Urology Commons^™

Prevalence And Relevant Factors Of Nocturia And Its Impact On Sleep Quality In Chinese University Students, Yakai Liu, Zhenwei Zhang, Huijie Hu, Xiangfei He, Pengchao Xu, Qifeng Dou, Cuiping Song, Huiqing Zhang, Israel Franco, Konstantinos Kamperis, Søren Rittig, Jianguo Wen

Faculty, Staff and Student Publications

The purpose of this study was to investigate the prevalence and relevant factors of nocturia and its impact on sleep quality in university students in Mainland China. A large-scale survey was conducted on 14,000 university students from 3 universities in Henan province, China by using an anonymous questionnaire. The questionnaire collected the information from the past six months. The relationships between the prevalence of nocturia and its relevant factors were evaluated. A total of 13,874 questionnaires were collected and 13,104 qualified for statistical analysis. A total of 659 students suffered from clinically relevant nocturia (CRN) (4.56% in male and 5.34% …

Barriers To And Facilitators Of Paediatric Medical Device Innovation: A Scoping Review Protocol, Lynn Kysh, Grzegorz Zapotoczny, Lisa Manzanete, Megan Carey, Payal Shah, Francesca Joseph, Haley Kempf, Abu Taher Sikder, Julia Finkel, Usha Thekkedath, Kara Toman, Chester J Koh, Kolaleh Eskandanian, Juan Espinoza

Faculty, Staff and Students Publications

INTRODUCTION: The development of paediatric medical devices continues to lag adult medical devices and contributes to issues of inequity, safety, quality and patient outcomes. New legislation and funding mechanisms have been introduced over the past two decades, but the gap remains. Clinical trials have been identified as a pain point, but components of effective clinical research infrastructure are poorly understood. As part of a multimodal research strategy, the Pediatric Device Consortia (PDC) will conduct a scoping review to better understand infrastructural barriers to and facilitators of paediatric medical device clinical research identified in the health sciences literature.

METHODS AND ANALYSIS: …

Practical Guidance On Establishing A Molecular Testing Pathway For Alterations In Homologous Recombination Repair Genes In Clinical Practice For Patients With Metastatic Prostate Cancer, Martin Schostak, Angela Bradbury, Alberto Briganti, David Gonzalez, Leonard Gomella, Joaquin Mateo, Frédérique Penault-Llorca, Albrecht Stenzinger, Alexander Wyatt, Anders Bjartell

Department of Urology Faculty Papers

CONTEXT: Prostate cancer is a molecularly heterogeneous disease that is amenable to diagnostic testing to identify patients potentially eligible for personalised treatments inform familial risk and provide relevant information about potential prognosis. Several guidelines support the integration of genomic testing in a shared decision-making framework so that both health care professionals (HCPs) and patients are involved in determining the best treatment approach.

OBJECTIVE: To review current guidelines on molecular diagnostic testing for homologous recombination repair (HRR) gene alterations in patients with metastatic prostate cancer, with the aim of providing practical considerations for effective guideline implementation and establishment of an appropriate …

Specific Gravity Improves Identification Of Clinically Significant Quantitative Proteinuria From The Dipstick Urinalysis, Meredith C Mcadams, L Parker Gregg, Pin Xu, Song Zhang, Michael Li, Ella Carroll, Vaishnavi Kannan, Duwayne L Willett, S Susan Hedayati

Faculty, Staff and Students Publications

KEY POINTS: Urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio are frequently obtained and represent possible tools for screening for proteinuria and thus early CKD. Adding specific gravity to dipstick proteinuria improves the ability to screen patients with clinically significant proteinuria and can be used to identify patients with early CKD.

BACKGROUND: CKD is often underdiagnosed during early stages when GFR is preserved because of underutilization of testing for quantitative urine albumin-to-creatinine ratio (UACR) or urine protein-to-creatinine ratio (UPCR). Semiquantitative dipstick proteinuria (DSP) on urinalysis is widely obtained but not accurate for identifying clinically significant proteinuria.

METHODS: We identified all patients …

Loss Of Lpar6 And Cab39l Dysregulates The Basal-To-Luminal Urothelial Differentiation Program, Contributing To Bladder Carcinogenesis, Sangkyou Lee, Jolanta Bondaruk, Yishan Wang, Huiqin Chen, June Goo Lee, Tadeusz Majewski, Rachel D Mullen, David Cogdell, Jiansong Chen, Ziqiao Wang, Hui Yao, Pawel Kus, Joon Jeong, Ilkyun Lee, Woonyoung Choi, Neema Navai, Charles Guo, Colin Dinney, Keith Baggerly, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Marek Kimmel, Peng Wei, Bogdan Czerniak

Faculty, Staff and Student Publications

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term "forerunner" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two …

Risks Of Depression, Anxiety, And Suicide In Partners Of Men With Prostate Cancer: A National Cohort Study, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Alexis C Edwards, Kristina Sundquist, Weiva Sieh

Faculty, Staff and Student Publications

BACKGROUND: A diagnosis of prostate cancer (PC) may cause psychosocial distress not only in a man but also in his intimate partner. However, long-term risks of depression, anxiety, or suicide in partners of men with PC are largely unknown.

METHODS: A national cohort study was conducted of 121 530 partners of men diagnosed with PC during 1998-2017 and 1 093 304 population-based controls in Sweden. Major depression, anxiety disorder, and suicide death were ascertained through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors.

RESULTS: Partners of men with high-risk PC had increased risks …

Efficacy Of Intravesical Nadofaragene Firadenovec For Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From A Phase 3 Trial, Vikram M. Narayan, Stephen A. Boorjian, Mehrdad Alemozaffar, Badrinath R. Konety, Neal D. Shore, Leonard G. Gomella, Ashish M. Kamat, Trinity J. Bivalacqua, Jeffrey S. Montgomery, Seth P. Lerner, Joseph E. Busby, Michael Poch, Paul L. Crispen, Gary D. Steinberg, Anne K. Schuckman, Tracy M. Downs, Joseph Mashni, Brian R. Lane, Thomas J. Guzzo, Gennady Bratslavsky, Lawrence I. Karsh, Michael E. Woods, Gordon Brown, Daniel Canter, Adam Luchey, Yair Lotan, Brant A. Inman, Michael B. Williams, Michael S. Cookson, Sam S. Chang, Alexander I. Sankin, Michael A. O'Donnell, David Sawutz, Richard Philipson, Nigel R. Parker, Seppo Yla-Herttuala, Dorte Rehm, Jørn S. Jakobsen, Kristian Juul, Colin P.N. Dinney

Department of Urology Faculty Papers

Purpose: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector–based gene therapy for bacillus Calmette-Guérin (BCG)–unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up.

Materials and Methods: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence–free (HGRF).

Results: One hundred fifty-seven …

Voiding Phase Dysfunction In Multiple Sclerosis: Contemporary Review Of Terminology, Diagnosis, Management, And Future Directions, Catherine Frances Ingram, John A Lincoln, Rose Khavari

Faculty, Staff and Student Publications

Lower urinary tract symptoms (LUTS) are highly prevalent in individuals with multiple sclerosis (MS). However, assessment of these symptoms is often hindered by vague definitions or absence of screening in asymptomatic patients. It is crucial to exercise caution when applying the non-neurogenic definition of urinary retention in this population. For men with MS experiencing persistent and treatment-resistant LUTS, urodynamic studies should be used to identify the underlying causes of symptoms. Although numerous therapies are presently accessible for managing LUTS in MS, there is a need for further investigation into emerging treatments such as percutaneous tibial nerve, and noninvasive brain stimulation.

Piezo1 Regulates Meningeal Lymphatic Vessel Drainage And Alleviates Excessive Csf Accumulation, Dongwon Choi, Eunkyung Park, Joshua Choi, Renhao Lu, Jin Suh Yu, Chiyoon Kim, Luping Zhao, James Yu, Brandon Nakashima, Sunju Lee, Dhruv Singhal, Joshua P Scallan, Bin Zhou, Chester J Koh, Esak Lee, Young-Kwon Hong

Faculty, Staff and Students Publications

Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of …

Objective Assessment Of Rupture Parameters In Intact And Acute Post-Cystorrhaphy Cadaveric Bladders, Geoffrey D. Towers, Dani G. Zoorob, Rose A. Maxwell, Ashley N. Reid, Jerome L. Yaklic, Jason C. Massengill

Obstetrics and Gynecology Faculty Publications

Background: Certain procedures, particularly those used to treat symptoms of bladder pain syndrome/interstitial cystitis (BPS/IC), involve filling the bladder to or over its capacity for visualization and/or relief of symptoms. Rarely, if excessive pressure or volume is used, bladders may rupture causing significant harm to the patient. The purpose of this study was to identify baseline data for pressure and volume when hydrodistention is attempted in explanted cadaveric bladders, as well as determine bladder rupture pressure changes in the acute post-cystorrhaphy state. Methods: Eight explanted cadaveric bladders were filled using a systematic digital pump system. Intravesical pressure and volume were …

Target: A Randomized, Noninferiority Trial Of A Pretest, Patient-Driven Genetic Education Webtool Versus Genetic Counseling For Prostate Cancer Germline Testing, Stacy Loeb, Scott Keith, Heather Cheng, Amy Leader, Laura Gross, Tatiana Sanchez Nolasco, Nataliya Byrne, Rebecca Hartman, Lauren Brown, Christopher Pieczonka, Leonard Gomella, William Kevin Kelly, Costas Lallas, Nathan Handley, Patrick Mille, James Mark, Gordon Brown, Sameer Chopra, Alexandra Mcclellan, David Wise, Lucas Hollifield, Veda Giri

Department of Urology Faculty Papers

PURPOSE: Germline genetic testing (GT) is important for prostate cancer (PCA) management, clinical trial eligibility, and hereditary cancer risk. However, GT is underutilized and there is a shortage of genetic counselors. To address these gaps, a patient-driven, pretest genetic education webtool was designed and studied compared with traditional genetic counseling (GC) to inform strategies for expanding access to genetic services.

METHODS: Technology-enhanced acceleration of germline evaluation for therapy (TARGET) was a multicenter, noninferiority, randomized trial (ClinicalTrials.gov identifier: NCT04447703) comparing a nine-module patient-driven genetic education webtool versus pretest GC. Participants completed surveys measuring decisional conflict, satisfaction, and attitudes toward GT at …

Spectrophotometric Analysis Of Purple Urine Secondary To Methylene Blue And Hydroxocobalamin Co-Administration, Jeremy Hardin, Henrik Galust, Richard Franklin Clark, Binh Ly, Raymond Theodore Suhandynata

Faculty, Staff and Student Publications

BACKGROUND: The development of purple urine after methylene blue (methylthioninium chloride) and hydroxocobalamin co-administration is a rare clinical entity that has not been fully elucidated. A 47-year-old male presented to the emergency department with hypotension, cyanosis, and depressed mental status. The patient was noted to have profound peripheral and central cyanosis, as well as chocolate-colored arterial blood. He was treated with both methylene blue and hydroxocobalamin and developed purple urine for approximately 1 week.

METHODS: Color chromatography was performed by placing the patient's urine directly onto absorbent filter paper. Urine spectrophotometry was performed utilizing the NanoDrop One/One C UV-Vis Spectrophotometer. …

Validation Of Distinct Bladder Pain Phenotypes Utilizing The Mapp Research Network Cohort, Oluwarotimi Sewedo Nettey, Cindy Gu, Nicholas James Jackson, A Lenore Ackerman

Faculty, Staff and Students Publications

Introduction and hypothesis: As interstitial cystitis/bladder pain syndrome (IC/BPS) likely represents multiple pathophysiologies, we sought to validate three clinical phenotypes of IC/BPS patients in a large, multi-center cohort using unsupervised machine learning (ML) analysis.

Methods: Using the female Genitourinary Pain Index and O'Leary-Sant Indices, k-means unsupervised clustering was utilized to define symptomatic phenotypes in 130 premenopausal IC/BPS participants recruited through the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network. Patient-reported symptoms were directly compared between MAPP ML-derived phenotypic clusters to previously defined phenotypes from a single center (SC) cohort.

Results: Unsupervised ML categorized IC/BPS participants into …

The Il6/Jak/Stat3 Signaling Axis Is A Therapeutic Vulnerability In Smarcb1-Deficient Bladder Cancer, Chandra Sekhar Amara, Karthik Reddy Kami Reddy, Yang Yuntao, Yuen San Chan, Danthasinghe Waduge Badrajee Piyarathna, Lacey Elizabeth Dobrolecki, David J H Shih, Zhongcheng Shi, Jun Xu, Shixia Huang, Matthew J Ellis, Andrea B Apolo, Leomar Y Ballester, Jianjun Gao, Donna E Hansel, Yair Lotan, H Courtney Hodges, Seth P Lerner, Chad J Creighton, Arun Sreekumar, W Jim Zheng, Pavlos Msaouel, Shyam M Kavuri, Nagireddy Putluri

Faculty, Staff and Student Publications

SMARCB1 loss has long been observed in many solid tumors. However, there is a need to elucidate targetable pathways driving growth and metastasis in SMARCB1-deficient tumors. Here, we demonstrate that SMARCB1 deficiency, defined as genomic SMARCB1 copy number loss associated with reduced mRNA, drives disease progression in patients with bladder cancer by engaging STAT3. SMARCB1 loss increases the chromatin accessibility of the STAT3 locus in vitro. Orthotopically implanted SMARCB1 knockout (KO) cell lines exhibit increased tumor growth and metastasis. SMARCB1-deficient tumors show an increased IL6/JAK/STAT3 signaling axis in in vivo models and patients. Furthermore, a pSTAT3 selective inhibitor, TTI-101, reduces …

Regulation Of Androgen Receptor Stability By The Β1pix/Stub1 Complex, Ahmed Chahdi, Carolina Jorgez, Abhishek Seth

Faculty, Staff and Students Publications

The Androgen Receptor (AR) is essential in the development and differentiation of testes and male genitalia. AR expression is tightly regulated at the translational and posttranslational levels. AR posttranscriptional regulation is a major determinant of AR availability since AR is a direct target of E3 ubiquitin ligase STUB1. Our work indicated that the Rac/Cdc42 guanosine triphosphatase guanine nucleotide exchange factor, β1Pix, enhanced AR levels after AR stimulation in HEK293 and HeLa cells. AR stimulation decreased AR ubiquitination which is accompanied by increased β1Pix binding to AR. Ectopic expression of β1Pix decreased AR ubiquitination in Tm4 and HEK293 cells. We demonstrated …

Evaluating Noninvasive Brain Stimulation To Treat Overactive Bladder In Individuals With Multiple Sclerosis: A Randomized Controlled Trial Protocol, Betsy H Salazar, Kristopher A Hoffman, John A Lincoln, Christof Karmonik, Hamida Rajab, Santosh A Helekar, Rose Khavari

Faculty, Staff and Student Publications

Background

Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD.

Methods

By employing an advanced neuro-navigation …

High Expression Of Trop2 Is Associated With Aggressive Localized Prostate Cancer And Is A Candidate Urinary Biomarker, Shiqin Liu, Sarah J Hawley, Christian A Kunder, En-Chi Hsu, Michelle Shen, Lennart Westphalen, Heidi Auman, Lisa F Newcomb, Daniel W Lin, Peter S Nelson, Ziding Feng, Maria S Tretiakova, Lawrence D True, Funda Vakar-Lopez, Peter R Carroll, Jeffry Simko, Martin E Gleave, Dean A Troyer, Jesse K Mckenney, James D Brooks, Michael A Liss, Tanya Stoyanova

Faculty, Staff and Student Publications

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and …

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance And Immune Evasion In Lethal Prostate Cancer, Sandra Santasusagna, Shijia Zhu, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Adam Ertel, Saioa Garcia-Longarte, Won-Min Song, Naoto Fujiwara, Peiyao Li, Isabel Mendizabal, Daniel P. Petrylak, William Kevin Kelly, E. Premkumar Reddy, Liguo Wang, Matthew J. Schiewer, Amaia Lujambio, Jeffrey Karnes, Karen E. Knudsen, Carlos Cordon-Cardo, Haidong Dong, Haojie Huang, Arkaitz Carracedo, Yujin Hoshida, Veronica Rodriguez-Bravo, Josep Domingo-Domenech

Department of Medical Oncology Faculty Papers

Signaling rewiring allows tumors to survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprogramming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5' untranslated regions. Indeed, translation of the androgen receptor and major histocompatibility complex I (MHC-I) through this motif …

Comparative Study Between Antegrade Flexible Ureteroscopy And Reterograde Intrarenal Surgery In The Management Of Impacted Upper Ureteric Stones 15 Cm Or Larger, Ahmed Mohey, Ahmed A Abdelfattah, Ahmed E Mohammed, Abdelmoniem Marzouk, Amr S El-Dakhakhny

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate the safety and efficacy of antegrade flexible ureteroscopy (FURS) with the following criteria (supine, ultrasonic guided puncture through lower calyx with 14 fr tract, tubeless) versus retrograde intrarenal surgery (RIRS) in the management of large impacted upper ureteric stones ≥ 1.5 cm.

PATIENTS AND METHODS: This study recruited 61 patients with single large impacted upper ureteric stone of ≥ 1.5 cm. The patients were randomly allocated to two groups. Group A, included 31 patients who treated by antegrade FURS, all patients were put in supine modified galadako Valdivia position and the renal access is reached by …

Impact Of Routine Urine Cultures On Antibiotic Usage In Those Undergoing A Routine Annual Spinal Cord Injury Evaluation, Sarah May, Annette Walder, Casey Hines-Munson, Ivy Poon, S Ann Holmes, Charlesnika T Evans, Barbara W Trautner, Felicia Skelton

Faculty, Staff and Students Publications

OBJECTIVE: The Veterans Health Administration (VHA), the largest single provider of spinal cord injury and disorder (SCI/D) care in the United States, currently mandates that every patient receives a screening urine culture during the annual evaluation, a yearly comprehensive history and physical examination. This testing has shown in a small subset of patients to overidentify asymptomatic bacteriuria that is then inappropriately treated with antibiotics. The objective of the current analysis was to assess the association of the annual evaluation on urine testing and antibiotic treatment in a national sample of Veterans with SCI/D.

DESIGN/METHOD: A retrospective cohort study using national …

Targeting The Αvβ3/Ngr2 Pathway In Neuroendocrine Prostate Cancer, Anna Testa, Fabio Quaglia, Nicole M. Naranjo, Cecilia E. Verrillo, Christopher D. Shields, Stephen Lin, Maxwell W. Pickles, Drini F. Hamza, Tami Von Schalscha, David A. Cheresh, Benjamin E Leiby, Qin Liu, Jianyi Ding, William K. Kelly, D. Craig Hooper, Eva Corey, Edward F. Plow, Dario C. Altieri, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in …

Chronic Inflammation Can Transform The Fate Of Normal And Mutant Hematopoietic Stem Cells, Jingjing Li, Camille Malouf, Linde A Miles, Mara B Willis, Eric M Pietras, Katherine Y King

Faculty, Staff and Students Publications

Chronic inflammation, although subtle, puts the body in a constant state of alertness and is associated with many diseases, including cancer and cardiovascular diseases. It leads hematopoietic cells to produce and release proinflammatory cytokines, which trigger specific signaling pathways in hematopoietic stem cells (HSCs) that cause changes in proliferation, differentiation, and migration. This response is essential when HSCs are needed to produce specific blood cells to eliminate an intruder, such as a pathogenic virus, but mutant HSCs can use these proinflammatory signals to their advantage and accelerate the development of hematologic disease or malignancy. Understanding this complex process is vital …

Sigma1 Regulates Lipid Droplet-Mediated Redox Homeostasis Required For Prostate Cancer Proliferation, Halley Oyer, Alexandra Steck, Charles Longen, Sanjana Venkat, Konuralp Bayrak, Eleanor Munger, Dan Fu, Paola Castagnino, Christina Sanders, Nathalia Tancler, My Mai, Justin Myers, Matthew Schiewer, Nan Chen, Elahe Mostaghel, Felix Kim

Department of Urology Faculty Papers

UNLABELLED: Lipid droplets (LD) are dynamic organelles that serve as hubs of cellular metabolic processes. Emerging evidence shows that LDs also play a critical role in maintaining redox homeostasis and can mitigate lipid oxidative stress. In multiple cancers, including prostate cancer, LD accumulation is associated with cancer aggressiveness, therapy resistance, and poor clinical outcome. Prostate cancer arises as an androgen receptor (AR)-driven disease. Among its myriad roles, AR mediates the biosynthesis of LDs, induces autophagy, and modulates cellular oxidative stress in a tightly regulated cycle that promotes cell proliferation. The factors regulating the interplay of these metabolic processes downstream of …

Xaluritamig, A Steap1 × Cd3 Xmab 2+1 Immune Therapy For Metastatic Castration-Resistant Prostate Cancer: Results From Dose Exploration In A First-In-Human Study, William K. Kelly, Daniel C. Danila, Chia-Chi Lin, Jae-Lyun Lee, Nobuaki Matsubara, Patrick J. Ward, Andrew J. Armstrong, David Pook, Miso Kim, Tanya B. Dorff, Stefanie Fischer, Yung-Chang Lin, Lisa G. Horvath, Christopher Sumey, Zhao Yang, Gabor Jurida, Kristen M. Smith, Jamie N. Connarn, Hweixian L. Penny, Julia Stieglmaier, Leonard J. Appleman

Kimmel Cancer Center Faculty Papers

ABSTRACT : Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during …

Index Of Consciousness Monitoring During General Anesthesia May Effectively Enhance Rehabilitation In Elderly Patients Undergoing Laparoscopic Urological Surgery: A Randomized Controlled Clinical Trial, Fengling Qi, Long Fan, Chunxiu Wang, Yang Liu, Shuyi Yang, Zhen Fan, Fangfang Miao, Minhui Kan, Kunpeng Feng, Tianlong Wang

Faculty, Staff and Student Publications

Background: Based on electroencephalogram (EEG) analysis, index of consciousness (IoC) monitoring is a new technique for monitoring anesthesia depth. IoC is divided into IoC1 (depth of sedation) and IoC2 (depth of analgesia). The potential for concurrent monitoring of IoC1 and IoC2 to expedite postoperative convalescence remains to be elucidated. We investigated whether combined monitoring of IoC1 and IoC2 can effectively enhances postoperative recovery compared with bispectral index (BIS) in elderly patients undergoing laparoscopic urological surgery under general anesthesia.

Methods: In this prospective, controlled, double-blinded trail, 120 patients aged 65 years or older were arbitrarily assigned to either the IoC group …

Evaluating Atezolizumab In Patients With Urinary Tract Squamous Cell Carcinoma (Aurora): Study Protocol For A Single Arm, Open-Label, Multicentre, Phase Ii Clinical Trial, Simon Crabb, Robin Wickens, Sarah Jane-Bibby, Denise Dunkley, Megan Lawrence, Allen Knight, Robert Jones, Alison Birtle, Robert Huddart, Mark Linch, Jonathan Martin, Adam Coleman, Konstantinos Boukas, Hannah Markham, Gareth Griffiths

Faculty, Staff and Student Publications

BACKGROUND: Bladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease. We have yet to establish definitive systemic treatment options for advanced UTSCC. Preliminary translational data, from UTSCC patient tumour samples, indicate high PD-L1 expression and tumour infiltrating lymphocytes in a proportion of cases. Both of these features are associated with differential gene …

Cytoreductive Nephrectomy For Patients With Metastatic Sarcomatoid And/Or Rhabdoid Renal Cell Carcinoma Treated With Immune Checkpoint Therapy, Andrew W Hahn, Ritesh R Kotecha, Paul V Viscuse, Alberto C Pieretti, Andrew J Wiele, Eric Jonasch, Chung-Han Lee, Jianjun Gao, Amado J Zurita, Amishi Y Shah, Matthew T Campbell, Padmanee Sharma, Robert J Motzer, Paul Russo, Christopher G Wood, Nizar M Tannir, Martin H Voss, Jose A Karam, A Ari Hakimi, Pavlos Msaouel

Faculty, Staff and Student Publications

BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is a highly aggressive tumor with a poor prognosis. Immune checkpoint therapy (ICT) has shown significant treatment efficacy in this subtype. There remains uncertainly regarding the role of cytoreductive nephrectomy (CN) for patients with metastatic RCC (mRCC) with S/R who received ICT.

OBJECTIVE: Here, we report the outcomes with ICT for patients with mRCC and S/R dedifferentiation by CN status.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted of 157 patients with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who received an ICT-based regimen at two cancer centers. …

Long-Term Risks Of Depression And Suicide Among Men With Prostate Cancer: A National Cohort Study, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Anna Bill-Axelson, Alexis C Edwards, Kristina Sundquist, Weiva Sieh

Faculty, Staff and Student Publications

BACKGROUND: A diagnosis of prostate cancer (PC) may cause psychosocial distress that worsens quality of life; however, long-term mental health outcomes are unclear.

OBJECTIVE: To determine the long-term risks of major depression and death by suicide in a large population-based cohort.

DESIGN, SETTING, AND PARTICIPANTS: This was a national cohort study of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched, population-based, control men in Sweden.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Major depression and death by suicide were ascertained from nationwide outpatient, inpatient, and death records up to 2018. Cox regression was used to compute hazard …

Implantable Penile Prosthesis For Erectile Dysfunction: Insurance Coverage In The United States, Mohit Khera, Joshua P Langston, Matthew E Pollard, Denise Asafu-Adjei, Natalie C Edwards, Krista D Nitschelm, Mital Patel, Samir K Bhattacharyya

Faculty, Staff and Students Publications

Introduction: A manufacturer's benefit verification database was evaluated to ascertain United States health plan insurance coverage for implantable penile prostheses for erectile dysfunction.

Methods: All-payer and employer-sponsored health plan benefit verification databases were queried to determine implantable penile prosthesis approval status. For the all-payer analysis, data by payer were available and presented for 2019-2021 to assess approval status varied by payer and over time. For the employer-sponsored health plan analysis, data by payer were available from 2018-2021.

Results: Benefit verification records for the all-payer database were available for 3,167 patients in 2019, 3,016 in 2020, and 2,837 in 2021. Insurance …

Urachal Xanthogranuloma: A Rare But Important Case Presenting As A Urachal Mass, Kunal Jain, Esha Jain, Richard Dilena, Rola Saleeb, Umesh Jain

Faculty, Staff and Student Publications

BACKGROUND: A urachal mass is a relatively rare presentation to the urologists' practice, often requiring radical surgical excision for a definitive diagnosis. Xanthogranulomatous inflammation of the urachus is an extremely rare entity with few cases reported worldwide, and to the best of our knowledge, no cases reported in the western world.

CASE PRESENTATION: In this case, a 55-year-old male patient presented with bothersome lower urinary tract symptoms and computed tomography findings demonstrating a urachal mass that was worrisome for urachal carcinoma. Following surgical intervention, histopathology revealed urachal xanthogranuloma. Post-operatively, the patient recovered well, and eventually, he had symptomatic and radiologic …