overexpression in patient-based data. Mechanistically, we demonstrate that SPARCL1 expression is directly suppressed by androgen-induced AR activation and binding at the SPARCL1 locus via an epigenetic mechanism, and these events can be pharmacologically attenuated with either AR antagonists or HDAC inhibitors. We establish using the Hi-Myc model of prostate cancer that in Hi-Myc/Sparcl1(-/-) mice, SPARCL1 functions to suppress cancer formation. Moreover, metastatic progression of Myc-CaP orthotopic allografts is restricted by SPARCL1 in the tumor microenvironment. Specifically, we show that SPARCL1 both tethers to collagen in the extracellular matrix (ECM) and binds to the cell's cytoskeleton. SPARCL1 directly inhibits the assembly of focal adhesions, thereby constraining the transmission of cell traction forces. Our findings establish a new insight into AR-regulated prostate epithelial movement and provide a novel framework whereby SPARCL1 in the ECM microenvironment restricts tumor progression by regulating the initiation of the network of physical forces that may be required for metastatic invasion of prostate cancer., (©2015 American Association for Cancer Research.)