The following is a comprehensive list of Yale Urology faculty contributions to the field, as represented in their published work for the 4th quarter of calendar year 2022. The listing is separated into primary and secondary faculty sections, then in descending published date order. Each reference includes cite details and at least portions of each abstract/summary.
PRIMARY FACULTY
Constantine ML, Rockwood T, Rickey L, Bavendam T, Kane Low L, Lowder JL, Markland AD, Mcgwinn G, Mueller ER, Newman DK, Putnam S, Rudser K, Smith A, Stapleton A, Miller J, Lukacz ES; Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. Validation of Novel Bladder Health Scales and Function Indices for Women's Research. Am J Obstet Gynecol. 2022 Dec 31:S0002-9378(22)02605-9. doi: 10.1016/j.ajog.2022.12.319. Epub ahead of print. PMID: 36596439.
Conclusion: The paper and electronic forms of the Bladder Health Scales and Function Indices are reliable and valid measures of bladder health for use in women's health research.
Rahman SN, Lokeshwar SD, Syed JS, Javier-Desloges JF, Press BH, Choksi AU, Rajwa P, Pradere B, Ploussard G, Kim JW, Monaghan TF, Renzulli JR, Shariat SF, Leapman MS. Oncologic outcomes of neoadjuvant chemotherapy in patients with micropapillary variant urothelial carcinoma of the bladder. Urol Oncol. 2022 Dec 5:S1078-1439(22)00317-9. doi: 10.1016/j.urolonc.2022.09.008. Epub ahead of print. PMID: 36481253.
Background: There is lack of consensus about the effectiveness of neoadjuvant platinum-based chemotherapy in patients with micropapillary variant urothelial carcinoma (MVUC) prior to radical cystectomy. We studied the association between neoadjuvant chemotherapy (NAC) and pathologic response (PR) among patients with micropapillary versus non-variant bladder urothelial carcinoma (UC).
Nagaya N, [Sterling J, Kim IY]. Extended versus standard pelvic lymph node dissection yields no difference in 3-year biochemical recurrence rates. Prostate international. 12/2022. doi: 10.1016/j.prnil.2022.12.005.
Background: Extended pelvic lymph node dissection (ePLND) increases the detection rate of lymph node positive prostate cancer compared to a standard pelvic lymph node dissection (sPLND). However, improvement of patient outcomes remains questionable. Here we report and compare 3-year postoperative PSA recurrence rates between patients that underwent sPLND versus ePLND at the time of prostatectomy.
Burgio KL, Cunningham SD, Newman DK, Low LK, Nodora J, Lipman TH, Gahagan S, Klusaritz H, James AS, Rickey L, Kenton KS, Hebert-Beirne J, Williams BR; Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. Need for Public Health Messaging Related to Bladder Health from Adolescence to Advanced Age. J Womens Health (Larchmt). 2022 Nov 28. doi: 10.1089/jwh.2022.0185. Epub ahead of print. PMID: 36454206.
Results: Forty-four focus groups were conducted with 360 participants organized into six age groups (11-93 years). There was consensus across age groups that more information about the bladder is wanted and needed throughout the life course, as there is currently a lack of reliable educational resources … participants also saw value in educating the general public regardless of risk status. They also recommended education for parents and teachers who are in positions to control bathroom access.
[Kim J]. The binding sites of E2F transcription factor in drosophila metabolic genes are functionally distinct. bioRxiv. 2022.
… Remarkably, chromatin accessibility was significantly reduced at multiple genomic regions. Collectively, our results illustrate how the pleiotropic effects on metabolism, gene expression and development in the PgkΔE2F animals underscore the importance of E2F regulation on a single E2F target, Pgk.
Kim WT, Kim J, Kim WJ. How can we best manage biochemical failure after radical prostatectomy? Investig Clin Urol. 2022 Nov;63(6):592-601. doi: 10.4111/icu.20220294. PMID: 36347548; PMCID: PMC9643724.
Biochemical recurrence (BCR) is common after radical prostatectomy, but effective treatment options for men with BCR after curative treatment remain controversial. Although prostate-specific antigen is widely used as a surrogate marker for prostate cancer survival, it cannot fully differentiate between prostate-cancer-specific survival and overall survival. Thus, it is challenging for physicians to determine the timing of treatment to halt or slow the clinical progression of disease in patients with BCR while avoiding overtreatment for patients whose disease may not progress beyond BCR.
Dzimitrowicz HE, Wilson LE, Jackson BE, Spees LP, Baggett CD, Greiner MA, Kaye DR, Zhang T, George D, Scales CD Jr, Pritchard JE, Leapman MS, Gross CP, Dinan MA, Wheeler SB. End-of-Life Care for Patients With Metastatic Renal Cell Carcinoma in the Era of Oral Anticancer Therapy. JCO Oncol Pract. 2022 Nov 22:OP2200401. doi: 10.1200/OP.22.00401. Epub ahead of print. PMID: 36413741.
Purpose: New therapies including oral anticancer agents (OAAs) have improved outcomes for patients with metastatic renal cell carcinoma (mRCC). However, little is known about the quality of end-of-life (EOL) care and systemic therapy use at EOL in patients receiving OAAs or with mRCC.
Smith AL, Rudser K, Harlow BL, McGwin G, Barthold J, Brady SS, Brubaker L, Cunningham SD, Griffith JW, Kenton K, Klusaritz H, Lewis CE, Lukacz ES, Maki J, Markland AD, Mueller ER, Newman DK, Nodora J, Rickey LM, Rockwood T, Simon M, Wyman JF, Sutcliffe S; Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. RISE FOR HEALTH: Rationale and protocol for a prospective cohort study of bladder health in women. Neurourol Urodyn. 2022 Nov 2. doi: 10.1002/nau.25074. Epub ahead of print. PMID: 36321762.
Methods: RISE is a population-based, multicenter, prospective longitudinal cohort study of community-dwelling, English- and Spanish-speaking adult women based in the United States. Its goal is to inform the distribution of bladder health and the individual factors (biologic, behavioral, and psychosocial) and multilevel factors (interpersonal, institutional, community, and societal) that promote bladder health and/or prevent LUTS in women across the life course. Key study development activities included the: (1) development of a conceptual framework and philosophy to guide subsequent activities, (2) creation of a study design and sampling strategy, prioritizing diversity, equity, and inclusion, and (3) selection and development of data collection components.
Ghiraldi EM, Nguyen J, Buck M, Nair H, Israel G, Singh D. Using Peritumor and Intratumor Vascularity on Preoperative Imaging to Predict Fuhrman Grade Histology of Renal Tumors. J Endourol. 2022 Nov;36(11):1489-1494. doi: 10.1089/end.2022.0069. PMID: 35670255.
Objective and Methods: To investigate if peritumor and/or intratumor vasculature is associated with high-grade tumor histology for renal cell carcinoma. A retrospective review at a tertiary care facility was performed of patients who underwent radical nephrectomy or partial nephrectomy for a renal tumor between January 2015 and December 2020. Data of tumor characteristics were collected from final pathology reports. A single radiologist specializing in genitourinary imaging reviewed all preoperative cross-sectional imaging for peritumor vessels and intratumor vessels.
Choi JE, St. Martin B, Swallow C, Rickey L, Harmanli O. Resection of Infected Sacrohysteropexy Mesh. OBG Manag. 2022 November;34(11).
Robotic resection of intra-abdominal mesh after sacrohysteropexy can be feasible by surgeons who are robotically trained and appropriate for patients who have complications from chronic mesh infection.
Honig S, Gittelman M, Kaminetsky J, Wang C, Amory JK, Rohowsky N, Dudley RE, Woun Seo B, Newmark J, Swerdloff R. Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety. J Sex Med. 2022 Dec;19(12):1750-1758. doi: 10.1016/j.jsxm.2022.09.002. Epub 2022 Oct 20. PMID: 36272969.
Background: Long-term data evaluating the efficacy and safety of oral testosterone undecanoate (oral TU; JATENZO) in adult hypogonadal men provides important information for healthcare professionals who prescribe testosterone replacement therapy (TRT).
Nabavizadeh B, Li KD, Hakam N, Shaw NM, Leapman MS, Breyer BN. Incidence of circumcision among insured adults in the United States. PLoS One. 2022 Oct 17;17(10):e0275207. doi: 10.1371/journal.pone.0275207. PMID: 36251658; PMCID: PMC9576047.
Purpose: Although circumcision is the most commonly performed surgery in males, less is known about the incidence and indications of adult circumcision. In this study, we aim to present the incidence of adult circumcision across the United States.
Swallow CH, Rickey LM, Harmanli O. Sling plication for persistent stress urinary incontinence after midurethral sling. Int Urogynecol J. 2022 Oct 15. doi: 10.1007/s00192-022-05379-z. Epub ahead of print. PMID: 36242629.
Conclusions: Sling plication is an effective and minimally invasive option to treat persistent stress urinary incontinence after failed midurethral sling procedures. It avoids additional mesh burden or more invasive retropubic surgery and should be offered as a treatment option for appropriately counseled patients.
Kim JE, Kaldany A, Lichtbroun B, Singer EA, Jang TL, Ghodoussipour S, Kim MM, Kim IY. Single-Port Robotic Radical Prostatectomy: Short-Term Outcomes and Learning Curve. J Endourol. 2022 Oct;36(10):1285-1289. doi: 10.1089/end.2021.0885. PMID: 35906798; PMCID: PMC9587764.
Conclusions: This case series confirms the safety and efficacy of single-port [SP] robot-assisted radical prostatectomy [RARP] with acceptable short-term outcomes. There is a significant learning curve for this new modality. Shorter hospital stay appears to be an early benefit of the SP platform.
You C, [Onofrey JA]. Distributed, collaborative, and federated learning, and affordable AI and healthcare for resource diverse global health third MICCAI workshop, DeCaF 2022, and second MICCAI workshop, FAIR 2022, held in conjunction with MICCAI 2022, singapore, september 18 and 22, 2022, proceedings incremental learning meets transfer learning: Application to Multi-site prostate MRI segmentation. Lecture notes in computer science. 2022:3-16. doi: 10.1007/978-3-031-18523-6_1.
In this paper, we carry out the first-of-its-kind comprehensive exploration of how to build a multi-site model to achieve strong performance on the training domains and can also serve as a strong starting point for better generalization on new domains in the clinical scenarios … Our key idea is to combine the benefits of incremental-learning (IL) and transfer-learning by sequentially training a multi-dataset expert.
SECONDARY FACULTY
Qu R, Kluger Y, Yang J, Zhao J, Hafler DA, Krause DS, Bersenev A, Bosenberg M, Hurwitz M, Lucca L, Kluger HM. Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure. Mol Cancer. 2022 Dec 14;21(1):219. doi: 10.1186/s12943-022-01688-5. PMID: 36514045; PMCID: PMC9749221.
… New clonotypes appearing in blood or tumor at disease progression were enriched for genes associated with cytotoxicity or stemness (FGFBP2, GNLY, GZMH, GZMK, IL7R, SELL and KLF2), and these might be harnessed for alternative cellular therapy or cytokine therapy. In-depth single-cell analyses of serial samples from additional ACT-treated patients is warranted, and viral- versus tumor-specificity should be carefully analyzed.
Balar AV, Castellano DE, Grivas P, Vaughn DJ, Powles T, Vuky J, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Necchi A, Petrylak DP, Plimack ER, Xu JZ, Imai K, Moreno BH, Bellmunt J, de Wit R, O'Donnell PH. Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up. Ann Oncol. 2022 Dec 6:S0923-7534(22)04760-3. doi: 10.1016/j.annonc.2022.11.012. Epub ahead of print. PMID: 36494006.
Conclusion: With ∼5 years of follow-up, pembrolizumab monotherapy continued to demonstrate durable efficacy with no new safety signals in patients with platinum-resistant metastatic UC and as first-line therapy in cisplatin-ineligible patients.
Ünlü S, Shin JJ, Par-Young J, Simonov M, Vinetz J, Petrylak DP, Kang I, Kim JW. Effect of Androgen-Androgen Receptor Directed Therapy on COVID-19 Outcome in Prostate Cancer Patients. Cancer Invest. 2022 Nov 17:1-7. doi: 10.1080/07357907.2022.2139839. Epub ahead of print. PMID: 36373994.
… While definitive conclusions cannot be made regarding outcome differences between groups due to lack of statistical significance, these data generate hypothesis that A/ARDT might shorten hospitalization stay.
Cieri N, [Braun DA]. Systematic identification of autosomal and Y-encoded minor histocompatibility antigens reveals predictors of chronic gvhd and candidate GVL targets. Blood. 11/2022;140(supplement 1):4762-4764. doi: 10.1182/blood-2022-162841.
At the core of the therapeutic effect of HLA-matched allogeneic hematopoietic cell transplantation (allo-HCT) is T cell alloreactivity against minor histocompatibility antigens (mHAgs), polymorphic peptides resulting from donor-recipient disparity at sites of single nucleotide gene polymorphisms (SNPs). Despite their crucial role in graft-versus-leukemia (GvL) and graft-versus-host disease (GvHD), only few mHAgs have been characterized to date. To systematically identify autosomal and Y-chromosome encoded HLA-I restricted mHAgs, we devised a computational pipeline … Overall, we report the generation of a robust analytic pipeline which enables the broadening of the repertoire of mHAgs available for donor selection and for predicting, monitoring or manipulating GvL and GvHD after allo-HCT.
Iorgulescu B, [Braun DA]. 115 Spatial dissection of T cell clonotype identity, transcriptional profiles, and cell-cell interactions in the tumor microenvironment and tertiary lymphoid structures. Regular and Young Investigator Award Abstracts. 11/2022:A127-A127. doi: 10.1136/jitc-2022-SITC2022.0115.
Background: Determining the spatial interactions of T cell clonotypes in tumor microenvironments and tertiary lymphoid structures (TLSs) is essential to understanding adaptive anti-tumoral immune responses, but existing spatial sequencing methods remain unable to profile the TCR repertoire at high resolution.
Mehta S, Geng B, Xu X, Harmanli O. Current state of bladder diary: a survey and review of the literature. Int Urogynecol J. 2022 Nov 2. doi: 10.1007/s00192-022-05398-w. Epub ahead of print. PMID: 36322174.
Conclusions: The literature supports the use of bladder diaries [BD]; however, many survey respondents, including fellowship-trained attendings, never or rarely use BD. Most respondents reported difficulty in using BD. More research is needed to improve the ease, accuracy, and widespread adaptation of BD use in clinical practice.
Kim JW, McKay RR, Radke MR, Zhao S, Taplin ME, Davis NB, Monk P, Appleman LJ, Lara PN Jr, Vaishampayan UN, Zhang J, Paul AK, Bubley G, Van Allen EM, Unlu S, Huang Y, Loda M, Shapiro GI, Glazer PM, LoRusso PM, Ivy SP, Shyr Y, Swisher EM, Petrylak DP. Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984. J Clin Oncol. 2022 Oct 18:JCO2102947. doi: 10.1200/JCO.21.02947. Epub ahead of print. PMID: 36256912.
Purpose: Cediranib, a pan-vascular endothelial growth factor receptor inhibitor, suppresses expression of homologous recombination repair (HRR) genes and increases sensitivity to poly-(ADP-ribose) polymerase inhibition in preclinical models. We investigated whether cediranib combined with olaparib improves the clinical outcomes of patients with prostate cancer.
Sternberg CN, Petrylak DP, Bellmunt J, Nishiyama H, Necchi A, Gurney H, Lee JL, van der Heijden MS, Rosenbaum E, Penel N, Pang ST, Li JR, García Del Muro X, Joly F, Pápai Z, Bao W, Ellinghaus P, Lu C, Sierecki M, Coppieters S, Nakajima K, Ishida TC, Quinn DI. FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression. J Clin Oncol. 2023 Jan 20;41(3):629-639. doi: 10.1200/JCO.21.02303. Epub 2022 Oct 14. PMID: 36240478.
Conclusion: To our knowledge, these are the first data to compare fibroblast growth factor receptor [FGFR]-directed therapy with chemotherapy in patients with FGFR-altered urothelial carcinoma [UC], showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/3 mRNA overexpression may be better predictors of rogaratinib response.
Schoenfeld DA, Merkin RD, Moutafi M, Martinez S, Adeniran A, Kumar D, Jilaveanu L, Hurwitz M, Rimm DL, Kluger HM. Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance. Front Oncol. 2022 Oct 13;12:990367. doi: 10.3389/fonc.2022.990367. PMID: 36313654; PMCID: PMC9608089.
While great strides have been made in the treatment of advanced renal cell carcinoma (RCC) with the emergence of immune checkpoint inhibitors (ICIs) and VEGFR-targeting drugs, sizable proportions of patients still do not respond to upfront therapy and long-term responses only occur in a minority of patients. There is therefore a great need for the development of better predictors of response and an increased understanding of mechanisms of resistance to these therapies.
Liu S, Lorgulescu JB, Li S, Borji M, Barrera-Lopez IA, Shanmugam V, Lyu H, Morriss JW, Garcia ZN, Murray E, Reardon DA, Yoon CH, Braun DA, Livak KJ, Wu CJ, Chen F. Spatial maps of T cell receptors and transcriptomes reveal distinct immune niches and interactions in the adaptive immune response. Immunity. 2022 Oct 11;55(10):1940-1952.e5. doi: 10.1016/j.immuni.2022.09.002. PMID: 36223726; PMCID: PMC9745674.
… Altogether, our method yields insights into the spatial relationships between clonality, neighboring cell types, and gene expression that drive T cell responses.
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