Adoption, Safety, and Retreatment Rates of Prostatic Urethral Lift for Benign Prostatic Enlargement.

PURPOSE: Novel minimally invasive therapies like the prostatic urethral lift are among the many endoscopic options for the treatment of benign prostatic enlargement and lower urinary tract symptoms (BPE/LUTS). To further understand the relative uptake, complications and retreatment rates of contemporary endoscopic procedures for BPE/LUTS across diverse practice types, we performed a retrospective study of inpatient and ambulatory surgery encounters in the Premier Healthcare database. MATERIALS AND METHODS: We included men who underwent endoscopic procedures for BPE/LUTS between 2000 and 2018. We determined the utilization of endoscopic therapies for BPE/LUTS, 30-day and 90-day readmission rates, and retreatment rate. Multivariable logistic regression was used to assess the association of procedure type with outcomes for the 3 most commonly performed procedures. RESULTS: We identified 175,150 men treated with endoscopic surgery for BPE/LUTS. The annual percent utilization of the prostatic urethral lift increased from <1% in 2014 to 10.4% in 2018. Compared to transurethral resection of the prostate and prostate photovaporization, prostatic urethral lift was associated with a lower odds of readmission at 30 (OR 0.58, p <0.01) and 90 (OR 0.55, p <0.01) days and a higher odds of retreatment within 2 years of followup (OR 1.78, p <0.01). CONCLUSIONS: Providers have rapidly adopted prostatic urethral lift which accounted for more than 1 in 10 endoscopic procedures captured for BPE/LUTS in 2018. Men treated with prostatic urethral lift are readmitted less within 30 and 90 days but are more likely to be retreated within 2 years of their index procedure as compared to men treated with transurethral resection of the prostate or prostate photovaporization.

Increasing Utilization of MRI Before Prostate Biopsy in Black and Non-Black Men: An Analysis of the SEER-Medicare Cohort.

OBJECTIVE. The potential for significant disparities exists in the setting of increased adoption of prostate MRI. We sought to assess temporal trends in the utilization of MRI before prostate biopsy in a nationally representative sample. MATERIALS AND METHODS. Using the SEER-Medicare linked database, we identified men undergoing prostate biopsy who had an MRI within 6 months of diagnosis of prostate cancer. Men were stratified according to whether they were biopsy naive or had undergone a prior negative prostate biopsy. RESULTS. We identified 82,483 men undergoing prostate biopsy in SEER-Medicare from 2008 to 2015 of whom 78,253 were biopsy naive and 4230 had a known prior negative biopsy. We found that the percentage of patients who received an MRI before biopsy has increased from 2008 to 2015 in biopsy-naive men (0.5-8.2%; p < .001), men with a prior negative biopsy (1.4-25.5%; p < .001), and overall (0.5-9.2%; p < .001). On multivariable modeling, the odds ratio (OR) of a patient undergoing an MRI before biopsy for Black men (OR, 0.4; 95% CI, 0.3-0.5; p < .001) was half that of White men, and the OR of MRI before biopsy in men from the Northeast (OR, 3.4; 95% CI, 2.8-4.3; p < .001) was more than three times that of men from the West. CONCLUSION. The steady overall increase in the utilization of MRI before prostate biopsy since 2008 has been associated with significant racial and regional disparities in utilization.

Impact of prebiopsy magnetic resonance imaging on biopsy and radical prostatectomy grade concordance.

BACKGROUND: Adoption of prostate magnetic resonance imaging (MRI) before biopsy is based on evidence demonstrating superior detection of clinically significant prostate cancer on biopsy. Whether this is due to the detection of otherwise occult higher grade cancers or preferential sampling of higher grade areas within an otherwise low-grade cancer is unknown. METHODS: To distinguish these two possibilities, this study examined the effect of prebiopsy MRI on the rate of pathologic upgrading and downgrading at prostatectomy in Surveillance, Epidemiology, and End Results-Medicare linked data from 2010 to 2015. Logistic regression was performed to assess the effect of MRI use on the Gleason grade change between biopsy and prostatectomy. RESULTS: Among biopsy-naive men, those who underwent prebiopsy MRI had higher odds of downgrading at prostatectomy (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.05-1.66). In contrast, the odds of upgrading were significantly lower for men who underwent prebiopsy MRI (OR, 0.78; 95% CI, 0.61-0.99). Limitations included a low overall rate of MRI-utilization prior to biopsy and an inability to distinguish between template, software-assisted and cognitive fusion biopsy. CONCLUSIONS: Prebiopsy MRI is associated with both oversampling of higher grade areas, which results in downgrading at prostatectomy, and the detection of otherwise occult higher grade lesions, which results in less upgrading at prostatectomy.

Celastrol induces unfolded protein response-dependent cell death in head and neck cancer.

The survival rate for patients with oral squamous cell carcinoma (OSCC) has not seen marked improvement in recent decades despite enhanced efforts in prevention and the introduction of novel therapies. We have reported that pharmacological exacerbation of the unfolded protein response (UPR) is an effective approach to killing OSCC cells. The UPR is executed via distinct signaling cascades whereby an initial attempt to restore folding homeostasis in the endoplasmic reticulum during stress is complemented by an apoptotic response if the defect cannot be resolved. To identify novel small molecules able to overwhelm the adaptive capacity of the UPR in OSCC cells, we engineered a complementary cell-based assay to screen a broad spectrum of chemical matter. Stably transfected CHO-K1 cells that individually report (luciferase) on the PERK/eIF2α/ATF4/CHOP (apoptotic) or the IRE1/XBP1 (adaptive) UPR pathways, were engineered [1]. The triterpenoids dihydrocelastrol and celastrol were identified as potent inducers of UPR signaling and cell death in a primary screen and confirmed in a panel of OSCC cells and other cancer cell lines. Biochemical and genetic assays using OSCC cells and modified murine embryonic fibroblasts demonstrated that intact PERK-eIF2-ATF4-CHOP signaling is required for pro-apoptotic UPR and OSCC death following celastrol treatment.

Urology Mythbusters: Does prevalence of vesicoureteral reflux in children vary by race?

In this edition of Mythbusters, we examine the premise that prevalence of vesicoureteral reflux (VUR) in children varies by race. Specifically, we consider whether there is evidence supporting the contention that VUR is more common in White children and less common in Black children. Statements regarding the lower prevalence of VUR in Black children are ubiquitous in both research papers and reviews. Many of the references cited in support of these statements do not actually support the existence of racial variation in VUR, due to uncontrolled single-arm study designs, highly selected samples at risk for bias, or simply not addressing VUR prevalence at all. There is a small group of studies which directly compared VUR prevalence among children undergoing cystography, and these studies have found VUR to be less common among Black children compared to White children. However, the results of such papers can only be considered in the context of a system in which systemic bias and racism may impact access and care delivery in profound ways. Given that race is a social construct that bears little relationship to shared genetic ancestry or underlying biological characteristics, these findings must be approached with extreme caution. The goals of pediatric urological care should be to confer equitable care to all young children regardless of race.

Short communication: A pilot study to determine safety and feasibility of a commercial enuresis alarm to detect voiding in infants.

Accurate measurement of post-void residual (PVR) volumes requires accurate determination of the timing of voiding, which is challenging in non-verbal patients. As a proof of principle, we sought to test the feasibility, safety and efficacy of using an enuresis alarm to indicate voiding in ten infants. Each infant was observed for 4 h with alarm in the diaper, and diapers checked every 15-30 min to confirm voiding. The alarm activated in 31 of 33 voids (93.9%). No adverse events occurred. Further work will investigate whether this approach may improve accuracy of PVR measurement.

Characterizing psychosocial services in a pediatric urology practice.

INTRODUCTION: Psychosocial needs, which encompass behavioral health and social determinants of health (SDOH), are important mediators of the patient experience and health outcomes. However, many practices have limited experience with systematically assessing the non-billable psychosocial services provided to patients and families. OBJECTIVE: To characterize the non-billable activities of three psychosocial providers in a pediatric urology practice at a freestanding children's hospital. STUDY DESIGN: Following Institutional Review Board approval, an adapted version of the Care Coordination Measurement Tool (CCMT) was used to collect data prospectively on non-billable activities performed by a psychologist, social worker (SW), and certified child life specialist (CCLS) in a pediatric urology department. Variables included activity type, time spent per activity, and outcomes affected. Demographic data included age, sex, race, state, zip code, insurance type, and language. RESULTS: From April to October 2022, 3096 activities were performed in support of psychosocial needs over 947 encounters for 527 patients. The median patient age was 9.2 years (IQR 4.8-12.4); 48.4 % were male. The psychosocial providers most commonly identified care coordination needs related to delivery of urologic care (73.4 %), mental/behavioral/developmental health (29.1 %), and referral and appointment management (19.9 %). The largest proportion of time was spent on providing direct psychosocial support (45.9 %), consisting of psychosocial assessments, education, and other behavioral health interventions. A large proportion of time was also spent on care coordination activities, namely logistics and navigation support (35.9 %). Relative time allocation across activities varied by provider type (p < 0.001); care coordination constituted 64.2 % of non-billable activities for the psychologist, 57.8 % for the SW, and 12.3 % for the CCLS. Activities were associated with treatment plan modification in 37.7 % (n = 357), outpatient coordination in 22.5 % (n = 213), and treatment plan adherence in 19.0 % (n = 180) of encounters. DISCUSSION: This study enhances our understanding of psychosocial needs of patients in a pediatric urology practice by assessing non-billable psychosocial services not otherwise captured in the clinical workflow. In addition to direct psychosocial support, care coordination activities constitute a large proportion of such services. These data provide valuable insight into the range of activities necessary for the provision of specialty pediatric medical care. CONCLUSION: Psychosocial providers in a pediatric urology practice perform many non-billable care coordination and psychosocial support activities. Characterizing these activities is important for beginning to understand patients' psychosocial needs and informing resource deployment.

Ureteropelvic Junction Obstruction/Hydronephrosis.

Congenital hydronephrosis can be classified and managed based on the Urinary Tract Dilation consensus scoring system. Ureteropelvic junction obstruction is one of the most common causes of hydronephrosis in the pediatric population. Although most cases can be managed conservatively with follow-up and serial imaging, some patients need surgical repair because of renal function deterioration, infections, or symptoms. Additional research to create predictive algorithms or develop noninvasive biomarkers for renal deterioration is necessary to better identify surgical candidates. The robotic-assisted approach for pyeloplasty is becoming increasingly widespread and associated with shorter hospital stay, high success rates, and low complication rates.

Accuracy of telemedicine for diagnosis and pre-operative assessment of pediatric penile conditions.

INTRODUCTION: Patients with penile conditions comprise a significant proportion of any pediatric urology practice, and physical examination is the mainstay of diagnosis for such conditions. While the rapid adoption of telemedicine (TM) facilitated access to pediatric urology care during the pandemic, the accuracy of TM-based diagnosis for pediatric penile anatomy and pathology has not been studied. Our aim was to characterize the diagnostic accuracy of TM-based evaluation of pediatric penile conditions by comparing diagnosis during the initial virtual visit (VV) with a subsequent in-person visit (IPV). We also sought to assess the agreement between scheduled and actual surgical procedure performed. METHODS: A single-institution prospective database of male patients less than 21 years of age who presented for evaluation of penile conditions between August 2020 and December 2021 was analyzed. Patients were included if they had an IPV with the same pediatric urologist within 12 months of the initial VV. Diagnostic concordance was based on a surgeon-reported survey of specific penile diagnoses, completed at both initial VV and follow-up IPV. Surgical concordance was assessed based on the proposed versus billed CPT code(s). RESULTS: Median age among 158 patients was 10.6 months. The most frequent VV diagnoses were penile adhesions (n = 37), phimosis (n = 26), "other" (n = 24), post-circumcision redundancy (n = 18), and buried penis (n = 14). Initial VV and subsequent IPV diagnoses were concordant in 40.5% (64/158); 40/158 (25%) had partial concordance (at least one diagnosis matched). There was no difference in age, race, ethnicity, median time between visits, or device type between patients with concordant vs. discordant diagnoses. Of 102 patients who underwent surgery, 44 had VV only while 58 had IPV prior to surgery. Concordance of scheduled versus actual penile surgery was 90.9% in those patients who only had a VV prior to surgery. Overall, surgery concordance was lower among those with hypospadias repairs vs. non-hypospadias surgery (79.4% vs. 92.6%, p = 0.05). CONCLUSION: Among pediatric patients being evaluated by TM for penile conditions, there was poor agreement between VV-based and IPV-based diagnoses. However, besides hypospadias repairs, agreement between planned and actual surgical procedures performed was high, suggesting that TM-based assessment is generally adequate for surgical planning in this population. These findings leave open the possibility that, among patients not scheduled for surgery or IPV, certain conditions might be misdiagnosed or missed entirely.

A multidisciplinary approach to optimize primary prostate cancer biobanking.

PURPOSE: Biobanking tissue of high quality and fidelity is imperative for cancer genomics research. Since it is a challenging process, we sought to develop a protocol that improves the fidelity and quantity of biobanked primary prostate cancer (CaP) tissue. MATERIALS AND METHODS: We conducted a pilot study evaluating pathologic concordance of biobanked tissue and the radical prostatectomy specimen using either standard protocol (SP) vs. next-generation protocol (NGP). RESULTS: There were no significant differences in clinical and pathologic characteristics (age, BMI, preoperative PSA, prostate weight, race, final prostatectomy Gleason score, or pathologic tumor and nodal stages) between the two protocol arms. Utilization of the NGP compared to the standard protocol resulted in a significantly higher rate of pathologic concordance between the biobanked and RP specimens (61.8% vs. 37.9%, P = 0.0231) as well as a nearly two-fold increase in the amount of biobanked tumor tissue (330 mm3 vs. 174 mm3, P < 0.001). When looking at relevant clinical and pathologic characteristics, NGP was associated with pathologic concordance on both univariate [OR 2.65 (95% CI 1.13-6.21), P = 0.025] and multivariate analysis [OR 3.11 (95% CI 1.09-8.88), P = 0.034]. CONCLUSIONS: Our study validates the NGP as a multidisciplinary approach for improving the fidelity and amount of biobanked primary CaP tissue for future studies. Given the challenges to banking tissue from primary CaP as tumors are often difficult to visualize grossly and are frequently multifocal, optimizing the fidelity and volume of biobanked tissue is an important step forward to improve the generalizability of genomic data as we move towards precision medicine.

Collision tumors revealed by prospectively assessing subtype-defining molecular alterations in 904 individual prostate cancer foci.

BACKGROUNDProstate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought to characterize the subtype-defining molecular alterations of primary prostate cancer across all tumor foci within radical prostatectomy (RP) specimens and determine the prevalence of collision tumors.METHODSFrom the Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 to 2014 and assessed ETS-related gene (ERG), serine peptidase inhibitor Kazal type 1 (SPINK1), phosphatase and tensin homolog (PTEN), and speckle type BTB/POZ protein (SPOP) molecular status. We utilized dual ERG/SPINK1 immunohistochemistry and fluorescence in situ hybridization to confirm ERG rearrangements and characterize PTEN deletion, as well as high-resolution melting curve analysis and Sanger sequencing to determine SPOP mutation status.RESULTSBased on index focus alone, ERG, SPINK1, PTEN, and SPOP alterations were identified in 47.5%, 10.8%, 14.3%, and 5.1% of RP specimens, respectively. In 233 multifocal RPs with ERG/SPINK1 status in all foci, 139 (59.7%) had discordant molecular alterations between foci. Collision tumors, as defined by discrepant ERG/SPINK1 status within a single focus, were identified in 29 (9.4%) RP specimens.CONCLUSIONInterfocal molecular heterogeneity was identified in about 60% of multifocal RP specimens, and collision tumors were present in about 10%. We present this phenomenon as a model for the intrafocal heterogeneity observed in previous studies and propose that future genomic studies screen for collision tumors to better characterize molecular heterogeneity.FUNDINGEarly Detection Research Network US National Cancer Institute (NCI) 5U01 CA111275-09, Center for Translational Pathology at Weill Cornell Medicine (WCM) Department of Pathology and Laboratory Medicine, US NCI (WCM SPORE in Prostate Cancer, P50CA211024-01), R37CA215040, Damon Runyon Cancer Research Foundation, US MetLife Foundation Family Clinical Investigator Award, Norwegian Cancer Society (grant 208197), and South-Eastern Norway Regional Health Authority (grant 2019016 and 2020063).

Robotic Radical Cystectomy in the Contemporary Management of Bladder Cancer.

"The robotic approach for radical cystectomy has become increasingly adopted by the urologic oncology community, as it has been shown to have equivalent oncologic outcomes with shorter hospital stay and fewer perioperative transfusions. Consensus guidelines from expert surgeons have been published to provide guidance on all aspects of how to implement the robotic approach in the urologic oncology clinic."

Tumor size and genomic risk in localized prostate cancer.

PURPOSE: Unlike many other cancers, measurement of primary prostate tumor size has no defined role in the management of localized prostate cancer. Here, we assess whether prostate tumor size is associated with aggressive tumor biology using biomarkers of genomic risk. MATERIALS AND METHODS: We abstracted or imputed tumor size from the primary pathology reports of prostate cancers incorporated in The Cancer Genome Atlas. We used transcriptomic data to estimate the Cell Cycle Progression Score (CCPS, Prolaris), the Genomic Classifier Score (GCS, Decipher) and the Genomic Prostate Score (GPS, OncotypeDx), SChLaP1 expression, and copy number alteration percentage (%CNA) as well as hallmark gene set enrichment analysis. RESULTS: Tumor size and gene expression data was available for 267 men. On multivariable regression adjusted for Gleason Grade Group and tumor purity, tumor size was independently associated with the calculated (c)GCS, cGPS, SChLaP1 expression, and %CNA (P< 0.05), but not cCCPS. Gene set enrichment analysis demonstrated that tumors <5 cc, when adjusting for Gleason grade group, were enriched for androgen response genes, while tumors >5 cc were enriched for MYC targets and genes associated with epithelial mesenchymal transition. CONCLUSIONS: Prostate tumor size is independently associated with established markers of genomic risk. This study nominates the size of a primary prostate cancer as candidate for inclusion in future novel risk scores seeking to quantify cancer aggressiveness.

Prognostic value of the SPOP mutant genomic subclass in prostate cancer.

BACKGROUND: Speckle-type POZ protein (SPOP) mutation defines one of the dominant prostate cancer genomic subtypes, yet the impact of this mutation on clinical prognosis is unknown. METHODS: We defined SPOP mutation status either by DNA sequencing or by transcriptional signature in a pooled retrospective multi-institutional cohort, the Decipher retrospective cohort, the Decipher Genomics Resource Information Database prospective cohort, and The Cancer Genome Atlas. Kaplan-Meier survival analysis and multivariable Cox models were used to assess the independent impact of SPOP mutation on survival, biochemical recurrence and time to metastasis. The Decipher retrospective cohort was also used to assess the impact of the addition of SPOP mutation status to a model predicting adverse pathology at prostatectomy which was then validated in the Decipher prospective cohort. RESULTS: A fixed-effect model incorporating results from multivariable Cox regression including 5,811 subjects demonstrated that SPOP mutation was associated with a lower rate of adverse pathology at radical prostatectomy (odds ratios 0.57, 95% confidence interval 0.34-0.93), independent of preoperative prostate-specific antigen, age, and pathologic Gleason score. SPOP was not associated with biochemical recurrence, metastasis-free survival, or cancer-specific survival independent of pathologic information. The addition of SPOP status to prognostic models reclassified a large proportion of patients with the mutation (55%) into a favorable risk group when used to predict adverse pathology. CONCLUSION: While the clinical utility of delineating any single molecular alteration in prostate cancer remains unclear, these results illustrates the importance of genomic subtypes in prostate cancer behavior and potential role in prognostic tools.

Disulfiram (Antabuse) Activates ROS-Dependent ER Stress and Apoptosis in Oral Cavity Squamous Cell Carcinoma.

A paucity of advances in the development of novel therapeutic agents for squamous cell carcinomas of the head and neck, oral cavity (OSCC) and oropharynx, has stagnated disease free survival rates over the past two decades. Although immunotherapies targeted against checkpoint inhibitors such as PD-1 or CTLA-4 are just now entering the clinic for late stage disease with regularity the median improvement in overall survival is only about three months. There is an urgent unmet clinical need to identify new therapies that can be used alone or in combination with current approaches to increase survival by more than a few months. Activation of the apoptotic arm of the unfolded response (UPR) with small molecules and natural products has recently been demonstrated to be a productive approach in pre-clinical models of OSCC and several other cancers. The aim of current study was to perform a high throughput screen (HTS) with a diverse chemical library to identify compounds that could induce CHOP, a component of the apoptotic arm of the UPR. Disulfiram (DSF, also known as Antabuse) the well-known aversion therapy used to treat chronic alcoholism emerged as a hit that could generate reactive oxygen species, activate the UPR and apoptosis and reduce proliferation in OSCC cell cultures and xenografts. A panel of murine embryonic fibroblasts null for key UPR intermediates (e.g., Chop and Atf4) was resistant to DSF suggesting that an intact UPR is a key element of the mechanism regulating the antiproliferative effects of DSF.

Middle Cerebral Artery Occlusion Model of Stroke in Rodents: A Step-by-Step Approach.

Stroke is one of the leading causes of morbidity and mortality in developed countries and an immense amount of medical care resources are devoted to combat the poststroke debilitating consequences. The key to develop effective and clinically applicable treatment methodologies is a better understanding of the pathophysiology of the disease, including the root causes and targets for pharmacology. Developing these foundations requires the use of standard animal models that mimic the physicochemical process of the diseases that can reliably replicate results in order to test and fine-tune therapeutic modalities. Middle cerebral artery occlusion (MCAO), endothelin-1-induced ischemic stroke, photothrombosis, devascularization, embolization, and spontaneous infarction using hemorrhage are some examples of different animal models. Reliability of MCAO has been proved and due to the ability to induce reperfusion similar to tissue plasminogen activator (tPA) therapy, this model is widely used in preclinical studies. Here, we describe a detailed methodology on how to develop MCAO stroke in rodents using intra-arterial insertion of filament to occlude the middle cerebral artery. This approach allows for the study of a wide array of basic pathophysiology mechanisms, regenerative medicine and rehabilitation therapy.

Outcomes of Direct Vision Internal Urethrotomy for Bulbar Urethral Strictures: Technique Modification with High Dose Triamcinolone Injection.

Objective. To evaluate the recurrence rate of bulbar urethral strictures managed with cold knife direct vision internal urethrotomy and high dose corticosteroid injection. Methods. 28 patients with bulbar urethral strictures underwent direct vision internal urethrotomy with high dose triamcinolone injection into the periurethral tissue and were followed up for recurrence. Results. Our cohort had a mean age of 60 years and average stricture length of 1.85 cm, and 71% underwent multiple previous urethral stricture procedures with an average of 5.7 procedures each. Our technique modification of high dose corticosteroid injection had a recurrence rate of 29% at a mean follow-up of 20 months with a low rate of urinary tract infections. In patients who failed treatment, mean time to stricture recurrence was 7 months. Patients who were successfully treated had significantly better International Prostate Symptom Scores at 6, 9, and 12 months. There was no significant difference in maximum flow velocity on Uroflowmetry at last follow-up but there was significant difference in length of follow-up (p = 0.02). Conclusions. High dose corticosteroid injection at the time of direct vision internal urethrotomy is a safe and effective procedure to delay anatomical and symptomatic recurrence of bulbar urethral strictures, particularly in those who are poor candidates for urethroplasty.