Evaluating Treatment Patterns and the Role of Neoadjuvant Chemotherapy in Plasmacytoid Urothelial Carcinoma: Insights from a Combined National and Institutional Series.

BACKGROUND: Plasmacytoid urothelial carcinoma (PUC) is a rare histologic subtype of urothelial carcinoma of the bladder (BC). Our objective was to characterize treatment patterns and outcomes of PUC in the NCDB and our recent institutional experience. METHODS: The NCDB was queried for localized PUC cases between 2004 and 2020. Patients with PUC from a single institution (Yale School of Medicine) were also incorporated from 2021 onwards to not double-count patients. The primary outcomes were overall survival and treatment trends. RESULTS: A total of 146 patients were included, 123 from NCDB and 23 from Yale. The median overall survival (mOS) was 28 [IQR 7.5, 50.3] months, 23 [IQR 8.4, 46.3] months for the NCDB patients, and 36 [IQR 4.3, 68.1] for the Yale patients. The mOS for patients receiving neoadjuvant chemotherapy (NAC) was 60.0 [28.0, 91.9] vs. 14.8 months [0, 34.3] for patients without NAC, p = 0.038, though the benefit was not preserved in a Cox proportional hazard analysis incorporating the clinical stage, receipt of NAC, and age. The peritoneum was the most common site of metastasis (78.3%), followed by the liver and bones. CONCLUSION: Our findings underscore the formidable challenge posed by PUC, emphasizing its limited response to current therapies. Despite higher pT0 rates with NAC, the OS benefit remains inconclusive, highlighting the need for more effective treatments.

Association of Crowd-Sourced Assessment of Technical Skills and Outcomes of Robotic-assisted Radical Prostatectomy.

OBJECTIVE: To investigate if use of the Crowd-Sourced Assessment of Technical Skills (CSATS) platform and video peer review with constructive feedback is associated with improvement in technical skill and patient outcomes for robotic-assisted laparoscopic prostatectomy (RALP). METHODS: Five fellowship-trained urologists voluntarily submitted RALP cases for CSATS Global Evaluative Assessment of Robotic Skills (GEARS) scoring and expert narrative review between April 15, 2022-April 30, 2023. Surgeon-selected and randomly selected cases were reviewed. Surgeons underwent local peer review of videos with constructive feedback. Change in GEARS scores and frequency of postoperative outcomes over the 12-month periods before and during the study were analyzed in logistic regression models. Bias was assessed with sensitivity analysis comparing surgeon-selected to randomly selected cases. RESULTS: GEARS scores for randomly selected vs surgeon-selected cases did not differ significantly. Overall GEARS score correlated positively with annual surgical RALP volume (r = 0.39, P = .003) and negatively with years in practice (r = -0.34, P = .01). After adjusting for confounders, there was no significant improvement in overall GEARS Score (0.01 ± 0.02/month, P = .48); but likelihood of sepsis (Odds Ratio 0.07, 95% CI 0.01-1.00, P = .05) and pelvic fluid collection (Odds Ratio 0.09, 95% CI 0.01-0.99, P = .049) were significantly decreased during the intervention period (n = 165) compared to the prior 12months (n = 144). No outcome increased in likelihood (P > .05). CONCLUSION: Integration of CSATS and local video peer review is associated with significant improvement in patient outcomes after RALP, despite no significant change in surgeons' GEARS scores. This is the first study demonstrating improvement in patient RALP outcomes after implementation of such a paradigm in practicing surgeons.

Agreement and Reliability of Patient-measured Postvoid Residual Bladder Volumes.

OBJECTIVE: To assess the reliability, agreement with provider measurement, and patient preferences regarding patient self-measurement of postvoid residual bladder volume (PVR). PVR measurement in the nonhealthcare setting is a valuable opportunity for remote monitoring of voiding dysfunction patients. We hypothesized that patient self-measurement of PVR using a smart-device portable ultrasound system with artificial intelligence would demonstrate high reliability, strong agreement with provider measurement, and be preferred over provider measurements. METHODS: Patients were enrolled during outpatient Urology visits. PVRs were measured in triplicate by providers using each of the following: an FDA-cleared (standard) bladder scanner, the portable ultrasound probe using ultrasound images (Butterfly US image mode), and the portable ultrasound probe using abstract images (Butterfly abstract mode). Subjects self-measured PVRs in triplicate using both imaging modes and reported their experiences via questionnaire. Reliability was assessed via intraclass correlation. Agreement between methods was assessed via Bland-Altman analyses using a clinically acceptable difference threshold of 50 mL. RESULTS: Fifty patients were enrolled. Intraclass correlations ranged from 0.95 to 0.98 for each method. 95% limits of agreement between standard bladder scanner and patient self-measurement were - 71.73 mL and 86.73 mL using Butterfly US image mode and - 93.84 mL and 112.52 mL using Butterfly abstract mode, respectively. Most patients preferred self-measurement over provider measurement (74% vs 26%, respectively). CONCLUSION: Patient self-measurement of PVR using smart-device integrated portable ultrasound probes is feasible, reliable, and preferred by patients. Limits of agreement between patient self-measurement and standard bladder scanner measurements exceeded our clinically acceptable difference threshold, though the inherent error of ultrasound-based bladder volume measurements should be considered. Longitudinal PVR assessments in nonhealthcare settings may facilitate remote monitoring of voiding dysfunction patients.

Implementation of a health system intervention to reduce time from presentation to surgical intervention for pediatric testicular torsion.

PURPOSE: Testicular salvage rates for torsion are time-dependent1. Door to detorsion time has been identified as an independent testicular survival factor2. We describe an initiative to reduce door to incision (DTI) time for pediatric testicular torsion. MATERIALS AND METHODS: An institutional multidisciplinary quality improvement initiative with a primary outcome of reducing DTI time for pediatric testicular torsion was developed with multidisciplinary stakeholders. Several process and balancing measures were used as secondary outcomes to help interpret and verify the observed change in DTI time. Interventions were implemented in cycles. Initial interventions standardized assessment of suspected torsion by Emergency Medicine utilizing a validated scoring system. A threshold Testicular Workup for Ischemia and Suspected Torsion (TWIST) score led to parallel notification of essential services for rapid assessment and case prioritization3. Subsequently, bedside ultrasound in the Emergency Department was implemented. Progress was tracked in a live dashboard and analyzed with X-mR process control charts and Nelson rules. These tools are used in quality improvement and process control to demonstrate the significance of changes as they are being implemented, prior to when traditional hypothesis testing would be able to do so. We aimed to increase the proportion of cases with DTI times under 4 h from 64% to >90% within one year. RESULTS: We observed 22 torsion cases prior to and 62 following initial implementation. The percentage of cases with DTI times under 4 h improved from 64% to 95%. At week 29, a shift identified a significant change on the X chart, with reduction in mean DTI time from 221 to 147 min. At the same time, a shift on the mR chart identified reduction in patient-to-patient variation. Mean time from arrival to Urology evaluation decreased from 140 to 56 min, mean time from arrival to scrotal ultrasound decreased from 70 to 36 min, and mean time from scrotal ultrasound to surgical incision decreased from 128 to 80 min. These improvements highlight the two key successes of our project: application of the TWIST score and bedside ultrasound for rapid assessment of suspected testicular torsions, and parallel processing of the evaluation and management. CONCLUSIONS: Implementation of a protocol for pediatric testicular torsion increased the proportion of cases with DTI time <4 h to 95%, decreased mean DTI time, and decreased variation. Our protocol provides a model to improve timeliness of care in treating pediatric testicular torsion.

Association between sociodemographic factors and diagnosis of lethal prostate cancer in early life.

OBJECTIVE: A subset of patients are diagnosed with lethal prostate cancer (CaP) early in life before prostate-specific antigen (PSA) screening is typically initiated. To identify opportunities for improved detection, we evaluated patient sociodemographic factors associated with advanced vs. localized (CaP) diagnosis across the age spectrum. METHODS: We conducted a retrospective cohort study using the National Cancer Database, identifying patients diagnosed with CaP from 2004 to 2020. We compared characteristics of patients diagnosed at the advanced (cN1 or M1) versus localized (cT1-4N0M0) stage. Using multivariable logistic regression, we evaluated the associations among patient clinical and sociodemographic factors and advanced diagnosis, stratifying patients by age as ≤55 (before screening is recommended for most patients), 56 to 65, 66 to 75, and ≥76 years. RESULTS: We identified 977,722 patients who met the inclusion criteria. The mean age at diagnosis was 65.3 years and 50,663 (5.1%) had advanced disease. Overall, uninsured (OR = 3.20, 95% CI 3.03-3.78) and Medicaid-insured (OR 2.58, 95% CI 2.48-2.69) vs. privately insured status was associated with higher odds of diagnosis with advanced disease and this effect was more pronounced for younger patients. Among patients ≤55 years, uninsured (OR 4.14, 95% CI 3.69-4.65) and Medicaid-insured (OR 3.39, 95% CI 3.10-3.72) vs. privately insured patients were associated with higher odds of advanced cancer at diagnosis. Similarly, residence in the lowest vs. highest income quartile was associated with increased odds of advanced CaP in patients ≤55 years (OR 1.15, 95% CI 1.02-1.30). Black vs. White race was associated with increased odds of advanced CaP at diagnosis later in life (OR 1.17, 95% CI 1.09-1.25); however, race was not significantly associated with advanced stage CaP in those ≤55 years (P = 0.635). CONCLUSIONS: Sociodemographic disparities in diagnosis at advanced stages of CaP were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early CaP screening based on patient health insurance.

Local Therapeutics for the Treatment of Oligo Metastatic Prostate Cancer.

PURPOSE OF REVIEW: Metastatic prostate cancer remains universally lethal. Although de-novo metastatic prostate cancer was historically managed with systemic therapy alone, local therapies are increasingly utilized in the early treatment of the disease, particularly in patients with oligometastatic prostate cancer (OMPC). OMPC represents an intermediate stage between clinically localized and widespread metastatic disease. Diseases classified within this stage present an opportunity for localized targeting of the disease prior to progression to widespread metastases. The purpose of this review is to discuss the contemporary and emerging local therapies for the treatment of OMPC. RECENT FINDINGS: To date, there are three utilized forms of local therapy for OMPC: cryoablation, radiation therapy, and cytoreductive prostatectomy. Cryoablation can be utilized for the total ablation of the prostate and has shown promising results in patients with OMPC either in combination with ADT or with ADT and systemic chemotherapy. Radiation therapy along with ADT has demonstrated improvement in progression-free survival. The STAMPEDE Arm G, PEACE-1, and the HORRAD clinical trials have investigated radiation therapy for mPCa compared to standard of care versus systemic therapy with varying results. Cytoreductive radical prostatectomy (CRP) in conjunction with ADT has also been proposed in the management of OPMC with promising results from case-control and retrospective studies. Currently there are larger controlled trials investigating CRP for OPMC including the SIMCAP, LoMP, TRoMbone, SWOG 1802, IP2-ATLANTA, g-RAMPP, and FUSCC-OMPCa trials. Given the novel nature of local treatments for OPMC, treatment selection is still controversial and requires long-term follow-up and randomized clinical trials to aid patient and clinician decision making.

DNA Packaging and Genomics of the Salmonella 9NA-Like Phages.

We present the genome sequences of Salmonella enterica tailed phages Sasha, Sergei, and Solent. These phages, along with Salmonella phages 9NA, FSL_SP-062, and FSL_SP-069 and the more distantly related Proteus phage PmiS-Isfahan, have similarly sized genomes of between 52 and 57 kbp in length that are largely syntenic. Their genomes also show substantial genome mosaicism relative to one another, which is common within tailed phage clusters. Their gene content ranges from 80 to 99 predicted genes, of which 40 are common to all seven and form the core genome, which includes all identifiable virion assembly and DNA replication genes. The total number of gene types (pangenome) in the seven phages is 176, and 59 of these are unique to individual phages. Their core genomes are much more closely related to one another than to the genome of any other known phage, and they comprise a well-defined cluster within the family Siphoviridae To begin to characterize this group of phages in more experimental detail, we identified the genes that encode the major virion proteins and examined the DNA packaging of the prototypic member, phage 9NA. We show that it uses a pac site-directed headful packaging mechanism that results in virion chromosomes that are circularly permuted and about 13% terminally redundant. We also show that its packaging series initiates with double-stranded DNA cleavages that are scattered across a 170-bp region and that its headful measuring device has a precision of ±1.8%.IMPORTANCE The 9NA-like phages are clearly highly related to each other but are not closely related to any other known phage type. This work describes the genomes of three new 9NA-like phages and the results of experimental analysis of the proteome of the 9NA virion and DNA packaging into the 9NA phage head. There is increasing interest in the biology of phages because of their potential for use as antibacterial agents and for their ecological roles in bacterial communities. 9NA-like phages that infect two bacterial genera have been identified to date, and related phages infecting additional Gram-negative bacterial hosts are likely to be found in the future. This work provides a foundation for the study of these phages, which will facilitate their study and potential use.