Patient-Derived Conditionally Reprogrammed Cells in Prostate Cancer Research.

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research.

Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure.

Heart failure (HF) is a rising global cardiovascular epidemic driven by aging and chronic inflammation. As elderly populations continue to increase, precision treatments for age-related cardiac decline are urgently needed. Here we report that cardiac and blood expression of IGFBP7 is robustly increased in patients with chronic HF and in an HF mouse model.

Insights on autophagosome-lysosome tethering from structural and biochemical characterization of human autophagy factor EPG5.

Pivotal to the maintenance of cellular homeostasis, macroautophagy (hereafter autophagy) is an evolutionarily conserved degradation system that involves sequestration of cytoplasmic material into the double-membrane autophagosome and targeting of this transport vesicle to the lysosome/late endosome for degradation. EPG5 is a large-sized metazoan protein proposed to serve as a tethering factor to enforce autophagosome-lysosome/late endosome fusion specificity, and its deficiency causes a severe multisystem disorder known as Vici syndrome. Here, we show that human EPG5 (hEPG5) adopts an extended "shepherd's staff" architecture.

The Association of Urologic Oncology Fellowship Training and Diagnostic Yield of Prostate Biopsy.

Objective: To determine the relationship between urologic oncology fellowship training (UOFT) and diagnostic yield of prostate biopsy.

Methods: Retrospective review was conducted of patients who underwent prostate biopsy across the Cleveland Clinic between 2000 and 2018. Biopsies done by urologists with and without UOFT were detailed via descriptive statistics and appropriate (chi-square, Student t, Wilcoxon rank-sum) tests.

Ureteroarterial Fistula in a Patient with an Ileal Conduit and Chronic Nephroureteral Catheter.

Ureteroarterial fistula (UAF) is a rare and potentially devastating diagnosis most often associated with a combination of pelvic oncologic or vascular surgery, radiation, and chronic ureteral stents. Herein we discuss a patient with an ileal conduit urinary diversion and left nephroureteral (NU) catheter who presented with gross hematuria and hemodynamic instability. He underwent multiple negative radiologic investigations and his clinical course highlights the need for a high index of suspicion for UAF and multidisciplinary coordination with vascular surgery and interventional radiology.

Older Age at Diagnosis and Initial Disease Volume Predict Grade Reclassification Risk on Confirmatory Biopsy in Patients Considered for Active Surveillance.

Objective: To identify which active surveillance candidates benefit most from confirmatory biopsies to exclude grade underclassification.

Materials And Methods: This observational study includes 556 men diagnosed between 2002 and 2015 with Gleason 3 + 3 (GG1) disease on initial diagnostic biopsy, of whom 406 received a confirmatory biopsy within 12 months for active surveillance. Multivariable logistic regression analysis was performed to determine clinicopathologic features associated with Gleason 7 or higher (GG2+) on a confirmatory biopsy.

Assessing the relationship between statin use and oncologic outcomes among men electing active surveillance for localized prostate cancer.

Background: This study aims to assess the effect of statin therapy on outcomes among men managed with active surveillance.

Methods: This is a retrospective cohort study evaluating 635 men managed with active surveillance from 2005 to 2015 at a large, academic medical center. The primary endpoints of analyses are disease reclassification (i.

Prognostic Factors and Risk Stratification in Invasive Upper Tract Urothelial Carcinoma.

Background: Upper tract urothelial carcinoma (UTUC) accounts for approximately 5% of all urothelial cancers. Because of similarities in morphology and histology between UTUC and urothelial carcinoma of the bladder, most treatment guidelines used for UTUC are extrapolated from the urothelial bladder carcinoma setting. With the emergence of new treatment modalities, such as immunotherapy, UTUC-specific prognostic and predictive models are needed.

Genomic Scores are Independent of Disease Volume in Men with Favorable Risk Prostate Cancer: Implications for Choosing Men for Active Surveillance.

Purpose: We sought to determine whether disease volume at prostate biopsy would correlate with genomic scores among men with favorable risk prostate cancer.

Materials And Methods: We identified all men with NCCN® (National Comprehensive Cancer Network®) very low and low risk disease who underwent Oncotype DX® prostate testing at our institution from 2013 to 2016. Disease volume was characterized as the percent of positive cores, the number of cores with greater than 50% involvement, the largest involvement of any single core and prostate specific antigen density.

Impact of 5α-Reductase Inhibitors on Disease Reclassification among Men on Active Surveillance for Localized Prostate Cancer with Favorable Features.

Purpose: We determined the effect of 5α-reductase inhibitors on disease reclassification in men with prostate cancer optimally selected for active surveillance.

Materials And Methods: In this retrospective review we identified 635 patients on active surveillance between 2002 and 2015. Patients with favorable cancer features on repeat biopsy, defined as absent Gleason upgrading, were included in the cohort.

Prognostic Significance of a Negative Confirmatory Biopsy on Reclassification Among Men on Active Surveillance.

Objective: To examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS).

Materials And Methods: Men with grade groups 1 and 2 disease on AS between 2002 and 2015 were identified who received a confirmatory biopsy within 1 year of diagnosis and ≥3 biopsies overall. The primary outcomes were pathologic reclassification by grade (any increase in primary Gleason pattern or Gleason score) or volume (>33% of sampled cores involved or increase in the number of cores with >50% involvement).

Intermediate-Term Outcomes for Men with Very Low/Low and Intermediate/High Risk Prostate Cancer Managed by Active Surveillance.

Purpose: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance.

Materials And Methods: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.

Surgical Salvage of Thermal Ablation Failures for Renal Cell Carcinoma.

Purpose: Cryoablation and radio frequency ablation are attractive modalities for small renal masses in patients with substantial comorbidities. However, salvage extirpative therapy for local recurrence after thermal ablation can be challenging due to associated perinephric fibrosis.

Materials And Methods: Patients with thermal ablation refractory tumors requiring surgical salvage from 1997 to 2013 were identified and retrospectively reviewed.

A comparison of plasma and prostate lycopene in response to typical servings of tomato soup, sauce or juice in men before prostatectomy.

Tomato product consumption and estimated lycopene intake are hypothesised to reduce the risk of prostate cancer. To define the impact of typical servings of commercially available tomato products on resultant plasma and prostate lycopene concentrations, men scheduled to undergo prostatectomy (n 33) were randomised either to a lycopene-restricted control group ( < 5 mg lycopene/d) or to a tomato soup (2-2¾ cups prepared/d), tomato sauce (142-198 g/d or 5-7 ounces/d) or vegetable juice (325-488 ml/d or 11-16·5 fluid ounces/d) intervention providing 25-35 mg lycopene/d. Plasma and prostate carotenoid concentrations were measured by HPLC.

The use of bovine pericardium for complex urologic venous reconstruction.

Objective: To describe the use of bovine pericardium (BP) in several scenarios for venous patching and as a tubularized graft in urologic surgery.

Methods: BP was used as patch or tubularized graft in 7 patients between 2010 and 2013. Clinical scenarios and operative indications were reviewed.

Transrectal saturation technique may improve cancer detection as an initial prostate biopsy strategy in men with prostate-specific antigen <10 ng/ml.

Background: Using transrectal saturation prostate biopsy (SPBx) as an initial strategy remains a controversial topic.

Objective: To compare SPBx with extended prostate biopsy (EPBx) as an initial biopsy template in a large sequential cohort study.

Design, Setting, And Participants: We reviewed 438 men with initial SPBx and 3338 men who underwent initial EPBx between January 2002 and October 2011.

Upper and middle trunk brachial plexopathy after robotic prostatectomy.

We describe 3 patients who developed injury of upper and middle brachial plexus trunks during robotic-assisted prostatectomy, and review factors potentially associated with this type of injury. Three patients underwent robotic-assisted prostatectomy. Surgical exposure was facilitated by steep head-down tilt position.

The effect of sunitinib on primary renal cell carcinoma and facilitation of subsequent surgery.

Purpose: We investigated the effect of sunitinib on locally advanced primary renal carcinoma tumors and the ability to facilitate subsequent surgery.

Materials And Methods: Patients with an unresectable primary renal tumor, with or without distant metastases, received 50 mg sunitinib with continuous daily dosing in a phase II trial. Computerized tomography was performed every 12 weeks to determine surgical resectability.

Quality of lymphadenectomy is equivalent with robotic and open cystectomy using an extended template.

Purpose: Extended lymph node dissection for bladder cancer provides better staging, cancerous node removal and potentially survival. Minimally invasive techniques have been criticized about the ability to adequately perform extended lymph node dissection. We compared the extended lymph node dissection quality of robotic and open cystectomy by assessing node yield and positivity.

Presacral and retroperitoneal lymph node involvement in urothelial bladder cancer: results of a prospective mapping study.

Purpose: We evaluated the incidence of positive lymph nodes in the presacral and retroperitoneal regions in patients who underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer.

Materials And Methods: As part of a prospective mapping study, 143 patients underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 2006 and 2010. Lymph nodes from 6 separate regions were labeled, including bilateral pelvic and common iliac, presacral and retroperitoneal.

Utility of percent free prostate-specific antigen in repeat prostate biopsy.

Objectives: To assess the utility of the percent free prostate-specific antigen (%fPSA) for the prediction of prostate cancer in men undergoing repeat biopsy.

Methods: A retrospective review was performed of 1037 patients in an institutional review board-approved repeat prostate biopsy database. A total of 617 patients who underwent 683 biopsies had all their data available for analysis.

Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management.

Objective: To report changes in grade and stage between initial diagnostic and repeat biopsies or resection for urothelial carcinoma (UTUC) and investigate the consequences for endoscopic management. Ureteroscopic management of upper tract UTUC is an alternative to nephroureterectomy, which is less invasive and preserves renal function. However, concerns about potential understaging, inaccurate grading, incomplete resection, lack of effective tertiary chemoprevention, and need for ureteroscopic surveillance limits it appeal.

Neoadjuvant systemic therapy or early cystectomy? Single-center analysis of outcomes after therapy for patients with clinically localized micropapillary urothelial carcinoma of the bladder.

Objectives: To analyze the treatment outcomes of patients with micropapillary bladder cancer (MPBC). MPBC is a rare variant of urothelial carcinoma with aggressive clinical behavior. Radical cystectomy is considered the standard approach for treatment of patients with localized disease; however, the role of perioperative systemic therapy has been poorly defined.

Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy.

Background: The prevalence of chronic kidney disease (CKD) in patients with upper tract urothelial carcinoma (UTUC) is poorly defined, both before and after nephrouretectomy. Although multimodal treatment paradigms for UTUC are under-developed, this has important implications on patients' ability to receive cisplatin-based combination chemotherapy (CBCC).

Methods: Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula in 336 patients with UTUC, who were treated at the Cleveland Clinic by nephroureterectomy since 1992.