Updates on Management of Biochemical Recurrent Prostate Cancer.

Patients with biochemical recurrent prostate cancer (BCR) are a heterogeneous group, whereby a personalized approach to management is critical. Patients with high-risk features such as PSA doubling time (PSADT) ≤ 9-12 months warrant earlier imaging for metastasis detection and consideration for intensified therapy (beyond intermittent androgen deprivation alone) during this phase of BCR-only disease. The BCR phase represents a unique opportunity to impact disease survival and delay metastasis progression.

Expression-based subtypes define pathologic response to neoadjuvant immune-checkpoint inhibitors in muscle-invasive bladder cancer.

Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling.

Hormonal Intensification Should Start at the Low-risk Stage in Metastatic Prostate Cancer.

Unlabelled: The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has dramatically evolved. Monotherapy androgen deprivation therapy (ADT) with testosterone suppression alone is no longer the standard of care as multiple global phase 3 trials of different combinatorial strategies have been clinically and statistically successful and the combinations have been incorporated into guidelines on advanced prostate cancer. For appropriate patients, clinicians should consider combining ADT with docetaxel or an androgen receptor pathway inhibitor, or possibly with both.

First-in-human Intravesical Delivery of Pembrolizumab Identifies Immune Activation in Bladder Cancer Unresponsive to Bacillus Calmette-Guérin.

Background: Intravenous immune checkpoint inhibition is an effective anticancer strategy for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) but may be associated with greater systemic toxicity compared with localized therapies.

Objective: We assessed the safety and antitumor activity of intravesical pembrolizumab combined with BCG.

Design, Setting, And Participants: A 3 + 3 phase 1 trial of pembrolizumab + BCG was conducted in patients with BCG-unresponsive NMIBC (NCT02808143).

Predictors of Failed Same-Day Catheter Removal After Holmium Laser Enucleation of the Prostate.

Objective: To determine factors associated with failure of same-day trial of void (SDTOV) following holmium laser enucleation of the prostate (HoLEP).

Background: HoLEP is increasingly utilized for patients with benign prostatic hyperplasia. Advancements in technology have improved operative efficiency and hemostasis making same-day, catheter-free discharge possible.

Role of Chromatin Modifying Complexes and Therapeutic Opportunities in Bladder Cancer.

Background: Chromatin modifying enzymes, mainly through post translational modifications, regulate chromatin architecture and by extension the underlying transcriptional kinetics in normal and malignant cells. Muscle invasive bladder cancer (MIBC) has a high frequency of alterations in chromatin modifiers, with 76% of tumors exhibiting mutation in at least one chromatin modifying enzyme [1]. Additionally, clonal expansion of cells with inactivating mutations in chromatin modifiers has been identified in the normal urothelium, pointing to a currently unknown role of these proteins in normal bladder homeostasis.

The Northwestern University Novel Urology Residency Curriculum: Updated Outcomes from a 13-Year Experience with Flexible Residency Training and Electives.

Introduction: We evaluated educational outcomes and satisfaction following institution of a novel, flexible and urology-driven resident curriculum.

Methods: A new urology resident curriculum was instituted at Northwestern University in 2006. Rotation schedules and resident electives were recorded annually.

Revisiting One-Stage Urethroplasties for Distal Urethral Strictures.

Background: Reconstructive approaches for distal urethral strictures range from simple meatotomy to utilizing grafts or flaps depending on the etiology, length and location. We describe a contemporary cohort of distal urethral strictures and report a surgical technique termed distal one-stage urethroplasty developed to address the majority of distal urethral strictures encountered.

Methods: Thirty-four patients were included.

Narrative review of penile distal urethroplasties and suggestions for optimizing outcomes.

Distal urethral strictures can be a challenging entity for urologists. Endoscopic maneuvers such as optical internal urethrotomies or dilations are even less successful than in other urethral locations and the repeated trauma will increase the scarring which advocates for a urethroplasty as primary option for patient management. Success rates of distal urethroplasties have been lower than those for other urethral strictures due to the anatomy of the distal urethra with a very thin corpus spongiosum associated with decreased mucosal blood supply.

Survival by T Stage for Patients with Localized Bladder Cancer: Implications for Future Screening Trials.

Background: There is insufficient data to recommend screening for bladder cancer (BC). For future BC screening trials, it is important to understand how and if tumor (T) stage can act as a surrogate outcome marker for overall (OS) and cancer-specific (CSS) survival.

Objective: To characterize OS and CSS between primary tumor (T) stages in non-metastatic bladder cancer (BC) patients.

Algorithms to Enhance Empiric Antimicrobial Choice for Outpatients With Afebrile Complicated Cystitis Reflects Importance of Status of the Urinary Tract and Patient Place of Residence.

Objective: To determine predictive factors for antimicrobial resistance patterns and to develop an antimicrobial treatment algorithm for afebrile outpatients presenting with complicated cystitis.

Materials And Methods: We performed a retrospective, single-center, cross-sectional study of 2,891 outpatients with a diagnosed afebrile complicated cystitis from 2012 to 2018. For patients with confirmed urinary tract infection and antimicrobial sensitivities, univariate analyses and multivariable regression models were used to determine odds ratios for predicting resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, nitrofurantoin, first-generation cephalosporin, and third-generation cephalosporin for the 2012-2016 data.

Anti-TNF agents and potential effects on male fertility: are men being counseled?

Background: Adult men with autoimmune conditions are commonly prescribed anti-tumor necrosis factor (anti-TNF) agents; however, there is a paucity of quality evidence as to their effect on male fertility (e.g. semen parameters and sperm quality).

Mutation signatures to Pan-Cancer Atlas: Investigation of the genomic landscape of muscle-invasive bladder cancer.

The Cancer Genome Atlas (TCGA) for bladder cancer was published in 2014 with updated annotation of over 400 patients with muscle-invasive bladder cancer (MIBC) in 2017. This tremendous work established the foundation of the genomic landscape of MIBC. The next steps to utilize information from The Cancer Genome Atlas is to (1) identify the causes of mutation, (2) determine the significant differences and sources of heterogeneity, and (3) apply these tools toward patient care.

Genomic and Therapeutic Landscape of Non-muscle-invasive Bladder Cancer.

Non-muscle-invasive bladder cancer (NMIBC) is heterogeneous, but current diagnostic and treatment strategies rely primarily on clinical parameters, lacking individualization to tumor and host genetics and biology. The heterogeneity of NMIBCs is derived from mutations, mutation signatures, chromosomal loss, and disruption of molecular pathways, which ultimately affects tumor progression, recurrence, and responsiveness to intravesical and systemic chemotherapy. Although research is still underway, advances in sequencing technology, insight into differential bacillus Calmette-Guérin responses, and new investigational treatment targets will soon offer clinicians new, precision-based tools to risk stratify and determine treatment regimens for future patients with bladder cancer.

A Review of Botulinum Toxin A for the Treatment of Neurogenic Bladder.

Prior to FDA approval of intradetrusor botulinum toxin (BoTA) injections for the treatment of neurogenic bladder, patients' treatment options were limited to use of pharmacotherapies such as antimuscarinics, alpha blockers, and more recently beta agonists (some off-label) or invasive interventions including bladder augmentation and urinary diversion procedures. Herein, we provide a comprehensive literature review detailing the salient clinical literature that led to FDA approval of intradetrusor BoTA for neurogenic bladder. Patients with neurogenic detrusor overactivity and detrusor sphincter dyssynergia have been shown in randomized studies to benefit significantly from intradetrusor BoTA injection with regard to the following parameters: improved voided volume, improved bladder pressure and urodynamic parameters, reduced incidence of urinary tract infection, and improved quality of life.

Canine-assisted Therapy as an Adjunct Tool in the Care of the Surgical Patient: A Literature Review and Opportunity for Research.

The use of canine-assisted therapy (CAT) in healthcare is expanding and the purpose of this review is to highlight its potential use in the surgical patient. While CAT literature to date has detailed widespread benefits in blood pressure control and improving pain, anxiety, and stress, little research has been performed specifically in surgical patients who may benefit significantly from CAT interventions. Critical points highlighted herein are as follows: (1) Hypertension is common and significantly increases morbidity and mortality associated with elective surgery.

Urethral Reconstruction in Aging Male Patients.

Objective: To report stricture characteristics, complications, and treatment outcomes among elderly men undergoing urethral reconstruction.

Materials And Methods: A retrospective review of urethroplasty cases and outcomes by a single surgeon from 2007 to 2014 was performed. Men were stratified by decade of life at time of surgery (<50, 50-59, 60-69, ≥70 years).

Delayed Reconstruction of Bulbar Urethral Strictures is Associated with Multiple Interventions, Longer Strictures and More Complex Repairs.

Purpose: Prior to urethral reconstruction many patients with stricture undergo a variable period during which endoscopic treatments are performed for recurrent obstructive symptoms. We evaluated the association among urethroplasty delay, endoscopic treatments and subsequent reconstructive outcomes.

Materials And Methods: We reviewed the records of men who underwent primary bulbar urethroplasty from 2007 to 2014.

ADAM10-Mediated ICOS Ligand Shedding on B Cells Is Necessary for Proper T Cell ICOS Regulation and T Follicular Helper Responses.

The proper regulation of ICOS and ICOS ligand (ICOSL) has been shown to be essential for maintaining proper immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant Ab production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear.

Characteristics of Idiopathic Urethral Strictures: A Link to Remote Perineal Trauma?

Objective: To characterize the physical features and reconstructive outcomes of a series of idiopathic urethral strictures (IUS) in an effort to elucidate the nature of this common yet poorly understood entity.

Patients And Methods: We retrospectively reviewed our urethroplasty database to identify men undergoing initial urethral reconstruction from 2007 to 2014 at 1 of 3 hospitals (N = 514). Patients were stratified by stricture etiology, including IUS, acute trauma, iatrogenic, hypospadias, balanitis xerotica obliterans, and radiation.

Impaired immunological synapse in sperm associated antigen 6 (SPAG6) deficient mice.

Sperm associated antigen 6 (SPAG6), a component of the central apparatus of the "9 + 2" axoneme, plays a central role in ciliary and flagellar motility; but, its contribution to adaptive immunity and immune system development is completely unknown. While immune cells lack a cilium, the immunological synapse is a surrogate cilium as it utilizes the same machinery as ciliogenesis including the nucleation of microtubules at the centrosome. This prompted our hypothesis that SPAG6 critically regulates the formation and function of immunological synapses.