BACKGROUND:The mechanisms underlying metastatic latency in renal cell carcinoma (RCC) remain poorly understood. METHODS:This study evaluated 2 large independent cohorts for differences in tumor biology between patients who developed metastases early (≤1 year after nephrectomy) and those with late onset (>3 years). RESULTS:In the discovery cohort (n = 161), late metastatic RCC was associated with clear cell histology (88.9% vs 78.7%), lower pathological stage (pT1-2; 40.3% vs 18.0%), and favorable histopathological features including low grade (40.0% vs 2.3%), less sarcomatoid (5.6% vs 21.8%), and reduced necrosis (37.7% vs 78.3%; all P < .02). Late metastatic RCC tumors exhibited increased angiogenesis (63.5% vs 19.4%) and reduced inflammation (78.8% vs 50.0%; all P < .02) profiles. Genomic driver analyses revealed comparable rates of PBRM1 and SETD2 loss in late and early metastatic RCC, while BAP1 loss was significantly less common in late metastatic RCC (7.5% vs 27.1%; P < .02). In multivariable models, BAP1/PBRM1/SETD2 status and tumor necrosis emerged as key discriminators of late metastatic RCCs. These findings were confirmed in the second cohort (n = 307). Late metastatic RCC was enriched for fatty acid oxidation and angiogenesis pathways, supporting a less aggressive phenotype. This was further evidenced by a lower engraftment rate in murine models (0% vs 36.5%; P < .001) and significantly longer overall survival from the time of metastasis (median survival doubled, P < .001). Interestingly, late metastatic RCC shared genomic and phenotypic features with RCC that metastasizes to the pancreas, suggesting a common underlying biology influencing both metastatic latency and pancreatic tropism. CONCLUSIONS:Overall, these findings advocate for recognition of late metastatic RCC because of its distinct biology and improved prognosis.

Background: Colorectal cancer (CRC) is now the leading cause of cancer-related deaths among young Americans. Our study aims to predict early-onset CRC (EOCRC) using machine learning (ML) and structured electronic health record (EHR) data for individuals under the screening age of 45. Methods: We identified a cohort of patients under 45 from the OneFlorida+ Clinical Research Consortium. Given the distinct pathology of colon cancer (CC) and rectal cancer (RC), we created separate prediction models for each cancer type with various ML algorithms. We assessed multiple prediction time windows (0, 1, 3, and 5 years) and ensured robustness through propensity score matching (PSM) to account for confounding variables. Model performance was assessed using established metrics. Additionally, we employed the Shapley Additive exPlanations (SHAP) to identify risk factors for EOCRC. Results: Our study yielded results, with Area Under the Curve (AUC) scores of 0.811, 0.748, 0.689, and 0.686 for CC prediction, and 0.829, 0.771, 0.727, and 0.721 for RC prediction at 0, 1, 3, and 5 years, respectively. Notably, predictors included immune and digestive system disorders, along with secondary cancers and underweight, prevalent in both CC and RC groups. Blood diseases emerged as prominent indicators of CC. Conclusion: This study highlights the potential of ML techniques in leveraging EHR data to predict EOCRC, offering valuable insights for potential early diagnosis in patients who are below the recommended screening age. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the UF CTSI Precision Health Initiative. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study has been approved and the requirement to obtain any informed consent has been waived by the University of Florida Institutional Review Board (protocol no. IRB202201561). The research does not involve greater than minimal risk for participation. Analyses only involve the secondary analysis of data that are either limited data sets or de-identified. Our research team has no direct contact with human subjects. All methods were carried out in accordance with relevant guidelines and regulations. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Acute kidney injury (AKI) is a sudden event that damages the kidney and disrupts normal function by various causes, such as ischemia, exposure to substances, or obstructions. With AKIs affecting 1 out of 5 hospitalized patients and their association with increased risk of chronic kidney disease (CKD), finding an effective treatment for AKIs is of vital importance. One possible treatment for AKIs could be found within the realm of progenitor cell therapy. Progenitor cells are currently used in the treatment of hematological diseases with the burgeoning information on their possible uses for other disorders. The purpose of this study was to determine whether there is a resident population of renal progenitor cells (RPCs) within the kidney and if these cells can be utilized as an effective treatment to mitigate aging AKI by decreasing inflammation through alteration of the M1:M2 macrophage ratio. This study utilized 75-78 weeks old C57BL/6J female mice to determine if RPCs can reduce the damage caused by ischemic reperfusion (IR)-induced AKI. Kidneys were harvested from young female (40 days old) mice and digested in collagenase type 1 to remove connective tissue. Cells were sorted by flow cytometry, positively selected for c-Kit using magnetic nanoparticles, and subsequently stained for Sca1 and Oct4. Aging female mice underwent renal IR injury (IRI) by clamping off the renal artery and vein for 27 minutes. Following reperfusion, the triple-positive cells were suspended in DMEM and injected into the kidney over the course of 8 minutes to reduce the possibility of pressure necrosis. A separate group of mice was injected with saline to serve as control. The mice were monitored for 3 days at which point kidney function was assessed and tissue harvested for biochemical analysis. Our results indicated an increase in inflammatory cytokines IL-17, NF-κB, and IL-6 in IRI mice which were mitigated with RPCs treatment along with an increase in anti-inflammatory marker IL-10. Furthermore, an increase in M1 macrophage markers was measured in IRI, and a trending increase in M2 macrophage markers in IRI animals treated with RPCs. The kidney function of IRI animals treated with RPC showed improvement compared to IRI control. In summary, we found a population of cells positive for three progenitor cell markers: c-Kit, Sca1, Oct4, and treating IRI aging female kidney with these cells reduced inflammatory markers along with an increase in kidney function, suggesting RPCs promote recovery from AKI by reducing inflammation. Grant Support: DK116591. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Supplementary Figure from Intratumoral Resolution of Driver Gene Mutation Heterogeneity in Renal Cancer Using Deep Learning

Introduction The Florida-California Cancer Research, Education, and Engagement (CaRE 2 ) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE 2 triad partnership. Methods CaRE 2 serves diverse populations in Florida and California using a “molecule to the community and back” model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. Results Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE 2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE 2 -related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE 2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. Conclusion The CaRE 2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

AbstractIntratumoral heterogeneity arising from tumor evolution poses significant challenges biologically and clinically. Dissecting this complexity may benefit from deep learning (DL) algorithms, which can infer molecular features from ubiquitous hematoxylin and eosin (H&E)–stained tissue sections. Although DL algorithms have been developed to predict some driver mutations from H&E images, the ability of these DL algorithms to resolve intratumoral mutation heterogeneity at subclonal spatial resolution is unexplored. Here, we apply DL to a paradigm of intratumoral heterogeneity, clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer. Matched IHC and H&E images were leveraged to develop DL models for predicting intratumoral genetic heterogeneity of the three most frequently mutated ccRCC genes, BAP1, PBRM1, and SETD2. DL models were generated on a large cohort (N = 1,282) and tested on several independent cohorts, including a TCGA cohort (N = 363 patients) and two tissue microarray (TMA) cohorts (N = 118 and 365 patients). These models were also expanded to a patient-derived xenograft (PDX) TMA, affording analysis of homotopic and heterotopic interactions of tumor and stroma. The status of all three genes could be inferred by DL, with BAP1 showing the highest sensitivity and performance within and across tissue samples (AUC = 0.87–0.89 on holdout). BAP1 results were validated on independent human (AUC = 0.77–0.84) and PDX (AUC = 0.80) cohorts. Finally, BAP1 predictions correlated with clinical outputs such as disease-specific survival. Overall, these data show that DL models can resolve intratumoral heterogeneity in cancer with potential diagnostic, prognostic, and biological implications.Significance:This work demonstrates the potential for deep learning analysis of histopathologic images to serve as a fast, low-cost method to assess genetic intratumoral heterogeneity.See related commentary by Song et al., p. 2672

You have accessJournal of UrologyCME1 May 2022MP25-12 ROBOTIC BUCCAL GRAFT URETEROPLASTY WITHOUT URETERAL REST Shellee Ogawa, Wesley Baas, Kushan Radadia, Alexander Parker, Kefu Du, Eric Kim, Robert Figenshau, and Gregory Murphy Shellee OgawaShellee Ogawa More articles by this author , Wesley BaasWesley Baas More articles by this author , Kushan RadadiaKushan Radadia More articles by this author , Alexander ParkerAlexander Parker More articles by this author , Kefu DuKefu Du More articles by this author , Eric KimEric Kim More articles by this author , Robert FigenshauRobert Figenshau More articles by this author , and Gregory MurphyGregory Murphy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002568.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Robotic buccal graft ureteroplasty (RBGU) is a promising technique for ureteral reconstruction with growing evidence to support its use. Ureteral rest prior to ureteral reconstruction is often advocated by experts in the field. We describe our experience with RBGU at our institution without ureteral rest, focusing on perioperative management and outcomes to add to the growing body of literature for this approach. METHODS: We retrospectively reviewed patients who underwent RBGU at our institution from March 2018 to September 2021. Demographic information, operative details, and complications were recorded. All strictures were initially evaluated with retrograde pyelography and, when feasible, ureteroscopy to delineate stricture length and location. In all patients, a 6F ureteral stent was left in place preoperatively to improve the quality of the ureteral plate. After surgery, a stent was left in place for six weeks. Removal was initially done in clinic but is now done in the OR with retrograde pyelography. Patients were followed with renal ultrasound and, if necessary, renal scintigraphy. RESULTS: Seventeen patients were identified with a median age of 58 years (IQR 43-64). Median stricture length was 4.7 cm (range 3-7 cm). Median length of follow up was 13 months (IQR 5-20.5). All but one stent was removed at six weeks; the exception was due to a persistent leak on retrograde pyelography which resolved by ten weeks. Complications included one stricture recurrence/urinoma, one bowel obstruction which resolved with conservative measures, two UTIs and one readmission for pain control. Two patients had recurrent stone episodes requiring ureteroscopy. Overall success rate, defined as lack of stricture recurrence, was 93.3%. CONCLUSIONS: RBGU is a safe and effective procedure for management of complex ureteral strictures. Despite emerging evidence in support of ureteral rest, our series demonstrates low rates of recurrence without ureteral rest with moderate follow up. We believe preoperative stenting is not inferior to ureteral rest and is better tolerated by patients. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e432 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shellee Ogawa More articles by this author Wesley Baas More articles by this author Kushan Radadia More articles by this author Alexander Parker More articles by this author Kefu Du More articles by this author Eric Kim More articles by this author Robert Figenshau More articles by this author Gregory Murphy More articles by this author Expand All Advertisement PDF downloadLoading ...

OBJECTIVE:To evaluate if decreasing postop abx prophylaxis affects UTI and wound infection rates in patients following urethroplasty. METHODS:A retrospective review of patients who underwent urethroplasty from 9/2017 - 3/2020 by a single surgeon was performed. All patients received urine culture specific perioperative IV abx prior to urethroplasty and kept a urethral catheter for 3 weeks postop. Patients undergoing a urethroplasty from 9/2017 to 12/2018 received extended postop abx prophylaxis for 3 weeks until catheter removal (Group 1). Patients from 12/2018 to 3/2020 received abx for 3 days around catheter removal (Group 2). UTIs, abx complications, and wound infections between groups were evaluated. UTIs were defined as a positive urine culture or reported lower urinary tract symptoms/fevers treated with empiric abx. RESULTS:120 patients underwent urethroplasty. Group 1 consisted of 60 patients with mean age of 51.9 years and mean stricture length of 3.6 cm. Group 2 had 60 patients with mean age of 53.1 years and mean stricture length of 3.8 cm. 10 patients had UTIs after urethroplasty. There was no significant difference in UTI (6.7% vs 11.7%; P = 0.529) or wound infection rates (3.3% vs 1.7%;' P = 1.000) between the two groups. CONCLUSION:Extended postoperative antibiotic prophylaxis does not appear to significantly affect UTI or wound infection rates following urethroplasty. The retrospective nature of the study has limitations, however, this is the first comparison of two different antibiotic administration protocols to our knowledge.

Pather, Keouna MD; Hacker, Shoshana MD, FACS; Guerrier, Christina MBA; Mobley, Erin M. PhD, MPH; Esma, Rhemar MD; Baskovich, Brett W. MD; Parker, Alexander S. MS, PhD; Vigal, Kimberly MHA; Awad, Ziad T. MD, FACS Author Information

Background: The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown.Methods: We analyzed 420 ccRCC patients from The Cancer Genome Atlas (TCGA). Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results: The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR=1.6, p=0.0037) and SSIGN score (OR=1.9, p=0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes.Conclusions: These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

Abstract Introduction: The Florida-California CaRE2 Health Equity Center was established in 2018 to address cancer health disparities in Black and Latino communities through innovative translational research in cancers of high mortality. Long term, the CaRE2 Center aims to: 1) reduce cancer disparities in Blacks and Latinos; 2) train and increase the pool of underrepresented Black and Latino scientists conducting health disparity research; 3) increase research capacity at a historically minority serving institution (FAMU); and 4) increase cancer disparity research at UF and USC-NCCC. Two full projects and one pilot project focused on prostate and pancreatic cancers are supported by several cores, including the Tissue Modelling Core. The projects provide research training opportunities across the triad partnership to underrepresented minority students, post-doctoral fellows, and early stage investigators. In this presentation, we describe how the developmental evaluation model (DEM) guided assessment of the CaRE2 Center’s objectives. Methods: The CaRE2 Center Planning and Evaluation Core (PEC) has conducted continuous planning, evaluation and tracking of the partnership activities to ensure the successful achievement of the aims proposed for the Center, its cores, and research projects. The achievement of program goals has been guided by the Provus’ DEM, which focuses on evaluating performance and improving program function. Its premise is that evaluation is: (1) a constructive activity; (2) a dynamic ongoing process; and (3) includes comparison of actual performance with standards and expectations. Each PEC member was assigned as a liaison to one or more of the Center’s cores and research projects. Using a tabular format, each liaison drafted an evaluation plan to guide assessment of their proposed objectives. The liaisons participated in regularly scheduled core and project meetings during the year one of the Center. Results: Each liaison discussed and solicited feedback related to the comprehensive draft evaluation plans. Using a table format, a list of the aims, outcomes, and corresponding benchmarks was presented alongside PEC feedback. PEC feedback provided: (1) evidence of if and how the benchmark was met; and (2) if achieving a benchmark was still in progress. If a benchmark had not been achieved, PEC requested additional information or suggested evaluation metrics to assess future attainment. Each report also included a summary statement in which PEC provided commendations, suggestions, weaknesses, and/or guidance for future reports. PEC provided this feedback formatively and individually to core and research projects quarterly and via a cumulative annual progress report. A comprehensive overview of all core and research project formative reports was sent to the Administrative Core for continuous quality improvement. The Center exceeded most of the benchmarks for year one. Conclusion: The DEM has been instrumental in guiding present and future attainment of the CaRE2 Center objectives. Citation Format: Linda S Behar-Horenstein, Joyce Richey, Alexander Parker, Folakemi T Odedina, Nissa Askins. Developmental evaluation model for the Florida-California CaRE2 Health Equity Center [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D031.

Emergency laparotomy in patients over the age of 80 is associated with high morbidity and mortality. Accurate risk prediction in this patient population is desirable. Sarcopenia has been shown to be associated with outcome in multiple clinical settings and the psoas major muscle as measured on computed tomography (CT) imaging has been demonstrated as a marker of sarcopenia. We aim to assess the use of psoas major measurement on pre-operative CT as a prognostic indicator in over-80s undergoing emergency laparotomy and compare this measurement to P-POSSUM.

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy III (MP67)1 Apr 2020MP67-20 PREOPERATIVE PROSTATE MRI DOES NOT IMPACT SURGICAL OUTCOMES OF RADICAL PROSTATECTOMY Nicholas Pickersgill*, Joel Vetter, Gerald Andriole, Shilpa Argade, Brandon Wahba, Grant Henning, Alexander Parker, and Eric Kim Nicholas Pickersgill*Nicholas Pickersgill* More articles by this author , Joel VetterJoel Vetter More articles by this author , Gerald AndrioleGerald Andriole More articles by this author , Shilpa ArgadeShilpa Argade More articles by this author , Brandon WahbaBrandon Wahba More articles by this author , Grant HenningGrant Henning More articles by this author , Alexander ParkerAlexander Parker More articles by this author , and Eric KimEric Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000947.020AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Multiparametric magnetic resonance imaging (MRI) of the prostate has been increasingly utilized for staging of prostate cancer (PCa). Studies have suggested that benefits of pre-prostatectomy MRI include risk stratification and operative planning. However, the marginal benefit that preoperative MRI confers on surgical outcomes has not been well defined. We reviewed our institutional experience of prostatectomy with versus without preoperative MRI. METHODS: We identified patients at our tertiary care institution who underwent prostatectomy for PCa between January 2012 and December 2017 (n=1044). Using propensity scoring analysis, patients who underwent preoperative MRI were matched 1:1 to patients who did not receive preoperative MRI (based on age, race, body-mass index (BMI), comorbidity (Charlson comorbidity index), PSA, biopsy Gleason score, and operating surgeon). The final matched cohort included 285 patients with preoperative MRI and 285 patients without. Multivariate regression analysis was performed for operative time, estimated blood loss (EBL), lymph node yield, complication rates, and positive surgical margin. RESULTS: There were no significant differences in operative time, EBL, positive surgical margin rate, lymph node yield, or complication rate between the two cohorts. When controlling for all measured variables, multivariate analysis demonstrated that preoperative MRI was not predictive of any of the measured surgical outcomes. Significant comorbidity (CCI≥3) was the sole predictor of perioperative complications (p=0.015). Increasing comorbidity and biopsy Gleason score predicted increased lymph node yield (p<0.001). The probability of positive surgical margin was significantly associated with increasing preoperative PSA (OR 1.05, p<0.001). BMI was the sole predictor of operative time (p=0.016) and EBL (p=0.001). CONCLUSIONS: While prostate MRI has a role in PCa diagnosis and staging, preoperative MRI does not impact technical prostatectomy outcomes in our institutional experience. Our findings do not support the routine use of preoperative MRI for surgical planning in patients with clinically localized PCa. Studies investigating the effects of preoperative MRI on long-term patient self-reported outcomes following prostatectomy are needed. Source of Funding: No funding was provided specifically for this study. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1033-e1033 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicholas Pickersgill* More articles by this author Joel Vetter More articles by this author Gerald Andriole More articles by this author Shilpa Argade More articles by this author Brandon Wahba More articles by this author Grant Henning More articles by this author Alexander Parker More articles by this author Eric Kim More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyPenile & Testicular Cancer: Penile & Testicular Cancer III (MP76)1 Apr 2020MP76-08 LEYDIG CELL TUMOR OF THE TESTIS: PATHOLOGICAL CHARACTERISTICS AND TREATMENT PATTERNS FROM THE NATIONAL CANCER DATABASE Julie Nguyen*, Kyle Hickey, Vishal Patel, Michael Cookson, Kelly Stratton, Brian Cross, Alexander Parker, and Sanjay Patel Julie Nguyen*Julie Nguyen* More articles by this author , Kyle HickeyKyle Hickey More articles by this author , Vishal PatelVishal Patel More articles by this author , Michael CooksonMichael Cookson More articles by this author , Kelly StrattonKelly Stratton More articles by this author , Brian CrossBrian Cross More articles by this author , Alexander ParkerAlexander Parker More articles by this author , and Sanjay PatelSanjay Patel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000962.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Leydig cell tumors are a rare type of sex-cord stromal tumor that comprise 1-3% of all testicular neoplasms. Due to its rarity, limited data is available to guide treatment and management. Using the National Cancer Data Base (NCDB), we sought to determine the association of pathological characteristics, retroperitoneal lymph node dissection (RPLND), and overall survival. METHODS: We identified 309 patients from the National Cancer Database diagnosed with Leydig cell tumor from 2004 to 2015. Patients who did not receive orchiectomy were excluded. Pathologic characteristics and use of RPLND were determined. Overall survival was analyzed by Kaplan-Meier method for tumor size, pathologic tumor stage, and AJCC stage. RESULTS: Of the 66,042 cases of testicular cancer between 2004 and 2015, 309 (0.47%) were Leydig cell tumors. The median patient age of diagnosis was 47 years (IQR, 34-59) with a median follow-up of 51 months. Of the 309 patients, 75.7% were White, 19.1% were Black, and 5.2% were made up of other ethnic backgrounds. The majority of patients were Stage I (94.22%), with the remaining patients in Stage II (2.89%) and Stage III (2.89%). OS at 3 years was 97.1% (95% CI, 93.7-98.7), 60% (95% CI, 12.6-88.2), and 33.3% (95% CI, 4.61-67.6), respectively (p < 0.0001). Median tumor size was 1.8 cm (IQR, 0.9 – 3.5). OS at 5 years for tumor sizes <=2.5 cm, >2.5 cm to <=5 cm, and >5 cm were 96.4% (95% CI, 91.4-98.5), 87.5% (95% CI, 73.6-94.3) and 73.5% (95% CI, 56.2-84.8), respectively (p< 0.0001). In patients with pTis/pT1, the 5 year OS is 96.1% (95% CI, 91.2-98.3) compared with pT2 OS of 45.9% (95% CI, 20.0-68.8) and pT3 OS of 40% (95% CI, 5.2%-75.3%) (p< 0.0001). Two of 7 patients with positive margins died. Twenty-seven patients received RPLND, of which 10 patients were node positive. The 3 year OS for patients who were N0 and N+ at the time of RPLND was 92.3% (95% CI, 56.6-98.9) and 50% (95% CI,11.1-80.4), respectively (p< 0.05). Four of 6 patients with metastatic disease died within 2 and 19 months. CONCLUSIONS: Larger tumor size and higher pathological T stage were indicators of poorer overall survival in patients with Leydig cell tumors. Patients who received a retroperitoneal lymph node dissection had worse outcomes compared to those who did not. Further investigation is required to determine the optimal treatment for patients with these tumors. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1154-e1154 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Julie Nguyen* More articles by this author Kyle Hickey More articles by this author Vishal Patel More articles by this author Michael Cookson More articles by this author Kelly Stratton More articles by this author Brian Cross More articles by this author Alexander Parker More articles by this author Sanjay Patel More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy (MP43)1 Apr 2020MP43-01 EVALUATING HEALTHCARE UTILIZATION OF ALPHA-BLOCKER FOR MEDICAL EXPULSIVE THERAPY IN SYMPTOMATIC PATIENTS WITH URETERAL STONES Alexander Parker*, Alana Desai, Shilpa Argade, Joel Vetter, Matt Keller, Margaret Olsen, Alethea Paradis, and Ramakrishna Venkatesh Alexander Parker*Alexander Parker* More articles by this author , Alana DesaiAlana Desai More articles by this author , Shilpa ArgadeShilpa Argade More articles by this author , Joel VetterJoel Vetter More articles by this author , Matt KellerMatt Keller More articles by this author , Margaret OlsenMargaret Olsen More articles by this author , Alethea ParadisAlethea Paradis More articles by this author , and Ramakrishna VenkateshRamakrishna Venkatesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000898.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Alpha-blocker medical expulsive therapy (MET) is widely utilized in the treatment of ureteral stones though its effectiveness is questionable. With increasing burden of urolithiasis on US healthcare, the utilization effects of α-blocker therapy have not been elucidated. We studied the effects of α-blocker MET in reducing surgical intervention, imaging, adverse events, ER visits, and cost up to 3 months. METHODS: Patients were selected from a US national commercial claims database between 2011 and 2016 based on prescription of α-blocker for a primary diagnosis of ureteral stone in an emergency room (ER), urgent care, outpatient, or inpatient hospital setting. We identified 58568 patients with and 78653 patients without prescription for alpha-blocker. Evaluation was performed at 30 days and 90 days after diagnosis of a ureteral stone event to determine rate of surgical intervention, number and type of follow-up imaging studies, adverse events, ER visits, and total medical claims cost. Multivariable linear and logistic regression models were used to test associations between outcome variables and the use of MET. RESULTS: α-blockers were prescribed to 43% of patients with ureteral stones for median length of 14 days. At 30-days after index stone event, 20.6% MET vs. 20.1% non- MET (p<0.001, OR=1.07) underwent a surgical procedure, 40% MET vs. 32% non-MET (p<0.001, OR=1.46) had a follow-up imaging study (KUB, CT or US scan) and 20% MET vs. 16% non-MET (p<0.001, OR=1.36) presented to the ER. Total medical claims cost at 30 days was $3860 (IQR=$2117–7393) for MET compared to $3290 (IQR=$1395-6839) for non-MET patients (p<0.01). At 90-days after index stone event 24% MET vs. 23% non-MET (p < 0.001, OR = 1.08) underwent a surgical procedure, 46% MET vs. 38% non-MET (p < 0.001, OR = 1.417) had a follow-up imaging study, and 24% MET vs. 21% non-MET (p < 0.001, OR = 1.261) presented to the ER. 90-day total medical claims cost was $4597 (IQR=$2518-9519) for MET vs. $4137 (IQR= $1877-9112) for non-MET patients (p < 0.001). UTI and sepsis events were infrequent in both groups. CONCLUSIONS: In this largest cohort of patients who were prescribed α-blocker for ureteral stone treatment there was no reduction in the number of surgical procedures at 3 months. However, there was an increase in the subsequent ER visits, follow up imaging studies, and total cost to the health system. These results should be factored along with questionable efficacy of α-blocker for optimal utilization of resources for a common and expensive stone disease. Source of Funding: Midwest Stone Institute, St. Louis, MO © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e647-e647 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Parker* More articles by this author Alana Desai More articles by this author Shilpa Argade More articles by this author Joel Vetter More articles by this author Matt Keller More articles by this author Margaret Olsen More articles by this author Alethea Paradis More articles by this author Ramakrishna Venkatesh More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract Approximately 10%‐20% of patients with clinically localized clear cell renal cell carcinoma (ccRCC) at time of surgery will subsequently experience metastatic progression. Although considerable progression was seen in the systemic treatment of metastatic ccRCC in last 20 years, once ccRCC spreads beyond the confines of the kidney, 5‐year survival is less than 10%. Therefore, significant clinical advances are urgently needed to improve overall survival and patient care to manage the growing number of patients with localized ccRCC. We comprehensively evaluated expression of 388 candidate genes related with survival of ccRCC by using TCGA RNAseq (n = 515), Total Cancer Care (TCC) expression array data (n = 298), and a well characterized Moffitt RCC cohort (n = 248). We initially evaluated all 388 genes for association with overall survival using TCGA and TCC data. Eighty‐one genes were selected for further analysis and tested on Moffitt RCC cohort using NanoString expression analysis. Expression of nine genes (AURKA, AURKB, BIRC5, CCNE1, MK167, MMP9, PLOD2, SAA1, and TOP2A) was validated as being associated with poor survival. Survival prognostic models showed that expression of the nine genes and clinical factors predicted the survival in ccRCC patients with AUC value: 0.776, 0.821 and 0.873 for TCGA, TCC and Moffitt data set, respectively. Some of these genes have not been previously implicated in ccRCC survival and thus potentially offer insight into novel therapeutic targets. Future studies are warranted to validate these identified genes, determine their biological mechanisms and evaluate their therapeutic potential in preclinical studies.