214 results on '"Peter E. Clark"'
Search Results
2. Prognostic value of galectin-1 and galectin-3 expression in localized urothelial bladder cancer
- Author
-
Jason Zhu, Chad Livasy, Erin E. Donahue, James T. Symanowski, Claud M. Grigg, Landon C. Brown, Justin T. Matulay, James T. Kearns, Derek Raghavan, Earle F. Burgess, and Peter E. Clark
- Subjects
Reproductive Medicine ,Urology - Published
- 2023
- Full Text
- View/download PDF
3. Association of Surgical Approach and Urinary Diversion in Radical Cystectomy for Bladder Cancer With Costs and Readmission: Results From a Large Private Health Insurance Cohort
- Author
-
Miguel Rodriguez-Homs, Rodrigo Rodrigues Pessoa, Badrinath Konety, Boris Gershman, Peter E. Clark, Michael Bronsert, Thomas W. Flaig, Sarah E. Tevis, Granville Lloyd, Jeffrey C. Morrison, and Simon P. Kim
- Subjects
Urology - Published
- 2022
- Full Text
- View/download PDF
4. Racial and Socioeconomic Disparities in MRI-Fusion Biopsy Utilization to Assess for Prostate Cancer
- Author
-
Emily, Roebuck, Wei, Sha, Caroline D, Lu, Caroline, Miller, Earle F, Burgess, Claud M, Grigg, Jason, Zhu, Kris E, Gaston, Stephen B, Riggs, Justin T, Matulay, Peter E, Clark, and James T, Kearns
- Subjects
Image-Guided Biopsy ,Male ,Socioeconomic Factors ,Urology ,Humans ,Prostatic Neoplasms ,Magnetic Resonance Imaging ,Retrospective Studies - Abstract
To evaluate whether racial disparities in MRI-Bx usage persisted after correction for socioeconomic, demographic, and clinical factors.This is a retrospective cohort study of patients who received either MRI-Bx or systematic biopsy (SB) within a single academic medical center between January 2018 - June 2020. For each patient, socioeconomic variables including household income, education, percent below poverty, and unemployment were estimated using 2015 American Community Survey census-tract level data. Chi-square analysis was used to examine differences in clinical and demographic characteristics between the two groups. The Benjamini-Hochberg procedure was used to control false discovery rate (FDR) for multiple testing.Eighteen percent of Black men (53/295) received MRI-Bx while 41% (228/561) of white men received MRI-Bx. Patients coming from highly impoverished areas were less likely to receive MRI-Bx, 25% vs 75%, respectively. In multivariate analysis, race remained significantly different across MRI-Bx and SB groups. Clinical factors including family history, DRE, BMI, and prostate volume were not significantly different between patients receiving MRI-Bx and SB.Black men are less likely to receive MRI-Bx than white men, even after adjusting for clinical and socioeconomic characteristics. Further work is necessary to identify and study methods to increase equity in PCa diagnostic testing.
- Published
- 2022
- Full Text
- View/download PDF
5. GRade, Age, Nodes, and Tumor (GRANT) compared with Leibovich score to predict survival in localized renal cell carcinoma: A nationwide study
- Author
-
Simon Juul, Frede Donskov, Peter E Clark, Lars Lund, and Nessn H Azawi
- Subjects
overall survival ,Urology ,Humans ,Neoplasm Recurrence, Local ,Leibovich ,Prognosis ,Carcinoma, Renal Cell ,Nephrectomy ,disease free survival ,RCC ,Kidney Neoplasms ,Retrospective Studies ,GRANT - Abstract
Objective To examine the performance of Leibovich score versus GRade, Age, Nodes, and Tumor score in predicting disease recurrence in renal cell carcinoma. Methods In total, 7653 patients diagnosed with renal cell carcinoma from 2010 to 2018 were captured in the nationwide DaRenCa database; 2652 underwent radical or partial nephrectomy and had full datasets regarding the GRade, Age, Nodes, and Tumor score and Leibovich score. Discrimination was assessed with a Cox regression model. The results were evaluated with concordance index analysis. Results Median follow-up was 40 months (interquartile range 24-56). Recurrence occurred in 17%, and 15% died. A significant proportion of patients (36%) had missing data for the calculation of the Leibovich score. Among 1957 clear cell renal cell carcinoma patients the distribution of GRade, Age, Nodes, and Tumor score of 0, 1, 2, or 3/4 was 21%, 56%, 21% and 1.4%, respectively, and for Leibovich score of low/intermediate/high this was 47%, 36% and 18%, respectively. A similar distribution was seen in 655 non-clear cell patients. Both Leibovich and GRade, Age, Nodes, and Tumor scores performed well in predicting outcomes for the favorable patient risk groups. The Leibovich score was better at predicting recurrence-free survival (concordance index 0.736 versus 0.643), but not overall survival (concordance index 0.657 versus 0.648). Similar results were obtained in non-clear cell renal cell carcinoma. Conclusion GRade, Age, Nodes, and Tumor and Leibovich scores were validated in clear cell and non-clear cell renal cell carcinoma. Leibovich score outperformed the GRade, Age, Nodes, and Tumor score in predicting recurrence-free survival and should remain the standard approach to risk stratify patients during follow-up when all data are available.
- Published
- 2022
- Full Text
- View/download PDF
6. Surgeon-administered Transversus Abdominis Plane (TAP) Block is Associated With Decreased Opioid Usage and Length of Stay Following Radical Cystectomy
- Author
-
Emily Roebuck, Hamza Beano, Myra Robinson, Daniel Edwards, William M. Worrilow, Alexander Sinks, Kris E. Gaston, Peter E. Clark, and Stephen B. Riggs
- Subjects
Analgesics, Opioid ,Surgeons ,Pain, Postoperative ,Urology ,Humans ,Length of Stay ,Cystectomy ,Abdominal Muscles ,Retrospective Studies - Abstract
To study the effect of surgeon-administered Transversus Abdominis Plane block (sTAP) on opioid usage and length of stay (LOS).Starting in April 2018, two surgeons at our institution gradually introduced sTAP for radical cystectomy (RC) patients. We performed a retrospective observational cohort analysis of RC patients catalogued in a prospectively maintained database using the Enhanced Recovery After Surgery Interactive Auditing System. Two surgeons adopted the sTAP block technique in April 2018. We included patients undergoing RC for bladder malignancy under Enhanced Recovery After Surgery protocol between January 2017 and August 2020. Primary outcomes included LOS, and postoperative day (POD) 0-3 total opioids consumption measured by morphine milligram equivalents (MME). Multivariable linear or logistic models evaluated the association of TAP with outcomes while controlling for potential confounders.Among 178 patients included in analysis, 84 patients underwent sTAP block and 94 did not. Multivariable analysis demonstrated significantly lower POD 0-3 total opioid usage (106.4 vs 192.2 MME, P = .004), and mean LOS (5.6 vs 7.7 days, P.001) among the sTAP group.sTAP appears to be an effective adjunct to RC care associated with improved LOS, and POD 0-3 opioid consumption. Further studies are needed to optimize TAP block technique and anesthetic composition.
- Published
- 2022
- Full Text
- View/download PDF
7. Renal Mass Biopsy Mandate Is Associated With Change in Treatment Decisions
- Author
-
Alexander Sinks, Caroline Miller, Hailey Holck, Laurel Zeng, Kris Gaston, Stephen Riggs, Justin Matulay, Peter E. Clark, and Ornob Roy
- Subjects
Urology - Published
- 2023
- Full Text
- View/download PDF
8. Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry
- Author
-
Fei Chen, Ravi K. Madduri, Alex A. Rodriguez, Burcu F. Darst, Alisha Chou, Xin Sheng, Anqi Wang, Jiayi Shen, Edward J. Saunders, Suhn K. Rhie, Jeannette T. Bensen, Sue A. Ingles, Rick A. Kittles, Sara S. Strom, Benjamin A. Rybicki, Barbara Nemesure, William B. Isaacs, Janet L. Stanford, Wei Zheng, Maureen Sanderson, Esther M. John, Jong Y. Park, Jianfeng Xu, Ying Wang, Sonja I. Berndt, Chad D. Huff, Edward D. Yeboah, Yao Tettey, Joseph Lachance, Wei Tang, Christopher T. Rentsch, Kelly Cho, Benjamin H. Mcmahon, Richard B. Biritwum, Andrew A. Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Thomas A. Sellers, Kosj Yamoah, Adam B. Murphy, Dana C. Crawford, Alpa V. Patel, William S. Bush, Melinda C. Aldrich, Olivier Cussenot, Gyorgy Petrovics, Jennifer Cullen, Christine M. Neslund-Dudas, Mariana C. Stern, Zsofia Kote-Jarai, Koveela Govindasami, Michael B. Cook, Anand P. Chokkalingam, Ann W. Hsing, Phyllis J. Goodman, Thomas J. Hoffmann, Bettina F. Drake, Jennifer J. Hu, Jacob M. Keaton, Jacklyn N. Hellwege, Peter E. Clark, Mohamed Jalloh, Serigne M. Gueye, Lamine Niang, Olufemi Ogunbiyi, Michael O. Idowu, Olufemi Popoola, Akindele O. Adebiyi, Oseremen I. Aisuodionoe-Shadrach, Hafees O. Ajibola, Mustapha A. Jamda, Olabode P. Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, James E. Mensah, Halimatou Diop, Stephen K. Van Den Eeden, Pascal Blanchet, Jay H. Fowke, Graham Casey, Anselm J. Hennis, Alexander Lubwama, Ian M. Thompson, Robin Leach, Douglas F. Easton, Michael H. Preuss, Ruth J. Loos, Susan M. Gundell, Peggy Wan, James L. Mohler, Elizabeth T. Fontham, Gary J. Smith, Jack A. Taylor, Shiv Srivastava, Rosaline A. Eeles, John D. Carpten, Adam S. Kibel, Luc Multigner, Marie-Élise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Eric A. Klein, Caroline Andrews, Timothy R. Rebbeck, Laurent Brureau, Stefan Ambs, Todd L. Edwards, Stephen Watya, Stephen J. Chanock, John S. Witte, William J. Blot, J. Michael Gaziano, Amy C. Justice, David V. Conti, Christopher A. Haiman, University of Southern California (USC), Keck School of Medicine [Los Angeles], Centre de Recherche pour les Pathologies Prostatiques [Paris] (CeRePP), Sorbonne Université (SU), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre de recherche en épidémiologie et santé des populations (CESP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
- Subjects
Prostate cancer ,MESH: Humans ,Urology ,MESH: Genetic Predisposition to Disease ,MESH: Black People ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,MESH: Male ,Polygenic risk score ,African ancestry ,MESH: Risk Factors ,MESH: Prostatic Neoplasms ,MESH: Genome-Wide Association Study ,Susceptibility loci ,Aggressive prostate cancer - Abstract
Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.Design, setting, and participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.Outcome measurements and statistical analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.Results and limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4).Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry.Patient summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.
- Published
- 2023
- Full Text
- View/download PDF
9. Association of 5-Alpha Reductase Inhibitor Use with Prostate Specific Antigen Level at the Time of Urology Referral in a Retrospective Cohort at a Large, Integrated Health Care System
- Author
-
James T. Kearns, Jason Zhu, Stephen B. Riggs, Kris E. Gaston, Timothy Hetherington, Claud Grigg, Earle F. Burgess, William E. Anderson, Justin T. Matulay, and Peter E. Clark
- Subjects
medicine.medical_specialty ,Referral ,business.industry ,Urology ,Retrospective cohort study ,Reductase ,urologic and male genital diseases ,medicine.disease ,Prostate-specific antigen ,5 Alpha-Reductase Inhibitor ,Prostate cancer ,Concomitant ,Health care ,medicine ,business - Abstract
Introduction:5-Alpha reductase inhibitor (5-ARI) use leads to a 50% decline in serum prostate specific antigen (PSA) without a concomitant decrease in prostate cancer (PCa) risk. We hypothe...
- Published
- 2021
- Full Text
- View/download PDF
10. Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-Up: AUA Guideline: Part I
- Author
-
Robert G. Uzzo, Jose A. Karam, Steven C. Campbell, Peter E. Clark, Lesley Souter, and Sam S. Chang
- Subjects
Ablation Techniques ,Counseling ,medicine.medical_specialty ,Evidence-Based Medicine ,Adult patients ,medicine.diagnostic_test ,business.industry ,Urology ,medicine.medical_treatment ,Thermal ablation ,Cancer ,Antineoplastic Agents ,Guideline ,medicine.disease ,Nephrectomy ,Kidney Neoplasms ,Biopsy ,medicine ,Renal mass ,Humans ,business ,Kidney cancer - Abstract
This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article.Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.
- Published
- 2021
- Full Text
- View/download PDF
11. Genomic analysis of response to bacillus Calmette-Guérin (BCG) treatment in high-grade stage 1 bladder cancer patients
- Author
-
R. Tucker Burks, Cory Brouwer, Justin T. Matulay, Connor Frasier, Aaron Hartman, David M. Foureau, James T. Kearns, Earle F. Burgess, Stephen B. Riggs, Peter E. Clark, Jason Zhu, Claud Grigg, Nury Steuerwald, J. Alexa Sanders, and Kris E. Gaston
- Subjects
Oncology ,S100A7 ,medicine.medical_specialty ,Bladder cancer ,business.industry ,Urology ,Standard treatment ,Genomics ,medicine.disease ,DNA sequencing ,MSH6 ,Reproductive Medicine ,Downregulation and upregulation ,Internal medicine ,medicine ,Original Article ,Stage (cooking) ,business - Abstract
Background Intravesical bacillus Calmette-Guerin (BCG) therapy is standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) but overall efficacy is low, and no reliable predictive biomarkers currently exist to refine patient selection. We performed genomic analysis on high-grade (HG) T1 NMIBCs to determine if response to therapy is predicted by certain mutational and/or expressional changes. Methods Patients with HG T1 NMIBC treated with induction BCG were stratified by response into durable and non-durable responders. Baseline tumor samples were subjected to targeted DNA sequencing and whole-exome RNAseq. Genomic variants differing significantly between response groups were analyzed using Ingenuity Pathway Analysis (IPA) software. Variant selection was refined to target potential biomarker candidates for responsiveness to BCG. Results Among 42 patients, the median follow-up was 51.7 months and 40.5% (n=17) were durable BCG responders. Deleterious mutations in the RNA sequence of JCHAIN, S100A7, CLEC2B, and ANXA10 were more common in non-durable responders. Mutations in MCL1 and MSH6 detected on targeted sequencing were more commonly found in durable responders. Of all deleterious DNA and RNA mutations identified, only MCL1 was significantly associated with longer recurrence free survival (RFS) (P=0.031). Conclusions Differences in the genomic profiles of HG T1 NMIBC tumors exist between those who show durable response to BCG and those who do not. Using pathway analysis, those differences imply upregulation of several interconnected inflammatory pathways among responders. Specific variants identified here, namely MCL1, are candidates for further study and, if clinically validated, may serve as useful biomarkers in the future.
- Published
- 2021
- Full Text
- View/download PDF
12. Demographic and Socioeconomic Factors Associated with Urinary Stone Disease Management in a Large Urban US Population
- Author
-
Cameron Futral, James T. Kearns, Rupali Bose, Ornob P Roy, Sagar R. Patel, Caroline Miller, and Peter E. Clark
- Subjects
Male ,medicine.medical_specialty ,Social Determinants of Health ,Urology ,Urinary stone ,Population ,030232 urology & nephrology ,Insurance Claim Review ,03 medical and health sciences ,0302 clinical medicine ,Urolithiasis ,Lithotripsy ,Internal medicine ,North Carolina ,medicine ,Humans ,Healthcare Disparities ,education ,Socioeconomic status ,Demography ,Health Services Needs and Demand ,education.field_of_study ,business.industry ,Surgical care ,Urban Health ,Retrospective cohort study ,Middle Aged ,Patient Acceptance of Health Care ,Patient Care Management ,Socioeconomic Factors ,030220 oncology & carcinogenesis ,Urologic Surgical Procedures ,Female ,business ,Urinary stone disease - Abstract
To determine the influence of socioeconomic parameters on urinary stone surgeries.A retrospective cohort study analyzed patients undergoing urolithiasis surgery in our community network hospital in North Carolina from 2005-2018.Of 7731 patients, 2160 (28%), 5,174 (67%), and 397 (5%) underwent SWL, URS, and PCNL, respectively. A higher proportion of Whites underwent URS (67%) and SWL (74%) than PCNL (56%); whereas a larger percentage of Blacks underwent PCNL (24%) than URS (20%) and SWL (15%) groups (P.001). Private insurance payers were greater in the SWL (95%) group than URS (80%) and PCNL (81%) (P.001). The distribution of median income was significantly different amongst the 3 surgeries with higher income classes overutilizing SWL and underutilizing PCNL compared to lower income classes (P.001). In linear regression modeling, the proportion of SWL in a postal code was positively associated with median income (ROur study suggests that socioeconomic status impacts urolithiasis surgical management, underscoring disparity recognition importance in endourologic care and ensuring appropriate surgical care regardless of socioeconomic status.
- Published
- 2021
- Full Text
- View/download PDF
13. Sequential Chemotherapy with Gemcitabine and Docetaxel: Breaking the Chains of bacillus Calmette-Guérin
- Author
-
Joshua J. Meeks, Wade J. Sexton, and Peter E. Clark
- Subjects
Carcinoma, Transitional Cell ,Administration, Intravesical ,Adjuvants, Immunologic ,Urinary Bladder Neoplasms ,Urology ,BCG Vaccine ,Humans ,Docetaxel ,Deoxycytidine ,Mycobacterium bovis ,Gemcitabine - Published
- 2022
14. Clinical Utility of Postneoadjuvant Chemotherapy Computerized Tomography for Muscle Invasive Urothelial Bladder Cancer
- Author
-
James T. Kearns, William M. Worrilow, Stephen B. Riggs, Peter E. Clark, Jiaxian He, Kris E. Gaston, Caitlin Hensel, and Sagar R. Patel
- Subjects
Chemotherapy ,medicine.medical_specialty ,Bladder cancer ,business.industry ,Urology ,medicine.medical_treatment ,Muscle invasive ,medicine.disease ,Cystectomy ,Medicine ,Radiology ,Tomography ,business ,Neoadjuvant therapy - Abstract
Introduction:For muscle invasive bladder cancer, computerized tomography scans are often used before cystectomy to optimize surgical decision planning. The aim of this study is to evaluate ...
- Published
- 2021
- Full Text
- View/download PDF
15. A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry
- Author
-
Luc Multigner, William J. Blot, Alexander Lubwama, Stephen Watya, Peter E. Clark, Lucy Xia, Sara S. Strom, Adam S. Kibel, Jong Y. Park, Adam B. Murphy, Jennifer Cullen, Christopher A. Haiman, Florence Menegaux, Shiv Srivastava, Loreall Pooler, Mariana C. Stern, Anand P. Chokkalingam, Eric A. Klein, Wei Zheng, Thomas A. Sellers, Anselm Hennis, Dana C. Crawford, James L. Mohler, Jack A. Taylor, Esther M. John, Robin J. Leach, Sonja I. Berndt, Laurent Brureau, John D. Carpten, Susan Gundell, David V. Conti, Barbara Nemesure, Rosalind A. Eeles, Graham Casey, Pascal Blanchet, Benjamin A. Rybicki, Chad D. Huff, Maureen Sanderson, Stephen J. Chanock, Melinda C. Aldrich, Jay H. Fowke, Jennifer J. Hu, Diptasri Mandal, Sue A. Ingles, Kosj Yamoah, Kathleen A. Cooney, K. Govindasami, Ian M. Thompson, Patrick C. Walsh, Xin Sheng, Zsofia Kote-Jarai, Janet L. Stanford, Marie-Élise Parent, Christine Neslund-Dudas, Jianfeng Xu, William S. Bush, Phyllis J. Goodman, Meredith Yeager, Burcu F. Darst, Gary J. Smith, Victoria L. Stevens, Rick A. Kittles, Elaine A. Ostrander, Olivier Cussenot, Gyorgy Petrovics, Elizabeth T. H. Fontham, William B. Isaacs, Peggy Wan, Geraldine Cancel-Tassin, Susan M. Gapstur, Bettina F. Drake, Jeannette T. Bensen, University of Southern California (USC), Centre de Recherche pour les Pathologies Prostatiques. (CeRePP / UA 3104), CEREPP, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Pointe-à-Pitre/Abymes [Guadeloupe], U19 CA148537, U19 CA214253, R01 CA165862, and K99 CA246063, National Cancer Institute at the National Institutes of Health, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Urology ,Family history ,Population ,030232 urology & nephrology ,Black People ,Familial prostate cancer ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Familial clustering ,Risk Assessment ,Article ,Germline ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,Genetics ,Humans ,Medicine ,education ,Genetic variant ,Aged ,education.field_of_study ,business.industry ,Genetic Variation ,Prostatic Neoplasms ,8q24 ,Middle Aged ,medicine.disease ,Health equity ,3. Good health ,Disease Hotspot ,Germ Cells ,Prostate cancer screening ,African ancestry ,030220 oncology & carcinogenesis ,Health disparities ,business - Abstract
International audience; Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age
- Published
- 2020
- Full Text
- View/download PDF
16. Safety of decreasing ureteral stent duration following radical cystectomy
- Author
-
William Blair Townsend, Stephen B. Riggs, Peter E. Clark, Kris E. Gaston, Caitlin Hensel, William M. Worrilow, Hamza Beano, and Jiaxian He
- Subjects
Nephrology ,medicine.medical_specialty ,business.industry ,Urology ,medicine.medical_treatment ,Urinary diversion ,030232 urology & nephrology ,Stent ,Malignancy ,medicine.disease ,Logistic regression ,Surgery ,Cystectomy ,03 medical and health sciences ,0302 clinical medicine ,Increased risk ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,business ,Adverse effect - Abstract
We aim to assess the safety of decreasing ureteral stenting duration following Radical Cystectomy with Urinary Diversion (RCUD). We analyzed a prospectively and retrospectively collected dataset for cystectomy patients at our tertiary center. Adult patient who underwent RCUD for malignancy from January 2013 to February 2018 were included. Patients with a history of abdominal/pelvic radiation and continent diversions were excluded. The patient population was divided to late stent removal group (LSR-POD 14) and early stent removal group (ESR-POD5). Our endpoints were total stent duration, 90-day readmission, 90-day total-UTI, 90-day urinary-readmissions, complications and Ureteroenteric Stricture (UES) rates. Statistical methods included t test, Chi-squared test and multivariate logistic regression. One hundred and seventy-eight patients were included in the final analysis after inclusion/exclusion criteria were applied. The LSR (n = 74) and ESR (n = 104) groups were similar in preoperative characteristics except higher intracorporeal ileal conduit formation in ESR. The duration of stenting decreased significantly from approximately 15.5–5 days (P
- Published
- 2020
- Full Text
- View/download PDF
17. Limited Stage Small Cell Bladder Cancer: Outcomes of a Contemporary Cohort
- Author
-
Peter E. Clark, Derek Raghavan, Danielle Boselli, Claud Grigg, James T. Symanowski, Chad A. Livasy, Hamza Beano, Earle F. Burgess, Stephen B. Riggs, and Derek R. McHaffie
- Subjects
Limited Stage ,Oncology ,medicine.medical_specialty ,Bladder cancer ,business.industry ,Urology ,Cell ,030232 urology & nephrology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,business - Abstract
BACKGROUND: Limited stage small cell bladder cancer is curable with multi-modality therapy using external beam radiotherapy or radical cystectomy. The optimal management strategy for this rare disease is still debated, yet few case series have described patients treated after 2010. OBJECTIVE: To analyze outcomes from a contemporary cohort of patients undergoing definitive treatment. METHODS: Patients diagnosed with small cell bladder cancer after January 1, 2010 were identified from an institutional database. Clinical histories were collected by chart review. Survival outcomes were analyzed in patients who received curative-intent therapy consisting of bladder radiotherapy or cystectomy. RESULTS: Thirty patients with limited stage disease that received definitive therapy were identified. Seventeen patients received primary radiotherapy, and thirteen underwent cystectomy. Median age was 70 years. Median follow up was 39.6 months (range 7.2–95.8). The median overall survival of patients undergoing radiotherapy or cystectomy were 36.8 and 30.6 months, respectively (hazard ratio 0.99, 95% confidence interval 0.35–2.85). The median metastasis free survival for patients receiving radiotherapy was not reached, and 18.9 months in the cystectomy group (hazard ratio 0.94, 95% confidence interval 0.34–2.61). The most common sites of relapse were lymph node (n = 6) and bone (n = 5). Brain metastases were less common (n = 3). CONCLUSIONS: Patients receiving cystectomy or radiotherapy had similar outcomes in this contemporary series, but definitive comparisons are limited by the cohort size and high censoring rate (53%). Survival in our cohort is improved compared with older reports, though outcomes remain poor, reiterating the need for better therapeutic options.
- Published
- 2020
- Full Text
- View/download PDF
18. Safety and effectiveness of percutaneous renal cryoablation with conscious sedation
- Author
-
Holt Evans, Chris M. Teigland, Stephen B. Riggs, Kris E. Gaston, Ornob P Roy, Sagar R. Patel, Sean Francois, Peter E. Clark, and Tiagpaul Bhamber
- Subjects
animal structures ,Percutaneous ,Percutaneous renal cryoablation ,complications ,Urology ,medicine.medical_treatment ,Sedation ,030232 urology & nephrology ,urologic and male genital diseases ,Treatment failure ,disease recurrence ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,general anaesthesia ,General anaesthesia ,030219 obstetrics & reproductive medicine ,business.industry ,conscious sedation ,Cryoablation ,Oncology/ Reconstruction ,Under local anaesthesia ,Anesthesia ,medicine.symptom ,business ,Research Article - Abstract
Objective To investigate complications and treatment failure rates of percutaneous renal cryoablation (PRC) for small renal masses under local anaesthesia and conscious sedation (LACS), to assess the safety and effectiveness of this approach, as PRC is typically performed under general anaesthesia (GA). Patients and methods We retrospectively reviewed PRC under LACS from 2003 to 2017. We analysed perioperative parameters between patients who successfully underwent PRC under LACS and patients with post-procedural complications or treatment failure (renal mass enhancement after successful intraoperative tumour ablation). Two-sided non-parametric and Fisher’s exact tests were performed to compare uncomplicated or disease-free PRC with the complication or treatment failure group, respectively. Results A total of 100 PRCs under LACS were performed during the study period. Of these patients, six patients had at least one postoperative complication (6%), and treatment failure was diagnosed in nine patients (9%) after PRC [mean (SD) follow-up of 42.7 (26.6) months]. The procedural failure rate was 1%. No ablations were converted to GA. The mean tumour size was smaller in patients who had no complications during PRC compared to those who did, at a mean (SD) of 2.2 (0.6) cm vs 3.0 (1.0) cm (P = 0.039). The use of more intraoperative probes during the PRC was also associated with complications, at a mean (SD) 3.0 (1.4) vs 1.8 (0.8) (P = 0.021). Conclusions PRC under LACS is an effective and safe procedural approach for managing small renal masses with low complication, treatment failure, and procedural failure rates. Larger renal masses and intraoperative use of multiple probes is associated with an increased risk of PRC complications. Abbreviations BMI: body mass index; CCI: Charlson Comorbidity Index; GA: general anaesthesia; LACS: local anaesthesia and conscious sedation; PRC: percutaneous renal cryoablation; R.E.N.A.L.: Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location
- Published
- 2020
- Full Text
- View/download PDF
19. Geographic Variation of Infectious Complications Following Prostate Biopsy in The United States: Results From a Population-Based Cohort of Privately Insured Patients
- Author
-
Jeffrey C. Morrison, Anessa Sax-Bolder, Boris Gershman, Badrinath Konety, Peter E. Clark, Christopher M. Gonzalez, Michael R. Bronsert, Granville Lloyd, Rodrigo Rodrigues Pessoa, Eric Ballon-Landa, and Simon P. Kim
- Subjects
Male ,Cohort Studies ,Image-Guided Biopsy ,Insurance, Health ,Urology ,Biopsy ,Prostate ,Humans ,Prostatic Neoplasms ,Middle Aged ,United States - Abstract
To elucidate regional trends of infectious complications following transrectal ultrasound prostate biopsy (TRUS-PB) from a national, privately-insured database.Using Market Scan, we identified all men who underwent TRUS-PB from 2010 to 2015. Infectious complications (UTI, prostatitis, sepsis) occurring 30 days after the prostate biopsy from emergency room (ER) visits or hospital admissions constituted the primary outcomes. We analyzed unadjusted and adjusted rates of infectious complications from ER visits and hospital admissions per 100 prostate biopsies by state. Multivariable logistic regression analyses were used to identify patient covariates associated with infectious complications.During the study interval, we identified 193,490 patients who underwent TRUS-PB. The mean age was 57.6 years (SD: 5.0). Over time the unadjusted national rates of infectious complications remained similar from 0.4 ER visits per 100 prostate biopsies in 2010 -0.2 in 2015 (P = 0.83), and 1.2 hospital admissions per 100 prostate biopsies in 2010 to 1.1 in 2015 (P= 0.58). Connecticut had the lowest unadjusted infectious complication rate per 100 biopsies at 0.64, whereas West Virginia had the highest at 2.34. Multivariable analysis revealed higher Elixhauser status and patient age were associated with higher odds of infectious complications (P0.05).While rates of infectious complications attributable to prostate biopsies remain relatively stable, significant variation exists at the state level regarding this adverse outcome.
- Published
- 2022
20. Identification of potential biomarkers and novel therapeutic targets through genomic analysis of small cell bladder carcinoma and associated clinical outcomes
- Author
-
Earle F. Burgess, J. Alexa Sanders, Chad Livasy, James Symanowski, Zoran Gatalica, Nury M. Steuerwald, David Arguello, Cory R. Brouwer, W. Michael Korn, Claud M. Grigg, Jason Zhu, Justin T. Matulay, Peter E. Clark, Elisabeth I. Heath, and Derek Raghavan
- Subjects
Oncology ,Urinary Bladder Neoplasms ,Urology ,Carcinoma ,Mutation ,Urinary Bladder ,Biomarkers, Tumor ,Humans ,Genomics ,Neoplasm Recurrence, Local ,Prognosis ,Xeroderma Pigmentosum Group D Protein - Abstract
Small cell bladder carcinoma (SCBC) represents a rare histologic variant with a poor prognosis and for which no routine biomarkers exist. Limited reports of genomic sequencing in SCBC have demonstrated a high prevalence of TP53 and RB1 gene mutations, though the prognostic value of these and other gene variants in SCBC remains undefined. In this study, we performed targeted genomic sequencing on a cohort of SCBC patients and correlated genomic findings with clinical outcomes to identify potential novel biomarkers.Thirty-one patients with SCBC and available treatment-naïve tumor specimens were identified from an institutional database (23 limited stage [LS], 8 extensive stage [ES]). Small cell carcinoma specimens were microdissected and subjected to tumor next-generation whole-exon sequencing with a 592 gene panel. Kaplan-Meier techniques and Cox proportional hazards models were used to evaluate genomic aberration association with relapse-free survival (RFS) and overall survival (OS) in the limited stage cohort.The most common pathogenic gene variants included ARID1A (48%), TP53 (48%) and RB1 (48%). Mutations in genes with potential therapeutic targets not routinely evaluated in SCBC included BRCA1/2 (16%), POLE (13%), JAK2 (13%), PDGFB (13%) and FGFR3 (3%). Multiple novel biomarker candidates showed trends for improvements in OS in the LS subset including ERCC2 (HR 0.322, P = 0.122) and RB1 (HR 0.481, P = 0.182), while LS patients with TP53 mutations (HR 2.730, P = 0.056), and MCL1 gene amplification (HR 4.183, P = 0.018) suggested inferior OS. Additionally, gene or copy number variants with potential prognostic benefit included UBR5 and DAXX (P = 0.02, [hazard ratios nonestimable due to zero events in biomarker positive groups]).These results support the role for tumor genomic profiling in SCBC and identify multiple potential novel biomarkers and therapeutic targets in this rare disease. Efforts to validate these findings should lead to improved decision-making and treatment outcomes in SCBC.
- Published
- 2022
21. Reply by Authors
- Author
-
Miguel Rodriguez-Homs, Rodrigo Rodrigues Pessoa, Badrinath Konety, Boris Gershman, Peter E. Clark, Michael Bronsert, Thomas W. Flaig, Sarah E. Tevis, Granville Lloyd, Jeffrey C. Morrison, and Simon P. Kim
- Subjects
Urology - Published
- 2022
- Full Text
- View/download PDF
22. MP30-14 5-ARI USAGE ASSOCIATED WITH MORE ADVANCED PROSTATE CANCER AT DIAGNOSIS
- Author
-
Caroline Miller, Jason Zhu, Caroline Lu, Wei Sha, Emily Roebuck, Justin T. Matulay, James T. Kearns, Stephen B. Riggs, Peter E. Clark, Kris E. Gaston, Claud Grigg, and Earle F. Burgess
- Subjects
Oncology ,medicine.medical_specialty ,Prostate biopsy ,Referral ,medicine.diagnostic_test ,business.industry ,Urology ,medicine.disease ,Collaborative group ,Prostate cancer ,Internal medicine ,Medicine ,Prostate Cancer Prevention Trial ,business - Abstract
INTRODUCTION AND OBJECTIVE:Prostate cancer (PCa) risk is often modeled at referral based on Prostate Cancer Prevention Trial (PCPT) and Prostate Biopsy Collaborative Group (PBCG) risk calculators, ...
- Published
- 2021
- Full Text
- View/download PDF
23. MP34-10 SOCIAL DETERMINANTS OF HEALTH SCREENING PILOT IN TWO URBAN UROLOGY CLINICS
- Author
-
Stephen L Guice, Gillian Stearns, Ornob P Roy, Emily Roebuck, Brisa Urquieta de Hernandez, Stephen B. Riggs, Peter E. Clark, Manish N. Patel, and Mellisa Wheeler
- Subjects
medicine.medical_specialty ,business.industry ,Urology ,Family medicine ,Social needs ,medicine ,Social determinants of health ,business ,Health outcomes - Abstract
INTRODUCTION AND OBJECTIVE:Unmet social needs such as food or housing lead to adverse health outcomes and contribute to health inequities. Multiple validated social determinants of health (SDOH) sc...
- Published
- 2021
- Full Text
- View/download PDF
24. MP30-12 RACIAL AND SOCIOECONOMIC DISPARITIES IN MRI-FUSION BIOPSY UTILIZATION FOR THE DETECTION OF PROSTATE CANCER
- Author
-
James T. Kearns, Stephen B. Riggs, Earle F. Burgess, Caroline Lu, Kris E. Gaston, Emily Roebuck, Peter E. Clark, Jason Zhu, Claud Grigg, Caroline Miller, Justin T. Matulay, and Wei Sha
- Subjects
Oncology ,medicine.medical_specialty ,Prostate cancer ,business.industry ,Urology ,Internal medicine ,medicine ,medicine.disease ,business ,Socioeconomic status ,Fusion Biopsy - Abstract
INTRODUCTION AND OBJECTIVE:MRI-ultrasound fusion biopsies (MRI-Bx) have improved the detection of clinically significant prostate cancer. A recent study demonstrated racial disparities in MRI-Bx ut...
- Published
- 2021
- Full Text
- View/download PDF
25. MP49-07 EFFICACY AND SAFETY OF RENAL CRYOABLATION IN THE TREATMENT OF RENAL CELL CARCINOMA: A MULTI-CENTER PROSPECTIVE REGISTRY STUDY
- Author
-
Stephen J. Savage, Peter E. Clark, and S. Duke Herrell
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Urology ,medicine.medical_treatment ,Registry study ,Treatment options ,Cryoablation ,urologic and male genital diseases ,medicine.disease ,female genital diseases and pregnancy complications ,Renal cell carcinoma ,Internal medicine ,medicine ,business ,neoplasms - Abstract
INTRODUCTION AND OBJECTIVE:Management of small renal cell carcinoma (RCC), specifically clinical T1a RCC, includes a variety of treatment options. However, many of the studies supporting these opti...
- Published
- 2021
- Full Text
- View/download PDF
26. Perioperative Oral Nutrition Supplementation Reduces Prevalence of Sarcopenia following Radical Cystectomy: Results of a Prospective Randomized Controlled Trial
- Author
-
Joseph A. Smith, Kareem Fakhoury, Heidi J. Silver, Veronica Ralls, Chad R. Ritch, Sam S. Chang, Muang H. Thu, Michael S. Cookson, Peter E. Clark, and David F. Penson
- Subjects
medicine.medical_specialty ,business.industry ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Perioperative ,medicine.disease ,law.invention ,Nutrition supplementation ,Cystectomy ,03 medical and health sciences ,0302 clinical medicine ,Primary outcome ,Randomized controlled trial ,law ,Internal medicine ,Sarcopenia ,medicine ,Multivitamin ,Prospective cohort study ,business - Abstract
Purpose:We designed a prospective randomized, controlled pilot trial to investigate the effects of an enriched oral nutrition supplement on body composition and clinical outcomes following radical cystectomy.Materials and Methods:A total of 61 patients were randomized to an oral nutrition supplement or a multivitamin multimineral supplement twice daily during an 8-week perioperative period. Body composition was determined by analyzing abdominal computerized tomography images at the L3 vertebra. Sarcopenia was defined as a skeletal muscle index of less than 55 cm2/m2 in males and less than 39 cm2/m2 in females. The primary outcome was the difference in 30-day hospital free days. Secondary outcomes included hospital length of stay, complications, readmissions and mortality.Results:The oral nutrition supplement group lost less weight (–5 vs –6.5 kg, p = 0.04) compared to the multivitamin multimineral supplement group. The proportion of patients with sarcopenia did not change in the oral nutrition supplement ...
- Published
- 2019
- Full Text
- View/download PDF
27. Impact of dedicated renal enhanced recovery after surgery (RERAS) program on postoperative opioid consumption and evaluation of surgeon-specific compliance to the program
- Author
-
Emily H. Roebuck, Samuel J. Ivan, Myra M. Robinson, William M. Worrilow, Kris E. Gaston, Justin T. Matulay, Ornob P. Roy, Peter E. Clark, and Stephen B. Riggs
- Subjects
Analgesics, Opioid ,Male ,Surgeons ,Postoperative Complications ,Oncology ,Urology ,Humans ,Length of Stay ,Enhanced Recovery After Surgery ,Retrospective Studies - Abstract
Enhanced Recovery After Surgery (ERAS) protocols have been increasingly applied to urologic surgeries such as cystectomy and prostatectomy, though research defining protocols and outcomes for renal ERAS programs (RERAS) for nephrectomy remains limited. We aim to assess perioperative outcomes following implementation of our RERAS protocol modified from ERAS society cystectomy guidelines, as well as describe compliance with protocol guidelines.We performed a retrospective cohort analysis of 400 patients who underwent partial or radical nephrectomy between October 2017 and August 2020. RERAS protocol was initiated September 30, 2018, and patients were categorized into pre- and post-RERAS implementation cohorts based on surgery date. Perioperative outcomes including complications, 30-day readmissions, length of stay, and opioid consumption were compared across pre- and post-RERAS cohorts. Protocol compliance was reported based on adherence to program recommendations.Among 400 patients included in analysis, the pre-RERAS cohort included 133 patients and the post-RERAS cohort included 267 patients. There were no differences in overall complications (P = 0.354) and 30-day readmissions (P = 0.078). Length of stay (P0.001) and postoperative opioid consumption (P0.001) were significantly reduced post-RERAS. We observed an increase in compliance with RERAS recommendations over time (P0.001).RERAS implementation was associated with decreased length of stay and opioid usage, underscoring the benefits of program adoption in an era of opioid dependence and strained hospital capacity. Successful initiation of a RERAS protocol requires intentional organization and buy in from all providers involved.
- Published
- 2022
- Full Text
- View/download PDF
28. Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-up: AUA Guideline: Part II
- Author
-
Steven C. Campbell, Robert G. Uzzo, Jose A. Karam, Sam S. Chang, Peter E. Clark, and Lesley Souter
- Subjects
Urology ,Clinical Decision-Making ,Humans ,Continuity of Patient Care ,Watchful Waiting ,Risk Assessment ,Kidney Neoplasms - Abstract
This AUA Guideline focuses on active surveillance (AS) and follow-up after intervention for adult patients with clinically-localized renal masses suspicious for cancer, including solid enhancing tumors and Bosniak 3/4 complex cystic lesions.In January 2021, the Renal Mass and Localized Renal Cancer guideline underwent additional amendment based on a current literature-search. This literature search retrieved additional studies published between July 2016 to October 2020 using the same Key Questions and search criteria from the Renal Mass and Localized Renal Cancer guideline. When sufficient evidence existed, the body of evidence was assigned strength-rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).AS with potential delayed intervention should be considered for patients with solid, enhancing renal masses2cm or Bosniak 3-4 lesions that are predominantly-cystic. Shared decision-making about AS should consider risks of intervention/competing mortality versus the potential oncologic benefits of intervention. Recommendations for renal mass biopsy and considerations for periodic clinical/imaging-based surveillance are discussed. After intervention, risk-based surveillance protocols are defined incorporating clinical/laboratory evaluation and abdominal/chest imaging designed to detect local/systemic recurrences and possible treatment-related sequelae, such as progressive renal-insufficiency.AS is a potential management strategy for some patients with clinically-localized renal masses that requires careful risk-assessment, shared decision-making and periodic-reassessment. Follow-up after intervention is designed to identify local/systemic recurrences and potential treatment-related sequelae. A risk-based approach should be prioritized with selective use of laboratory/imaging resources.
- Published
- 2021
29. Racial Disparities in Prostate Specific Antigen Screening and Referral to Urology in a Large, Integrated Health Care System: A Retrospective Cohort Study
- Author
-
Hazel Tapp, Jason Zhu, Earle F. Burgess, Tara Eaton, Timothy Hetherington, William E. Anderson, Yhenneko J. Taylor, Caroline Lu, Claud Grigg, Peter E. Clark, James T. Kearns, Kris E. Gaston, David C. Slawson, Oluwaseun Adeyemi, and Stephen B. Riggs
- Subjects
Adult ,Male ,medicine.medical_specialty ,Referral ,Urology ,System a ,White People ,Cohort Studies ,Prostate cancer ,parasitic diseases ,Health care ,medicine ,Humans ,Healthcare Disparities ,Referral and Consultation ,Early Detection of Cancer ,Aged ,Retrospective Studies ,business.industry ,Delivery of Health Care, Integrated ,Health services research ,Retrospective cohort study ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,United States ,Black or African American ,Prostate-specific antigen ,Prostate cancer screening ,business - Abstract
Contemporary trends and racial disparities in prostate cancer screening and referral to urology for prostate cancer risk are not well characterized, despite consensus that Black men are at higher risk for poor prostate cancer outcomes. The objective of this study was to characterize current racial disparities in prostate cancer screening and referral from primary care to urology for prostate cancer concern within our large, integrated health care system.This retrospective cohort study used data from Atrium Health's enterprise data warehouse, which includes patient information from more than 900 care locations across North Carolina, South Carolina and Georgia. We included all men seen in the ambulatory or outpatient setting between 2014 and 2019 who were ≥40 years old. Clinical and demographic data were collected for all men, including age and race. Racial outcomes were reported for all groups with2% representation in the population. Between-group comparisons were determined using chi-squared analysis, Wilcoxon rank sum testing and multivariable logistic regression, with significance defined as p0.05.We observed a significant decrease in prostate specific antigen testing across all age and racial groups in a cohort of 606,985 men at Atrium Health, including 87,189 Black men, with an overall relative decline of 56%. As compared to White men, Black men were more likely to undergo prostate specific antigen testing (adjusted OR 1.24, 95% CI 1.22-1.26) and be referred to urology for prostate cancer (adjusted OR 1.94, 95% CI 1.75-2.16).There was a continued significant decline in prostate cancer screening between 2014 and 2019. Despite having modestly elevated odds of being screened for prostate cancer compared to White men, Black men are relatively underscreened when considering that those who undergo prostate specific antigen screening are more likely to be referred by primary care to urology for additional prostate cancer diagnostic evaluation.
- Published
- 2021
30. Epidemiology, prevention, screening, diagnosis, and evaluation: update of the ICUD-SIU joint consultation on bladder cancer
- Author
-
Rafael Sanchez-Salas, Ashish M. Kamat, H. Barton Grossman, Lambertus A. Kiemeney, Bernard Malavaud, Makarand Khochikar, Robert S. Svatek, Mark S. Soloway, Raghunandan Vikram, Peter E. Clark, Michael S. Cookson, Maurizio Brausi, Mario I. Fernández, and Alina Vrieling
- Subjects
medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Population Dynamics ,Population ,030232 urology & nephrology ,Disease ,Narrow Band Imaging ,03 medical and health sciences ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,Risk Factors ,Epidemiology ,Prevalence ,Tobacco Smoking ,medicine ,Humans ,Risk factor ,Intensive care medicine ,education ,Early Detection of Cancer ,Societies, Medical ,Neoplasm Staging ,Carcinoma, Transitional Cell ,education.field_of_study ,Bladder cancer ,business.industry ,Incidence ,Incidence (epidemiology) ,Cystoscopy ,Evidence-based medicine ,medicine.disease ,Magnetic Resonance Imaging ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Practice Guidelines as Topic ,Smoking cessation ,Smoking Cessation ,Tomography, X-Ray Computed ,business ,Algorithms - Abstract
To update current recommendations on prevention, screening, diagnosis, and evaluation of bladder cancer (BC) based on a thorough assessment of the most recent literature on these topics. A non-systematic review was performed, including articles until June 2017. A variety of original articles, reviews, and editorials were selected according to their epidemiologic, demographic, and clinical relevance. Assessment of the level of evidence and grade of recommendations was performed according to the International Consultation on Urological Diseases grading system. BC is the ninth most common cancer worldwide with 430,000 new cases in 2012. Currently, approximately 165,000 people die from the disease annually. Absolute incidence and prevalence of BC are expected to rise significantly during the next decades because of population ageing. Tobacco smoking is still the main risk factor, accounting for about 50% of cases. Smoking cessation is, therefore, the most relevant recommendation in terms of prevention, as the risk of developing BC drops almost 40% within 5 years of cessation. BC screening is not recommended for the general population. BC diagnosis remains mainly based on cystoscopy, but development of new endoscopic and imaging technologies may rapidly change the diagnosis algorithm. The same applies for local, regional, and distant staging modalities. A thorough understanding of epidemiology, risk factors, early detection strategies, diagnosis, and evaluation is essential for correct, evidence-based management of BC patients. Recent developments in endoscopic techniques and imaging raise the hope for providing better risk-adopted approaches and thereby improving clinical outcomes.
- Published
- 2019
31. PD40-05 CONTEMPORARY RACIAL DISPARITIES IN PSA SCREENING AND PROSTATE CANCER DIAGNOSIS IN A LARGE, INTEGRATED HEALTHCARE SYSTEM
- Author
-
James T. Kearns, Stephen B. Riggs, Caroline Lu, Jason Zhu, Oluwaseun Adeyemi, Peter E. Clark, Earle F. Burgess, William E. Anderson, Yhenneko J Taylor, Kris E. Gaston, and Timothy Hetherington
- Subjects
Oncology ,medicine.medical_specialty ,Prostate cancer ,Psa screening ,business.industry ,Urology ,Internal medicine ,medicine ,sense organs ,urologic and male genital diseases ,medicine.disease ,business ,Healthcare system - Abstract
INTRODUCTION AND OBJECTIVE:The USPSTF prostate cancer (PCa) screening guidelines have changed significantly in the past decade, from a recommendation against PSA-based screening in 2012 to a recomm...
- Published
- 2020
- Full Text
- View/download PDF
32. PD38-04 IMPACT OF USING THE PROSTATE BIOPSY COLLABORATE GROUP RISK CALCULATOR TO INFORM UROLOGY REFERRAL FOR PROSTATE CANCER RISK
- Author
-
Jason Zhu, James T. Kearns, Timothy Hetherington, Stephen B. Riggs, William R. Anderson, Peter E. Clark, Earle F. Burgess, and Kris E. Gaston
- Subjects
Prostate cancer risk ,medicine.medical_specialty ,Prostate biopsy ,Calculator ,medicine.diagnostic_test ,Referral ,law ,business.industry ,Urology ,General surgery ,medicine ,business ,law.invention - Published
- 2020
- Full Text
- View/download PDF
33. Reply by Authors
- Author
-
Emily Roebuck, Brisa Urquieta de Hernandez, Mellisa Wheeler, Gillian Stearns, Manish Patel, Stephen Guice, Ornob P Roy, Peter E Clark, and Stephen B Riggs
- Subjects
Urology - Published
- 2022
- Full Text
- View/download PDF
34. Renal Mass and Localized Renal Cancer: AUA Guideline
- Author
-
Jeffrey A. Cadeddu, Mohamad E. Allaf, Robert G. Uzzo, Brian J. Davis, Leo Giambarresi, Peter E. Clark, Steven C. Campbell, Eric B Bass, Bradley C. Leibovich, Brian R. Lane, Debra A. Gervais, Susie L. Hu, Anthony Chang, Philip M. Pierorazio, and Ithaar Derweesh
- Subjects
Ablation Techniques ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Renal function ,Nephrectomy ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Biopsy ,medicine ,Renal mass ,Humans ,Watchful Waiting ,Intensive care medicine ,medicine.diagnostic_test ,business.industry ,Patient Selection ,Cancer ,Guideline ,medicine.disease ,Kidney Neoplasms ,United States ,Surgery ,030220 oncology & carcinogenesis ,business ,Watchful waiting - Abstract
This AUA Guideline focuses on evaluation/counseling and management of adult patients with clinically localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.Systematic review utilized research from the Agency for Healthcare Research and Quality and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A/B/C (Strong/Moderate/Conditional Recommendations, respectively) with additional statements presented as Clinical Principles or Expert Opinions.Great progress has been made since the previous guidelines on management of localized renal masses were released (2009). The current guidelines provide updated, evidence-based recommendations regarding evaluation/counseling of patients with clinically localized renal masses, including the evolving role of renal mass biopsy. Given great variability of clinical, oncologic and functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Management options (partial nephrectomy/radical nephrectomy/thermal ablation/active surveillance) are reviewed including recent data about comparative effectiveness and potential morbidities. Oncologic issues are prioritized while recognizing that functional outcomes are of great importance for survivorship for most patients with localized kidney cancer. A more restricted role for radical nephrectomy is recommended following well-defined selection criteria. Priority for partial nephrectomy is recommended for clinical T1a lesions, along with selective use of thermal ablation, particularly for tumors ≤3.0 cm. Important considerations for shared decision-making about active surveillance are explicitly defined.Several factors should be considered during counseling/management of patients with clinically localized renal masses, including general health/comorbidities, oncologic potential of the mass, pertinent functional issues and relative efficacy/potential morbidities of various management strategies.
- Published
- 2017
- Full Text
- View/download PDF
35. TPX2 as a prognostic indicator and potential therapeutic target in clear cell renal cell carcinoma
- Author
-
Lan L. Gellert, Zachary A. Glaser, Peter E. Clark, David F. Penson, Harold D. Love, Stanley Duke Herrell, Daniel A. Barocas, Sam S. Chang, Shunhua Guo, and Michael S. Cookson
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pathology ,Urology ,medicine.medical_treatment ,Cell Cycle Proteins ,Kidney ,Disease-Free Survival ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,RNA, Messenger ,Carcinoma, Renal Cell ,Aged ,Aurora Kinase A ,Neoplasm Staging ,Aged, 80 and over ,Tissue microarray ,Genitourinary system ,business.industry ,Nuclear Proteins ,DNA Methylation ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,Nephrectomy ,Survival Rate ,Clear cell renal cell carcinoma ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,Immunohistochemistry ,Female ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business ,Microtubule-Associated Proteins ,Immunostaining ,Follow-Up Studies - Abstract
Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA).Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC. TPX2 expression by immunohistochemistry on TMA was assessed by a genitourinary pathologist. Clinical data were extracted and linked to TMA cores. TPX2 and Aurora-A mRNA coexpression were evaluated in the TCGA cohort. Overall survival (OS), cancer-specific survival, and recurrence-free survival (RFS) were analyzed using the Kaplan-Meier method and log-rank statistics. Univariate and multivariate analyses were conducted using Cox proportional hazard models.Median follow-up time for the TCGA cohort was 3.07 years. Aurora-A and TPX2 mRNA coexpression were significantly correlated (Pearson correlation = 0.918). High TPX2 mRNA expression was associated with advanced stage, metastasis, poor OS, and RFS. Median follow-up time for the TMA cohort was 5.3 years. Elevated TPX2 protein expression, defined as greater than 75th percentile staining intensity, was identified in 47/207 (22.7%) patients. Increased TPX2 immunostaining was associated with poor OS (P = 0.0327, 53% 5-year mortality), cancer-specific survival (P0.01, 47.8% 5-year cancer-specific mortality), RFS (P = 0.0313, 73.6%, 5-year recurrence rate), grade, T stage, and metastasis. Multivariate analysis demonstrated elevated expression served as an independent predictor of RFS (hazard ratio = 3.62 (1.13-11.55), P = 0.029).We show TPX2, a regulator of Aurora-A, is associated with high grade and stage of ccRCC, and is an independent predictor of recurrence. Future studies are warranted testing its role in ccRCC biology, and its potential as a therapeutic target.
- Published
- 2017
- Full Text
- View/download PDF
36. EDITORIAL COMMENT
- Author
-
Peter E, Clark
- Subjects
Urology - Published
- 2020
- Full Text
- View/download PDF
37. Implementation of a Dedicated Enhanced Recovery after Surgery (ERAS) Program for Radical Cystectomy Patients is Associated With Decreased Postoperative Inpatient Opioid Usage and Pain Scores
- Author
-
Hamza Beano, Stephen B. Riggs, Myra M. Robinson, William M. Worrilow, Blair Parker, Peter E. Clark, William Blair Townsend, and Kris E. Gaston
- Subjects
Male ,Visual analogue scale ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Cystectomy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Dosing ,Practice Patterns, Physicians' ,Enhanced recovery after surgery ,Aged ,Pain Measurement ,Retrospective Studies ,Pain, Postoperative ,business.industry ,Retrospective cohort study ,Middle Aged ,Analgesics, Opioid ,Hospitalization ,Opioid ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Pill ,Anesthesia ,Morphine ,Female ,business ,Enhanced Recovery After Surgery ,medicine.drug - Abstract
Objective To measure differences in post-operative opioid usage and pain scores between pre- and post-Enhanced Recovery after Surgery (ERAS) radical cystectomy (RC) patients in an effort to optimize outcomes. Study design We performed a retrospective cohort study from a single institution from January 1, 2015 to July 31, 2018 among 86 and 108 pre- and post-ERAS RC patients. The primary endpoints were total mean opioid usage (morphine equivalent daily dosing or MEDD) and mean pain scores (Visual Analog Scale) on postoperative days (POD) 1-3. Secondary endpoints were number of opioid pills prescribed at discharge and within 30 days of discharge. Multivariable model selection was carried out with forward selection and backward elimination to identify variables associated with key outcomes. Results Total mean usage of opioids and mean pain scores were significantly lower in post-ERAS vs pre-ERAS patients across POD 1-3, respectively (32.90 MEDD vs 99.86 MEDD, P ≤ .001; 3.51 vs 4.17, P = .003). The median number of opioid pills prescribed at discharge was significantly lower in the post-ERAS group compared to pre-ERAS (30 pills vs 45 pills, P = .046) as well as the median number opioid pills prescribed within 30 days of discharge (40 pills vs 50 pills, P = .001). Conclusion Our study suggests that a dedicated ERAS protocol following RC might be superior to traditional, non-ERAS methods in reducing postoperative opioid use and pain scores.
- Published
- 2019
38. Increased nuclear factor I/B expression in prostate cancer correlates with AR expression
- Author
-
Sarah E. Kohrt, Wisam N. Awadallah, Petra Popovics, Jagpreet S. Nanda, Justin M M Cates, Magdalena M. Grabowska, Giovanna A. Giannico, Janni Mirosevich, and Peter E. Clark
- Subjects
Male ,0301 basic medicine ,Biochemical recurrence ,Urology ,Gene Expression ,Neuroendocrine differentiation ,Article ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Prostate ,Cell Line, Tumor ,medicine ,Humans ,030304 developmental biology ,0303 health sciences ,Tissue microarray ,biology ,business.industry ,Prostatic Neoplasms ,medicine.disease ,Immunohistochemistry ,3. Good health ,Androgen receptor ,NFI Transcription Factors ,Prostatic Neoplasms, Castration-Resistant ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,NFIB ,Receptors, Androgen ,Tissue Array Analysis ,030220 oncology & carcinogenesis ,Cancer research ,Synaptophysin ,biology.protein ,Transcriptome ,business - Abstract
BackgroundMost prostate cancers express androgen receptor (AR), and our previous studies have focused on identifying transcription factors that modify AR function. We have shown that nuclear factor I/B (NFIB) regulates AR activity in androgen-dependent prostate cancer cellsin vitro. However, the status of NFIB in prostate cancer was unknown.MethodsWe immunostained a tissue microarray including normal, hyperplastic, prostatic intraepithelial neoplasia, primary prostatic adenocarcinoma, and castration-resistant prostate cancer tissue samples for NFIB, AR, and synaptophysin, a marker of neuroendocrine differentiation. We interrogated publically available data sets in cBioPortal to correlateNFIBexpression and AR and neuroendocrine prostate cancer (NEPCa) activity scores. We analyzed prostate cancer cell lines for NFIB expression via Western blotting and used nuclear and cytoplasmic fractionation to assess where NFIB is localized. We performed coimmunoprecipitation studies to determine if NFIB and AR interact.ResultsNFIB increased in the nucleus and cytoplasm of prostate cancer samples versus matched normal controls, independent of Gleason score. Similarly, cytoplasmic AR and synaptophysin increased in primary prostate cancer. We observed strong NFIB staining in primary small cell prostate cancer. The ratio of cytoplasmic-to-nuclear NFIB staining was predictive of earlier biochemical recurrence in prostate cancer, once adjusted for tumor margin status. Cytoplasmic AR was an independent predictor of biochemical recurrence. There was no statistically significant difference between NFIB and synaptophysin expression in primary and castration-resistant prostate cancer, but cytoplasmic AR expression was increased in castrationresistant samples. In primary prostate cancer, nuclear NFIB expression correlated with cytoplasmic NFIB and nuclear AR, while cytoplasmic NFIB correlated with synaptophysin, and nuclear and cytoplasmic AR. In castration-resistant prostate cancer samples,NFIBexpression correlated positively with an AR activity score, and negatively with the NEPCa score. In prostate cancer cell lines, NFIB exists in several isoforms. We observed NFIB predominantly in the nuclear fraction of prostate cancer cells with increased cytoplasmic expression seen in castration-resistant cell lines. We observed an interaction between AR and NFIB through coimmunoprecipitation experiments.ConclusionWe have described the expression pattern of NFIB in primary and castrationresistant prostate cancer and its positive correlation with AR. We have also demonstrated AR interacts with NFIB.
- Published
- 2019
- Full Text
- View/download PDF
39. High aurora kinase expression identifies patients with muscle-invasive bladder cancer who have poor survival after neoadjuvant chemotherapy
- Author
-
Sally Trufan, Renato Guerreri, Caroline Naso, Earle F. Burgess, Chad A. Livasy, Aaron Hartman, James T. Symanowski, Claud Grigg, Derek Raghavan, and Peter E. Clark
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Urinary Bladder ,030232 urology & nephrology ,Kaplan-Meier Estimate ,Cystectomy ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Aurora kinase ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Medicine ,Aurora Kinase B ,Humans ,Aged ,Aurora Kinase A ,Cisplatin ,Aged, 80 and over ,Chemotherapy ,Bladder cancer ,business.industry ,Proportional hazards model ,Middle Aged ,medicine.disease ,Prognosis ,Neoadjuvant Therapy ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,Neoplasm Recurrence, Local ,business ,medicine.drug ,Follow-Up Studies - Abstract
Overexpression of aurora kinase A (AURKA) confers a poor prognosis in patients with urothelial carcinoma of the bladder. The prognostic value of high aurora kinase B (AURKB) expression in local bladder cancer is not well defined, and whether the prognostic value of either AURKA or AURKB is affected by the use of chemotherapy is unknown. We sought to characterize the impact of high AURKA and AURKB expression on clinical outcome in patients with muscle-invasive bladder cancer (MIBC) who received neoadjuvant chemotherapy (NAC).Immunohistochemistry for AURKA and AURKB was performed on pretreatment diagnostic transurethral resection of bladder tumor (TURBT) and matched cystectomy specimens in 50 subjects with MIBC who received NAC. Receiver operator characteristic curves (ROC) were calculated to assess the impact of AURKA and AURKB expression on pathologic response rate. Kaplan-Meier techniques and Cox proportional hazards models were used to assess the association with relapse-free survival (RFS) and overall survival (OS).Twenty-two of 50 [44%] patients had residual muscle-invasive (ypT2-4) urothelial carcinoma after NAC. Neither baseline tumor expression of AURKA (ROC = 0.57, P = 0.46) nor AURKB (ROC = 0.56, P = 0.87) predicted for ypT2-4 status. However, baseline expression of AURKA above the 75th percentile for this cohort was associated with an inferior RFS, (HR = 3.88, P = 0.008) and OS, (HR = 6.10, P0.001). Similar trends for worse survival outcomes were also observed for high AURKB levels (RFS, [HR = 2.2, P = 0.13] and OS, (HR = 2.25, P = 0.09).High baseline tumor AURKA and AURKB expression identified MIBC patients with inferior RFS and OS despite the use of NAC and may identify patients who should be prioritized for clinical trial enrollment rather than standard cisplatin-based chemotherapy.
- Published
- 2019
40. Diagnostic renal mass biopsy is associated with individual categories of PADUA and RENAL nephrometry scores: Analysis of diagnostic and concordance rates with surgical resection
- Author
-
Melissa M. Straub Hogan, Sandeep Arora, Justin M M Cates, Frances Cate, Woodson W. Smelser, Giovanna A. Giannico, Ricardo B. Fonseca, Jennifer B. Gordetsky, Meghan E. Kapp, Peter E. Clark, and Alice Coogan
- Subjects
Male ,Subset Analysis ,Surgical resection ,medicine.medical_specialty ,Urology ,Concordance ,Biopsy, Fine-Needle ,030232 urology & nephrology ,Kidney ,Article ,03 medical and health sciences ,0302 clinical medicine ,Biopsy ,Renal mass ,Humans ,Medicine ,skin and connective tissue diseases ,Renal sinus ,neoplasms ,Aged ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,Middle Aged ,Kidney Neoplasms ,body regions ,surgical procedures, operative ,Fine-needle aspiration ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Female ,Biopsy, Large-Core Needle ,Radiology ,business - Abstract
Background Renal mass biopsy (RMB) is a safe and accurate method for diagnosis and clinical management of renal masses. However, the non-diagnostic rate is a limiting factor. We tested the hypothesis that imaging characteristics and anatomic complexity of the mass may impact RMB diagnostic outcome using the preoperative aspects and dimensions used for an anatomical (PADUA) classification and radius-exophytic/endophytic-nearness-anterior/posterior-location (RENAL) score. Material and methods Single institution, retrospective study of 490 renal masses from 443 patients collected from 2001 to 2018. Outcome measurements include (1) diagnostic and concordance rates amongst RMB types and RMB with surgical resection specimens; (2) association between diagnostic RMB and anatomical complexity of renal masses. The analysis was conducted in unselected masses and small renal masses (SRMs). Results RMB was performed by fine needle aspiration (FNA), core needle biopsy (CNB), or both (FNA+CNB). Non-diagnostic rate was significantly higher for FNA compared to CNB and FNA+CNB in both unselected and SRMs. Subset analysis in the FNA+CNB group showed similar diagnostic rates for FNA and CNB. In unselected masses, specificity for FNA, CNB, and FNA+CNB was 100%. Sensitivity was higher for CNB (90.1%, P = 0.002) and FNA+CNB (96.3%, P = 0.004) compared to FNA (66.7%). For unselected masses, endophytic growth predicted a non-diagnostic CNB. R.E.N.A.L location entirely between the polar lines (central) and entirely above the upper polar line predicted a diagnostic CNB. Sonography-guidance predicted a diagnostic FNA. For SRMs, non-diagnostic CNB was associated with endophytic growth, while diagnostic CNB was associated with renal sinus invasion and operator experience. More cystic masses were sampled by FNA, but diagnostic results were similar for FNA and CNB. Conclusions Endophytic growth consistently predicted a non-diagnostic CNB in unselected and SRMs, whereas sonography-guidance predicted a diagnostic FNA. Cystic masses could be adequately sampled by FNA.
- Published
- 2021
- Full Text
- View/download PDF
41. Impact of 5-ALPHA reductase inhibitor use on prostate cancer risk at the time of urology referral
- Author
-
Timothy Hetherington, Jason Zhu, Earle F. Burgess, William E. Anderson, James T. Kearns, Peter E. Clark, Stephen B. Riggs, Kris E. Gaston, Justin T. Matulay, and Claud Grigg
- Subjects
Prostate cancer risk ,Cancer Research ,medicine.medical_specialty ,Referral ,business.industry ,Urology ,Hyperplasia ,Reductase ,urologic and male genital diseases ,medicine.disease ,respiratory tract diseases ,03 medical and health sciences ,5 Alpha-Reductase Inhibitor ,0302 clinical medicine ,Oncology ,Lower urinary tract symptoms ,030220 oncology & carcinogenesis ,Medicine ,business ,030215 immunology - Abstract
226 Background: 5-alpha reductase inhibitors (5-ARIs) are commonly used medications for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. One of the consequences of 5-ARI use is a 50% drop in serum PSA without a concomitant reduction in prostate cancer (PCa) risk. Previous work has suggested that 5-ARI use is associated with worse PCa-specific outcomes. The objective of this study was to evaluate the impact of 5-ARI use on patients’ PCa risk at the time of referral from primary care to urology. Methods: This retrospective cohort study included all men ≥ 40 years who had a PSA resulted between 2018-2019 and were seen in an ambulatory setting. PSA testing was determined through laboratory data in the electronic health record (EHR). Clinical and demographic data were collected for all men. 5-ARI use was determined through orders in the EHR. Men were assigned PCa risk according to both the Prostate Biopsy Collaborative Group (PBCG) and Prostate Cancer Prevention Trial (PCPT) risk calculators. PSA values were doubled for 5-ARI users prior to calculating risk. Referral to urology for PCa risk was determined using the narrative reason for referral associated with the referral order. Results: Between 2018-2019, 91,368 men had a PSA test, including 2,939 5-ARI users, and 88,429 non-users. Uncorrected median PSA and the proportion of men referred to urology for PCa risk were similar between the two groups (p = 0.60 and p = 0.17, respectively). Of men referred to urology for PCa risk, 5-ARI users had similar uncorrected PSA to non-users (p=0.86) but higher risk for high grade PCa once PSA correction was performed, median (IQR) 48% (24%) vs 28% (18%) using the PBCG and 21% (17%) vs 10% (10%) using the PCPT (p < 0.01 for both) (Table). Conclusions: Men taking 5-ARIs have significantly higher risk for high-grade PCa at time of referral to urology than non-users in this cohort. As the unadjusted PSA at referral to urology for PCa risk was the same between 5-ARI users and non-users, this indicates that the effect of 5-ARI use on serum PSA levels is not routinely accounted for when assessing PCa risk. Further study on interventions to account for 5-ARI use when screening for PCa are warranted. [Table: see text]
- Published
- 2021
- Full Text
- View/download PDF
42. NF-κB and androgen receptor variant 7 induce expression of SRD5A isoforms and confer 5ARI resistance
- Author
-
Robert J. Matusik, Peter E. Clark, David C. Austin, Omar Hameed, Ren J. Jin, Nicole L. Miller, Simon W. Hayward, Douglas W. Strand, Magdalena M. Grabowska, Harold L. Love, and Omar E. Franco
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Urology ,Biology ,medicine.disease ,Androgen receptor ,03 medical and health sciences ,5 Alpha-Reductase Inhibitor ,Prostate cancer ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,medicine.anatomical_structure ,Oncology ,Prostate ,Lower urinary tract symptoms ,030220 oncology & carcinogenesis ,Dihydrotestosterone ,SRD5A2 ,Internal medicine ,medicine ,Testosterone ,medicine.drug - Abstract
BACKGROUND Benign prostatic hyperplasia (BPH) is treated with 5α-reductase inhibitors (5ARI). These drugs inhibit the conversion of testosterone to dihydrotestosterone resulting in apoptosis and prostate shrinkage. Most patients initially respond to 5ARIs; however, failure is common especially in inflamed prostates, and often results in surgery. This communication examines a link between activation of NF-κB and increased expression of SRD5A2 as a potential mechanism by which patients fail 5ARI therapy. METHODS Tissue was collected from “Surgical” patients, treated specifically for lower urinary tract symptoms secondary to advanced BPH; and, cancer free transition zone from “Incidental” patients treated for low grade, localized peripheral zone prostate cancer. Clinical, molecular and histopathological profiles were analyzed. Human prostatic stromal and epithelial cell lines were genetically modified to regulate NF-κB activity, androgen receptor (AR) full length (AR-FL), and AR variant 7 (AR-V7) expression. RESULTS SRD5A2 is upregulated in advanced BPH. SRD5A2 was significantly associated with prostate volume determined by Transrectal Ultrasound (TRUS), and with more severe lower urinary tract symptoms (LUTS) determined by American Urological Association Symptom Score (AUASS). Synthesis of androgens was seen in cells in which NF-κB was activated. AR-FL and AR-V7 expression increased SRD5A2 expression while forced activation of NF-κB increased all three SRD5A isoforms. Knockdown of SRD5A2 in the epithelial cells resulted in significant reduction in proliferation, AR target gene expression, and response to testosterone (T). In tissue recombinants, canonical NF-κB activation in prostatic epithelium elevated all three SRD5A isoforms and resulted in in vivo growth under castrated conditions. CONCLUSION Increased BPH severity in patients correlates with SRD5A2 expression. We demonstrate that NF-κB and AR-V7 upregulate SRD5A expression providing a mechanism to explain failure of 5ARI therapy in BPH patients. Prostate 9999: XX–XX, 2016. © 2016 Wiley Periodicals, Inc.
- Published
- 2016
- Full Text
- View/download PDF
43. Use of venous-thrombotic-embolic prophylaxis in patients undergoing surgery for renal tumors: a questionnaire survey in the Nordic countries (The NORENCA -2 study)
- Author
-
Eirikur Gudmundsson, Frode Nilsen, Harry Nisen, Petrus Järvinen, Pernilla Sundqvist, Peter E. Clark, Bjarne Kromann-Andersen, Lars Lund, Christian Beisland, Magnus Fovaeus, Börje Ljungberg, Urologian yksikkö, Clinicum, Department of Surgery, and HUS Abdominal Center
- Subjects
medicine.medical_specialty ,thrombosis prophylaxis ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,minimally invasive methods ,complication ,venous-thrombotic-embolic prophylaxis kidney cancer ,GUIDELINES ,Nephrectomy ,Venous-thrombotic-embolic prophylaxis kidney cancer ,surgery ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,nephrectomy ,In patient ,Mortality ,THROMBOEMBOLISM PROPHYLAXIS ,Original Research ,030219 obstetrics & reproductive medicine ,business.industry ,Research and Reports in Urology ,Cancer ,Questionnaire ,Thromboembolism Prophylaxis ,Thrombosis prophylaxis ,3126 Surgery, anesthesiology, intensive care, radiology ,medicine.disease ,UROLOGICAL SURGERY ,mortality ,CANCER-SURGERY ,3. Good health ,UPDATE ,Minimally invasive methods ,Surgery ,business ,Complication ,Venous thromboembolism ,Prophylactic treatment - Abstract
Lars Lund,1,2 Harry Nisen,3 Petrus Järvinen,3 Magnus Fovaeus,4 Eirikur Gudmundsson,5 Bjarne Kromann-Andersen,6 Börje Ljungberg,7 Frode Nilsen,8 Pernilla Sundqvist,9 Peter E Clark,10 Christian Beisland11,12 1Department of Urology, Odense University Hospital, 2Clinical Institute, Southern University of Denmark, Odense, Denmark; 3Department of Urology, Helsinki University Hospital, Helsinki, Finland; 4Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Department of Urology, Landspitali University Hospital, Reykjavik, Iceland; 6Department of Urology, Herlev University Hospital, Copenhagen, Denmark; 7Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden; 8Department of Urology, Akershus University Hospital, Lörenskog, Norway; 9Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 10Department of Urology, Atrium Health, Charlotte, NC, USA; 11Department of Urology, Haukeland University Hospital, 12Department of Clinical Medicine, University of Bergen, Bergen, Norway Purpose: To examine the variation in venous thromboembolism prophylactic treatment (VTEP) among renal cancer patients undergoing surgery.Materials and methods: An Internet-based questionnaire on renal tumor management before and after surgery was mailed to all Nordic departments of urology. The questions focused on the use of VTEP and were subdivided into different surgical modalities.Results: Questionnaires were mailed to 91 institutions (response rate 53%). None of the centers used VTEP before surgery, unless the patient had a vena caval tumor thrombus. Overall, the VTEP utilized during hospitalization for patients undergoing renal surgery included early mobilization (45%), compression stockings (52%) and low-molecular-weight heparin (89%). In patients undergoing open radical Nx, 80% of institutions used VTEP during their hospitalization (23% compression stockings and 94% low-molecular-weight heparin). After leaving the hospital, the proportion and type of VTEP received varied considerably across institutions. The most common interval, used in 60% of the institutions, was for a period of 4 weeks. The restriction to the Nordic countries was a limitation and, therefore, may not reflect the practice patterns elsewhere. It is a survey study and, therefore, cannot measure the behaviors of those institutions that did not participate.Conclusion: We found variation in the type and duration of VTEP use for each type of local intervention for renal cancer. These widely disparate variations in care strongly argue for the establishment of national and international guidelines regarding VTEP in renal surgery. Keywords: venous-thrombotic-embolic prophylaxis kidney cancer, surgery, nephrectomy, mortality, complication, minimally invasive methods, thrombosis prophylaxis
- Published
- 2018
- Full Text
- View/download PDF
44. Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma
- Author
-
Kathryn M. Wilson, Sharon A. Savage, I-Min Lee, Stella Koutros, Gabriella Andreotti, Rosamonde E. Banks, Simone Benhamou, David Petillo, Laurie Burdette, Douglas F. Easton, Susanna C. Larsson, Peter Kraft, Marc Henrion, Lenka Foretova, Peng Li, H. Bas Bueno-de-Mesquita, Amanda Black, Konstantin G. Skryabin, Börje Ljungberg, Toni K. Choueiri, Loren Lipworth, Stephen J. Chanock, Robert Carreras-Torres, Sabrina L. Noyes, Olivier Cussenot, Marie Navratilova, Matthew L. Freedman, Mark Pomerantz, Wong-Ho Chow, David Zaridze, Eunyoung Cho, Lee E. Moore, James McKay, Lars J. Vatten, Ghislaine Scelo, Christopher G. Wood, Anush Mukeriya, Mirjana Mijuskovic, Jonathan N. Hofmann, Kevin M. Brown, Ulrike Peters, Valerie Gaborieau, Mark P. Purdue, Fiona Bruinsma, Richard J. Kahnoski, Paul Brennan, Susan J. Jordan, V. Janout, Cezary Cybulski, Timothy Eisen, Paul D.P. Pharoah, Howard S. Sesso, Hallie Carol, Neonila Szeszenia-Dabrowska, Garnet L. Anderson, Gianluca Severi, Céline Besse, Egor Prokhortchouk, Eric J. Duell, Satu Männistö, Geraldine Cancel-Tassin, Mitchell J. Machiela, Meredith Yeager, Eleonora Fabianova, Laura E. Beane Freeman, Mark A. Preston, Kvetoslava Koppova, John Anema, Jean-François Deleuze, G. Mark Lathrop, Victoria L. Stevens, Emily White, Zhaoming Wang, Stephanie J. Weinstein, Juhua Luo, Julie E. Buring, Viorel Jinga, Joshua N. Sampson, Peter Rudnai, Raviprakash T. Sitaram, Brian R. Lane, Stefan Rascu, Lisa Johnson, Jan Lubinski, Demetrius Albanes, Kristian Hveem, Leandro M. Colli, Dana Mates, Peter Selby, Miodrag Ognjanovic, Todd E. Edwards, Nathaniel Rothman, Richard S. Houlston, Matthieu Foll, Xifeng Wu, Peter E. Clark, Jolanta Lissowska, Vladimir Bencko, Ivana Holcatova, Anne Boland, James Larkin, Bin Tean Teh, J. Michael Gaziano, Hélène Blanché, Alicja Wolk, Neal D. Freedman, Federico Canzian, Mattias Johansson, Susan M. Gapstur, Yuanqing Ye, Tony Fletcher, Wen-Yi Huang, Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Eisen, Tim [0000-0001-9663-4873], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Risk ,Genetic variants ,Urology ,Genome-wide association study ,macromolecular substances ,urologic and male genital diseases ,Polymorphism, Single Nucleotide ,Risk Assessment ,Article ,03 medical and health sciences ,0302 clinical medicine ,Telomere Homeostasis ,Renal cell carcinoma ,Risk Factors ,Mendelian randomization ,Carcinoma ,Leukocytes ,Odds Ratio ,Medicine ,Humans ,Genetic Predisposition to Disease ,Carcinoma, Renal Cell ,Genetics ,Telomere length ,business.industry ,Case-control study ,Odds ratio ,Mendelian Randomization Analysis ,Telomere ,medicine.disease ,female genital diseases and pregnancy complications ,Kidney Neoplasms ,030104 developmental biology ,Phenotype ,030220 oncology & carcinogenesis ,Case-Control Studies ,Cancer research ,business ,Genome-Wide Association Study - Abstract
BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p
- Published
- 2018
- Full Text
- View/download PDF
45. Corrigendum re 'Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma' [Eur Urol 2017;72:747-54]
- Author
-
Jolanta Lissowska, Douglas F. Easton, Ivana Holcatova, Matthieu Foll, Mark Pomerantz, Susan M. Gapstur, Peter E. Clark, Mitchell J. Machiela, Amanda Black, G. Mark Lathrop, Miodrag Ognjanovic, Marie Navratilova, Bin Tean Teh, Yuanqing Ye, Tony Fletcher, Matthew L. Freedman, Zhaoming Wang, Alicja Wolk, Wen-Yi Huang, Timothy Eisen, Dana Mates, Mark A. Preston, Eric J. Duell, I-Min Lee, Anush Mukeriya, Fiona Bruinsma, James McKay, Jan Lubinski, Kathryn M. Wilson, Sharon A. Savage, Neal D. Freedman, Julie E. Buring, Raviprakash T. Sitaram, Hallie Carol, Rosamonde E. Banks, Victoria L. Stevens, Garnet L. Anderson, Joshua N. Sampson, Simone Benhamou, Céline Besse, Stefan Rascu, Mark P. Purdue, Konstantin G. Skryabin, Börje Ljungberg, Kristian Hveem, Federico Canzian, Marc Henrion, Richard S. Houlston, Xifeng Wu, Wong-Ho Chow, Neonila Szeszenia-Dabrowska, Jonathan N. Hofmann, Anne Boland, Peter Rudnai, Eunyoung Cho, Egor Prokhortchouk, Stella Koutros, Lee E. Moore, Cezary Cybulski, Mirjana Mijuskovic, Valerie Gaborieau, Paul D.P. Pharoah, Susan J. Jordan, Vladimir Janout, Susanna C. Larsson, Viorel Jinga, Stephen J. Chanock, Loren Lipworth, Kevin M. Brown, Olivier Cussenot, Sabrina L. Noyes, Brian R. Lane, Laurie Burdette, Ulrike Peters, Satu Männistö, Meredith Yeager, Mattias Johansson, James Larkin, Stephanie J. Weinstein, Juhua Luo, Demetrius Albanes, Robert Carreras-Torres, J. Michael Gaziano, H. B. Bueno-De-Mesquita, Christopher G. Wood, Lisa Johnson, David Petillo, Howard S. Sesso, Hélène Blanché, Vladimir Bencko, Peng Li, Ghislaine Scelo, Geraldine Cancel-Tassin, Lars J. Vatten, Jean-François Deleuze, Peter Selby, John Anema, Emily White, Lenka Foretova, Kvetoslava Koppova, David Zaridze, Gianluca Severi, Gabriella Andreotti, Paul Brennan, Leandro M. Colli, Todd E. Edwards, Eleonora Fabianova, Laura E. Beane Freeman, Richard J. Kahnoski, Nathaniel Rothman, Peter Kraft, and Toni K. Choueiri
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Urology ,Genetic variants ,MEDLINE ,medicine.disease ,Article ,Telomere ,03 medical and health sciences ,0302 clinical medicine ,Increased risk ,Renal cell carcinoma ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030212 general & internal medicine ,business - Abstract
It has come to our attention that authors Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, and Cezary Cybulski were not assigned to the correct affiliations. Their correct affiliations are as in the list above. Conflicts of interest: The authors have nothing to disclose.
- Published
- 2018
46. NF-κB and androgen receptor variant expression correlate with human BPH progression
- Author
-
Omar E. Franco, Nicole L. Miller, Ren J. Jin, Alex Jang, Simon W. Hayward, David C. Austin, Magdalena M. Grabowska, Peter E. Clark, Jay H. Fowke, Douglas W. Strand, Harold L. Love, Omar Hameed, and Robert J. Matusik
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Stromal cell ,business.industry ,Urology ,Inflammation ,Hyperplasia ,medicine.disease ,Androgen receptor ,03 medical and health sciences ,Prostate cancer ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Endocrinology ,Oncology ,Downregulation and upregulation ,Prostate ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,medicine.symptom ,Signal transduction ,business - Abstract
BACKGROUND Benign prostatic hyperplasia (BPH) is a common, chronic progressive disease. Inflammation is associated with prostatic enlargement and resistance to 5α-reductase inhibitor (5ARI) therapy. Activation of the nuclear factor-kappa B (NF-κB) pathway is linked to both inflammation and ligand-independent prostate cancer progression. METHODS NF-κB activation and androgen receptor variant (AR-V) expression were quantified in transition zone tissue samples from patients with a wide range of AUASS from incidental BPH in patients treated for low grade, localized peripheral zone prostate cancer to advanced disease requiring surgical intervention. To further investigate these pathways, human prostatic stromal and epithelial cell lines were transduced with constitutively active or kinase dead forms of IKK2 to regulate canonical NF-κB activity. The effects on AR full length (AR-FL) and androgen-independent AR-V expression as well as cellular growth and differentiation were assessed. RESULTS Canonical NF-κB signaling was found to be upregulated in late versus early stage BPH, and to be strongly associated with non-insulin dependent diabetes mellitus. Elevated expression of AR-variant 7 (AR-V7), but not other AR variants, was found in advanced BPH samples. Expression of AR-V7 significantly correlated with the patient AUASS and TRUS volume. Forced activation of canonical NF-κB in human prostatic epithelial and stromal cells resulted in elevated expression of both AR-FL and AR-V7, with concomitant ligand-independent activation of AR reporters. Activation of NF-κB and over expression of AR-V7 in human prostatic epithelial cells maintained cell viability in the face of 5ARI treatment. CONCLUSION Activation of NF-κB and AR-V7 in the prostate is associated with increased disease severity. AR-V7 expression is inducible in human prostate cells by forced activation of NF-κB resulting in resistance to 5ARI treatment, suggesting a potential mechanism by which patients may become resistant to 5ARI therapy. Prostate 76:491–511, 2016. © 2015 Wiley Periodicals, Inc.
- Published
- 2015
- Full Text
- View/download PDF
47. A Murine Model of K-RAS and β-Catenin Induced Renal Tumors Expresses High Levels of E2F1 and Resembles Human Wilms Tumor
- Author
-
Harold L. Moses, Harold N. Lovvorn, Austin Hembd, Harold D. Love, Peter E. Clark, Dina Polosukhina, Yajun Yi, Michael W. Pickup, and Roy Zent
- Subjects
Transcriptional Activation ,Genotype ,Urology ,Kidney development ,Biology ,Kidney ,Wilms Tumor ,Article ,Renal neoplasm ,Proto-Oncogene Proteins p21(ras) ,Mice ,medicine ,Animals ,beta Catenin ,Oligonucleotide Array Sequence Analysis ,Tissue microarray ,Oncogene ,Wnt signaling pathway ,Wilms' tumor ,medicine.disease ,Kidney Neoplasms ,Mice, Mutant Strains ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,medicine.anatomical_structure ,Catenin ,Cancer research ,Tumor Suppressor Protein p53 ,Transcriptome ,E2F1 Transcription Factor - Abstract
Wilms tumor is the most common renal neoplasm of childhood. We previously found that restricted activation of the WNT/β-catenin pathway in renal epithelium late in kidney development is sufficient to induce small primitive neoplasms with features of epithelial Wilms tumor. Metastatic disease progression required simultaneous addition of an activating mutation of the oncogene K-RAS. We sought to define the molecular pathways activated in this process and their relationship to human renal malignancies.Affymetrix® expression microarray data from murine kidneys with activation of K-ras and/or Ctnnb1 (β-catenin) restricted to renal epithelium were analyzed and compared to publicly available expression data on normal and neoplastic human renal tissue. Target genes were verified by immunoblot and immunohistochemistry.Mouse kidney tumors with activation of K-ras and Ctnnb1, and human renal malignancies had similar mRNA expression signatures and were associated with activation of networks centered on β-catenin and TP53. Up-regulation of WNT/β-catenin targets (MYC, Survivin, FOXA2, Axin2 and Cyclin D1) was confirmed by immunoblot. K-RAS/β-catenin murine kidney tumors were more similar to human Wilms tumor than to other renal malignancies and demonstrated activation of a TP53 dependent network of genes, including the transcription factor E2F1. Up-regulation of E2F1 was confirmed in murine and human Wilms tumor samples.Simultaneous activation of K-RAS and β-catenin in embryonic renal epithelium leads to neoplasms similar to human Wilms tumor and associated with activation of TP53 and up-regulation of E2F1. Further studies are warranted to evaluate the role of TP53 and E2F1 in human Wilms tumor.
- Published
- 2015
- Full Text
- View/download PDF
48. Novel Simulation Model of Non-Muscle Invasive Bladder Cancer: A Platform for a Virtual Randomized Trial of Conservative Therapy vs. Cystectomy in BCG Refractory Patients
- Author
-
Badri Rengarajan, Wade J. Sexton, Joyce Noah-Vanhoucke, Peter E. Clark, Sanjay R Patel, Gary D. Steinberg, Ashish M. Kamat, Kevin W. Mayo, Tuan A. Dinh, and Cheryl T. Lee
- Subjects
Research Report ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Population ,law.invention ,Cystectomy ,Randomized controlled trial ,Refractory ,law ,Surveillance, Epidemiology, and End Results ,Medicine ,education ,mitomycin C ,virtual clinical trial ,education.field_of_study ,Bladder cancer ,business.industry ,BCG failure ,Mitomycin C ,medicine.disease ,Bladder Cancer ,Surgery ,Clinical trial ,Oncology ,business - Abstract
Introduction: There have been no randomized controlled trials (RCTs) evaluating the clinical or economic benefit of mitomycin C intravesical therapy vs. radical cystectomy in patients with high-risk non-muscle invasive bladder cancer (NMIBC). We used the Archimedes computational model to simulate RCT comparing radical cystectomy versus intravesical mitomycin C (MMC) therapy to evaluate the clinical and economic outcomes for BCG-refractory NMIBC as well demonstrate the utility of computer based models to simulate a clinical trial. Methods: The Archimedes model was developed to generate a virtual population using the Surveillance Epidemiology and End Results database, other clinical trials, and expert opinions. Patients selected were diagnosed with NMIBC (
- Published
- 2015
- Full Text
- View/download PDF
49. Renal cell cancer histological subtype distribution differs by race and sex
- Author
-
S. Duke Herrell, Daniel A. Barocas, Sam S. Chang, Matthew J. Resnick, Loren Lipworth, Joseph A. Smith, Alicia K. Morgans, Peter E. Clark, David F. Penson, and Todd L. Edwards
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,business.industry ,Urology ,medicine.medical_treatment ,Incidence (epidemiology) ,030232 urology & nephrology ,Chromophobe cell ,Odds ratio ,urologic and male genital diseases ,medicine.disease ,female genital diseases and pregnancy complications ,Nephrectomy ,Confidence interval ,End stage renal disease ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,Body mass index - Abstract
Objectives To examine racial differences in the distribution of histological subtypes of renal cell carcinoma (RCC) and associations with established RCC risk factors by subtype. Materials and Methods Tumours from 1532 consecutive patients with RCC who underwent nephrectomy at Vanderbilt University Medical Center (1998–2012) were classified as clear-cell, papillary, chromophobe and other subtypes. In pairwise comparisons, we used multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between race, sex, age, end-stage renal disease (ESRD) and body mass index at diagnosis according to histological subtype. Results The RCC subtype distribution was significantly different in black people from that in white people (P < 0.001), with a substantially higher proportion of patients with papillary RCC among black people than white people (35.7 vs 13.8%). In multivariate analyses, compared with clear-cell RCC, people with papillary RCC were significantly more likely to be black (OR 4.15; 95% CI 2.64–6.52) and less likely to be female (OR 0.60; 95% CI 0.43–0.83). People with chromophobe RCC were significantly more likely to be female (OR 2.32; 95% CI 1.44–3.74). Both people with papillary RCC (OR 6.26; 95% CI 2.75–14.24) and those with chromophobe RCC (OR 7.07; 95% CI 2.13–23.46) were strongly and significantly more likely to have ESRD, compared with those with clear-cell RCC. Conclusion We observed marked racial differences in the proportional subtype distribution of RCCs diagnosed at a large tertiary care academic centre. To our knowledge, no previous study has examined racial differences in the distribution of RCC histologies while adjusting for ESRD, which was the factor most strongly associated with papillary and chromophobe RCC compared with clear-cell RCC.
- Published
- 2015
- Full Text
- View/download PDF
50. Follow-up imaging in the first two years after nephrectomy for T1 RCC: Over-use or necessary care?
- Author
-
Matthew J. Resnick, Daniel Sun, Joseph A. Smith, William Sohn, Michael S. Cookson, S. Joshi, Daniel A. Barocas, Sam S. Chang, and Peter E. Clark
- Subjects
medicine.medical_specialty ,business.industry ,Urology ,medicine.medical_treatment ,Concordance ,030232 urology & nephrology ,Logistic regression ,medicine.disease ,Rate ratio ,Stage t1 ,Nephrectomy ,Surgery ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Renal cell carcinoma ,030220 oncology & carcinogenesis ,medicine ,symbols ,Radiology ,Poisson regression ,Single institution ,business - Abstract
Objective: We sought to study patterns of imaging for follow-up after surgery for stage T1 renal cell carcinoma (RCC) at a single institution. We hypothesised that there would be significant variation in the use of surveillance imaging. Methods and materials: We evaluated the two-year follow-up of 317 consecutive patients undergoing radical or partial nephrectomy who were found to have pT1 RCC. Follow-up imaging data were collected. Surgical characteristics and tumour pathology data were analysed via a Poisson regression model to evaluate the incidence rate ratio for frequency of imaging based on each variable. Logistic regression was used to evaluate factors correlated with concordance with current imaging guidelines. Results: A total of 1016 imaging exams were performed after surgery on 268 patients. These studies identified four tumour recurrences: two local and two lung. The overall recurrence rate was 1.49%. Three recurrences were found within a two-year postoperative window, and one was recorded on the patient’s last clinic note after two years. Of 66 imaging exams with findings suspicious for recurrence, 62 were found to be false positives. All statistical analyses on a subgroup of 162 patients with full two-year follow-up failed to demonstrate any correlation between clinicopathologic variables and the frequency of abdominal imaging or concordance with current imaging guidelines. Conclusions: Frequent follow-up imaging studies were obtained despite a low recurrence rate. There was a high rate of false-positive findings on routine exams. No clinicopathologic criteria were identified that were correlated with increased imaging frequency.
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.