Disparities in cause-specific mortality by race and sex among bladder cancer patients from the SEER database.

PURPOSE: Previous literature shows that more bladder cancer patients overall die from causes other than the primary malignancy. Given known disparities in bladder cancer outcomes by race and sex, we aimed to characterize differences in cause-specific mortality for bladder cancer patients by these demographics. METHODS: We identified 215,252 bladder cancer patients diagnosed with bladder cancer from 2000 to 2017 in the SEER 18 database. We calculated cumulative incidence of death from seven causes (bladder cancer, COPD, diabetes, heart disease, external, other cancer, other) to assess differences in cause-specific mortality between race and sex subgroups. We used multivariable Cox proportional hazards regression and Fine-Gray competing risk models to compare risk of bladder cancer-specific mortality between race and sex subgroups overall and stratified by cancer stage. RESULTS: 17% of patients died from bladder cancer (n = 36,923), 30% died from other causes (n = 65,076), and 53% were alive (n = 113,253). Among those who died, the most common cause of death was bladder cancer, followed by other cancer and diseases of the heart. All race-sex subgroups were more likely than white men to die from bladder cancer. Compared to white men, white women (HR: 1.20, 95% CI: 1.17-1.23) and Black women (HR: 1.57, 95% CI: 1.49-1.66) had a higher risk of dying from bladder cancer, overall and stratified by stage. CONCLUSION: Among bladder cancer patients, death from other causes especially other cancer and heart disease contributed a large proportion of mortality. We found differences in cause-specific mortality by race-sex subgroups, with Black women having a particularly high risk of dying from bladder cancer.

Risk factors for postoperative Clostridium difficile infection after radical cystectomy for bladder cancer: a NSQIP database analysis.

INTRODUCTION: Patients undergoing cystectomy for bladder cancer are at an increased risk for Clostridium difficile infection (CDI) due to prolonged antibiotics and underlying comorbidities. We aim to evaluate CDI risk factors in cystectomy patients. MATERIALS AND METHODS: Utilizing National Surgical Quality Improvement Program (NSQIP), patients undergoing cystectomy with diagnosis of bladder cancer between 2015-2017 were included. Baseline demographics including age, sex, comorbidities, and preoperative labs were collected. Univariate and multivariable logistic regression were used to evaluate risk factors for and complications of CDI during the index hospitalization. RESULTS: There were a total of 6,432 patients included in the analysis, with 6,242 (96%) and 190 (4%) in the non-CDI vs. CDI groups, respectively. Patients with a diagnosis of postoperative CDI were more likely to be female [4.09% vs. 2.71%, p = 0.001] and have lower preoperative albumin [3.78 g/dL (0.52) vs. 3.92 g/dL (0.48), p = 0.003]. Patients with a history of female sex (OR 1.46, p = 0.03), neobladder (OR 1.57, p = 0.01), and low preoperative albumin (OR 1.45, p = 0.04) were at the highest risk for development of CDI postoperatively. Patients with a diagnosis of CDI were more likely to experience readmission within 30 days (31.1% vs. 19.2%, p < 0.001). CONCLUSION: Utilizing the NSQIP database, we identified predictors for development of CDI in cystectomy patients. Female sex, continent diversion, and low preoperative albumin all significantly increased the rate of CDI. While our findings are retrospective, they are compelling enough to warrant further prospective investigation.

Pediatric Thoracolumbar Spinal Injuries in United States Trauma Centers.

OBJECTIVES: Injuries are the leading cause of morbidity and mortality in children ages 1 to 18 years. There are limited studies about pediatric thoracolumbar (TL) spinal injuries; the purpose of this study was to characterize TL spinal injuries among pediatric patients evaluated in US trauma centers. METHODS: This was a retrospective cohort study of the National Trauma Data Bank. Patients aged 1 to 18 years with a thoracic or lumbar spinal injury sustained by blunt trauma during calendar years 2011 through 2016 were included. Cervical spinal injuries, death before arrival, or penetrating trauma were excluded. The data was abstracted, and missing data was addressed by imputations. Data was analyzed using descriptive statistics and multinomial logistic regressions. RESULTS: A total of 20,062 patients were included in the study. Thoracolumbar spinal injuries were more commonly sustained by 16- to 17-year-olds (45.7%), boys (56.6%), and White (74.8%). The injuries were often from a motor vehicle collision (MVC) (55.2%) and resulted in a bone injury (82.3%). Mechanism of injury and age were significant in predicting injury type. A fall was more likely than MVC to result in disc injury (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.24-2.33), strain injury (OR, 1.18; 95% CI, 1.05-1.34), or cord injury (OR, 1.27; 95% CI, 1.12-1.45). Younger children were more likely than adolescents to present with disc injury (OR, 2.79; 95% CI, 1.75-4.45), cord injury (OR, 1.46; 95% CI, 1.18-1.81), or strain injury (OR, 1.37; 95% CI, 1.09-1.72). CONCLUSIONS: To our knowledge, this is the largest pediatric TL spinal study. Clinicians should consider TL spinal injuries when adolescents present after an MVC, and specifically, TL spinal cord injuries when young children present after a fall. Additionally, pediatric TL spinal injury prevention should highlight motor vehicle and fall safety.

T1 and T2 MR fingerprinting measurements of prostate cancer and prostatitis correlate with deep learning-derived estimates of epithelium, lumen, and stromal composition on corresponding whole mount histopathology.

OBJECTIVES: To explore the associations between T1 and T2 magnetic resonance fingerprinting (MRF) measurements and corresponding tissue compartment ratios (TCRs) on whole mount histopathology of prostate cancer (PCa) and prostatitis. MATERIALS AND METHODS: A retrospective, IRB-approved, HIPAA-compliant cohort consisting of 14 PCa patients who underwent 3 T multiparametric MRI along with T1 and T2 MRF maps prior to radical prostatectomy was used. Correspondences between whole mount specimens and MRI and MRF were manually established. Prostatitis, PCa, and normal peripheral zone (PZ) regions of interest (ROIs) on pathology were segmented for TCRs of epithelium, lumen, and stroma using two U-net deep learning models. Corresponding ROIs were mapped to T2-weighted MRI (T2w), apparent diffusion coefficient (ADC), and T1 and T2 MRF maps. Their correlations with TCRs were computed using Pearson's correlation coefficient (R). Statistically significant differences in means were assessed using one-way ANOVA. RESULTS: Statistically significant differences (p < 0.01) in means of TCRs and T1 and T2 MRF were observed between PCa, prostatitis, and normal PZ. A negative correlation was observed between T1 and T2 MRF and epithelium (R = - 0.38, - 0.44, p < 0.05) of PCa. T1 MRF was correlated in opposite directions with stroma of PCa and prostatitis (R = 0.35, - 0.44, p < 0.05). T2 MRF was positively correlated with lumen of PCa and prostatitis (R = 0.57, 0.46, p < 0.01). Mean T2 MRF showed significant differences (p < 0.01) between PCa and prostatitis across both transition zone (TZ) and PZ, while mean T1 MRF was significant (p = 0.02) in TZ. CONCLUSION: Significant associations between MRF (T1 in the TZ and T2 in the PZ) and tissue compartments on corresponding histopathology were observed. KEY POINTS: • Mean T2 MRF measurements and ADC within cancerous regions of interest dropped with increasing ISUP prognostic groups (IPG). • Mean T1 and T2 MRF measurements were significantly different (p < 0.001) across IPGs, prostatitis, and normal peripheral zone (NPZ). • T2 MRF showed stronger correlations in the peripheral zone, while T1 MRF showed stronger correlations in the transition zone with histopathology for prostate cancer.

Diagnostic Yield of Incremental Biopsy Cores and Second Lesion Sampling for In-Gantry MRI-Guided Prostate Biopsy.

BACKGROUND. In-gantry MRI-guided biopsy (MRGB) of the prostate has been shown to be more accurate than other targeted prostate biopsy methods. However, the optimal number of cores to obtain during in-gantry MRGB remains undetermined. OBJECTIVE. The purpose of this study was to assess the diagnostic yield of obtaining an incremental number of cores from the primary lesion and of second lesion sampling during in-gantry MRGB of the prostate. METHODS. This retrospective study included 128 men with 163 prostate lesions who underwent in-gantry MRGB between 2016 and 2019. The men had a total of 163 lesions sampled with two or more cores, 121 lesions sampled with three or more cores, and 52 lesions sampled with four or more cores. A total of 40 men underwent sampling of a second lesion. Upgrade on a given core was defined as a greater International Society of Urological Pathology (ISUP) grade group (GG) relative to the previously obtained cores. Clinically significant prostate cancer (csPCa) was defined as ISUP GG 2 or greater. RESULTS. The frequency of any upgrade was 12.9% (21/163) on core 2 versus 10.7% (13/121) on core 3 (p = .29 relative to core 2) and 1.9% (1/52) on core 4 (p = .03 relative to core 3). The frequency of upgrade to csPCa was 7.4% (12/163) on core 2 versus 4.1% (5/121) on core 3 (p = .13 relative to core 2) and 0% (0/52) on core 4 (p = .07 relative to core 3). The frequency of upgrade on core 2 was higher for anterior lesions (p < .001) and lesions with a higher PI-RADS score (p = .007); the frequency of upgrade on core 3 was higher for apical lesions (p = .01) and lesions with a higher PI-RADS score (p = .01). Sampling of a second lesion resulted in an upgrade in a single patient (2.5%; 1/40); both lesions were PI-RADS category 4 and showed csPCa. CONCLUSION. When performing in-gantry MRGB of the prostate, obtaining three cores from the primary lesion is warranted to optimize csPCa diagnosis. Obtaining a fourth core from the primary lesion or sampling a second lesion has very low yield in upgrading cancer diagnoses. CLINICAL IMPACT. To reduce patient discomfort and procedure times, operators may refrain from obtaining more than three cores or second lesion sampling.

Abdominal and vaginal pelvic support with concomitant hysterectomy for uterovaginal pelvic prolapse: a comparative systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: While approximately 225,000 pelvic organ prolapse (POP) surgeries are performed annually in the US, there is no consensus on the optimal route for pelvic support for the initial treatment of uterovaginal prolapse (UVP). Our objective is to compare the outcomes of abdominal sacrocolpopexy (ASC) to vaginal pelvic support (VPS) with either uterosacral ligament suspension (USLS) or sacrospinous ligament fixation (SSF) in combination with hysterectomy for treating apical prolapse. METHODS: A systematic search was performed through March 2021. Studies comparing ASC with VPS for treatment of UVP were included in the review. The primary outcome was the rate of overall anatomic prolapse failure per studies' definition. Secondary outcomes included evaluating isolated recurrent vaginal wall prolapse, postoperative POP-Q points, total vaginal length (TVL), and Pelvic Floor Distress Inventory (PFDI-20) scores. Random effect analyses were generated utilizing R 4.0.2. RESULTS: Out of 4225 total studies, 4 met our inclusion criteria, including 226 patients in the ASC group and 199 patients in the VPS group. ASC was not found to be associated with a higher rate of vaginal wall prolapse recurrence (OR = 0.6; 95% CI = 0.2-2.4; P = 0.33). There was no significant difference between groups for anterior or apical vaginal wall prolapse recurrence (P = 0.58 and P = 0.97, respectively). ASC was associated with significantly longer TVL (mean difference [MD]: 1.01; 95% CI = 0.33-1.70; P = 0.02) and better POP-Q Ba scores [MD = -0.23; 95% CI = -0.37; -0.10; P = 0.01]. CONCLUSIONS: ASC and vaginal pelvic support (either USLS or SSF) have comparable anatomical outcomes. However, weak evidence of a difference in TVL and Ba was found. The strength of the evidence in this study is based on the small number of observational studies. A large, randomized trial is highly warranted.

Testosterone therapy and risk of breast cancer development: a systematic review.

PURPOSE OF REVIEW: We aim to conduct a systematic review of the literature, document all reported cases of breast cancer development in cis men and female-to-male (FtM) transgender men undergoing testosterone replacement therapy (TRT), and determine if testosterone poses a substantial risk of breast cancer development and recurrence. RECENT FINDINGS: A systematic search through December 2019 was performed. Out of 1890, 15 studies were eligible for inclusion in the final analyses. In total, 22 patients have developed breast cancer while on testosterone treatment. Four cases were cis men, whereas 18 cases were FtM. Age ranged from 18 to 61 years. Testosterone treatment duration ranged from 5 weeks up to 25 years. SUMMARY: There is a relatively higher incidence of BCa in FtM on CSH therapy compared with cis men on TRT. Because of the small sample size of reported cases, we cannot delineate the exact relationship between testosterone therapy and BCa development. Additionally, we have limited data to suggest that TRT should or should not be contraindicated in cis men and FtM with a prior history of breast cancer.

Stromal derived factor-1 plasmid as a novel injection for treatment of stress urinary incontinence in a rat model.

INTRODUCTION AND HYPOTHESIS: SDF-1 chemokine enhances tissue regeneration through stem cell chemotaxis, neovascularization and neuronal regeneration. We hypothesized that non-viral delivery of human plasmids that express SDF-1 (pSDF-1) may represent a novel regenerative therapy for stress urinary incontinence (SUI). METHODS: Seventy-six female rats underwent vaginal distention (VD). They were then divided into four groups according to treatment: pSDF-1 (n = 42), sham (n = 30), PBS (n = 1) and luciferase-tagged pSDF-1 (n = 3). Immediately after VD, the pSDF-1 group underwent immediate periurethral injection of pSDF-1, and the sham group received a vehicle injection followed by leak point pressure (LPP) measurement at the 4th, 7th and 14th days. Urogenital tissues were collected for histology. H&E and trichrome slides were analyzed for vascularity and collagen/muscle components of the sphincter. For the luciferase-tagged pSDF-1 group, bioluminescence scans (BLIs) were obtained on the 3rd, 7th and 14th days following injections. Statistical analysis was conducted using ANOVA with post hoc LSD tests. The Mann-Whitney U test was employed to make pair-wise comparisons between the treated and sham groups. We used IBM SPSS, version 22, for statistical analyses. RESULTS: BLI showed high expression of luciferase-tagged pSDF-1 in the pelvic area over time. VD resulted in a decline of LPP at the 4th day in both groups. The pSDF1-treated group demonstrated accelerated recovery that was significantly higher than that of the sham-treated group at the 7th day (22.64 cmH2O versus 13.99 cmH2O, p < 0.001). Functional improvement persisted until the 14th day (30.51 cmH2O versus 24.11 cmH2O, p = 0.067). Vascularity density in the pSDF-1-treated group was higher than in the sham group at the 7th and 14th days (p < 0.05). The muscle density/sphincter area increased significantly from the 4th to 14th day only in the pSDF-1 group. CONCLUSIONS: Periurethral injection of pSDF-1 after simulated childbirth accelerated the recovery of continence and regeneration of the urethral sphincter in a rat SUI model. This intervention can potentially be translated to the treatment of post-partum urinary incontinence.

Gene expression in stress urinary incontinence: a systematic review.

INTRODUCTION: A contribution of genetic factors to the development of stress urinary incontinence (SUI) is broadly acknowledged. This study aimed to: (1) provide insight into the genetic pathogenesis of SUI by gathering and synthesizing the available data from studies evaluating differential gene expression in SUI patients and (2) identify possible novel therapeutic targets and leads. METHODS: A systematic literature search was conducted through September 2017 for the concepts of genetics and SUI. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in SUI were performed using GeneMANIA software. RESULTS: Of 3019 studies, 4 were included in the final analysis. A total of 13 genes were identified as being differentially expressed in SUI patients. Eleven genes were overexpressed: skin-derived antileukoproteinase (SKALP/elafin), collagen type XVII alpha 1 chain (COL17A1), plakophilin 1 (PKP1), keratin 16 (KRT16), decorin (DCN), biglycan (BGN), protein bicaudal D homolog 2 (BICD2), growth factor receptor-bound protein 2 (GRB2), signal transducer and activator of transcription 3 (STAT3), apolipoprotein E (APOE), and Golgi SNAP receptor complex member 1 (GOSR1), while two genes were underexpressed: fibromodulin (FMOD) and glucocerebrosidase (GBA). GeneMANIA revealed that these genes are involved in intermediate filament cytoskeleton and extracellular matrix organization. CONCLUSION: Many genes are involved in the pathogenesis of SUI. Furthermore, whole-genome studies are warranted to identify these genetic connections. This study lays the groundwork for future research and the development of novel therapies and SUI biomarkers in clinical practice.

Sacral neuromodulation treating chronic pelvic pain: a meta-analysis and systematic review of the literature.

INTRODUCTION AND HYPOTHESIS: Sacral neuromodulation (SNM) is gaining popularity as a treatment option for chronic pelvic pain (CPP). Our hypothesis is that SNM is effective in improving CPP. METHODS: A systematic search was conducted through September 2018. Peer-reviewed studies using pre- and postpain intensity scores were selected. The primary outcome was pain improvement on a 10-point visual analog scale (VAS) (adjusted or de novo) in patients with CPP. Secondary outcomes included comparing SNM approaches and etiologies and evaluating lower urinary tract symptoms (LUTS). RESULTS: Fourteen of 2175 studies, evaluating 210 patients, were eligible for further analysis. The overall VAS pain score improvement was significant [weighted mean difference (WMD) -4.34, 95% confidence interval (CI) = -5.22, to-3.64, p < 0.0001)]. Regarding SNM approach, both standard and caudal approaches had significant reduction in pain scores: WMD -4.32, CI 95% = -5.32, to -3.31 (p < 0.001) for the standard approach, compared with WMD -4.63, 95% CI = -6.57 to -2.69 (P < 0.001), for the caudal approach (p = 0.75). While significant improvement in pain was observed both in patients with and without interstitial cystitis/bladder pain syndrome (IC/BPS), the observed improvement was lower in patients with (WMD -4.13, CI 95% -5.36 to -2.90 versus without (WMD -5.72, CI 95% = -6.18, to-5.27) IC/BPS (p = 0.02). SNM was effective in treating voiding symptoms (frequency, urgency, nocturia) associated with IC/BPS (all p < 0.01). CONCLUSIONS: SNM is an effective therapy for CPP in both IC/BSP and non-IC/BSP patients, with better results in non-IC/BSP patients. Outcomes of the antegrade caudal approach were comparable with the standard retrograde approach.

Variability in Prices for Erectile Dysfunction Medications-Are All Pharmacies the Same?

BACKGROUND: Variability in prices of medications is a well-known phenomenon; however, this variability has not been quantified in the realm of erectile dysfunction (ED) medications. ED medications are ideal for this quantification, because they are often not covered by insurances; therefore, the cost is the most direct reflection of price variability among pharmacies as they affect the patients. AIM: To evaluate the variability in cash prices for phosphodiesterase type 5 inhibitors (PDEIs) for ED. We also evaluated whether certain types of pharmacies consistently offer better pricing than others, and whether there was any correlation with demographic factors. METHODS: 331 pharmacies were contacted within a 25-mile radius of our institution to obtain the cash price for 4 commonly used ED medications with prespecified doses. After exclusion, 323 pharmacies were categorized as chain, independent, wholesale, or hospital-associated. Cash prices for the specified medications were evaluated. In addition, we identified demographic and socioeconomic factors to determine if these had an impact on median drug pricing within each zip code. MAIN OUTCOME MEASURE: The main outcome was the cost for patients to fill each prescription. RESULTS: Independent pharmacies provided the lowest cost for 3 of 4 of the PDEIs. The largest price difference for 10 tablets of 100 mg sildenafil between all pharmacies was 38,000%. The median cost difference between independent pharmacies and chain pharmacies for sildenafil was >900%, and >1,100% for independent pharmacies vs hospital-associated pharmacies. Demographic and socioeconomic factors had no impact on the cost. CLINICAL IMPLICATIONS: Our goal is to promote patient counseling among practitioners and to empower patients to shop for the best prices for their medications. STRENGTH AND LIMITATIONS: A strength of the study is the large cohort that was surveyed; however, a weakness is that the large majority of the cohort was comprised of chain pharmacies. Mail pharmacies could not be evaluated as they required a valid prescription before offering prices. CONCLUSION: The drastic differences in cash prices for the PDEIs give us an insight into the variability and cost-inflation of medications in the United States. These patterns hold true for other essential medications as well, and improved transparency will allow patients to make informed decisions when choosing where to purchase their medications. It may also encourage certain pharmacies to provide medications at more affordable prices. Mishra K, Bukavina L, Mahran A, et al. Variability in prices for erectile dysfunction medications-Are all pharmacies the same? J Sex Med 2018;15:1785-1791.

Bladder irrigation after transurethral resection of superficial bladder cancer: a systematic review of the literature.

INTRODUCTION: The vast majority of bladder cancer is non-muscle invasive with transurethral resection (TURBT) as the gold standard for surgical treatment. There is a high recurrence of bladder cancer post surgery, which adds to the frustration in current urologic practice. Current standard of care to further reduce bladder cancer recurrence is instillation of intravesical chemotherapy (ICT), a practice that is not routinely followed. Several studies point to similar effects with normal saline or water irrigation alone. Our objective is to review the current available literature and provide practicing urologist with an alternative to ICT. MATERIALS AND METHODS: A systematic search was performed through December 2017. Peer reviewed studies, which evaluated recurrence free survival (RFS) after bladder irrigation with saline or sterile water (SW) post-TURBT were included. Outcomes were analyzed in three groups: ICT, saline and sterile water. RESULTS: Six studies out of 981, including 1515 patients, were eligible. There was no significant difference between ICT, saline and SW groups regarding to the median RFS at 1 year [ICT: 81%, IQR (77.70, -81.00), SW: 74%, IQR (63.3-74.9), saline: 76.7% IQR (76.0, 77.7), p = 0.21]. While saline irrigation showed the highest median RFS among the groups, there was no statistically significant difference between the three groups [ICT: 70%, IQR (66.25, 73.75), SW: 64.1%, IQR (63.05, 65.15), saline: 73%, IQR (66.85, 74.50), p = 0.49]. Adverse events were more frequent amongst patients in the ICT group in comparison to the saline or water groups. CONCLUSION: Saline and sterile water irrigation provide an alternative to ICT with equivalent recurrence rate and lower incidence of adverse events.

The effect of sacral neuromodulation on pregnancy: a systematic review.

INTRODUCTION AND HYPOTHESIS: To evaluate the effects of sacral neuromodulation (SNM) on pregnancy and the impact of delivery on SNM function. METHODS: A systematic search was conducted through January 2016. We selected studies including women who had SNM and a subsequent pregnancy. RESULTS: Out of 2,316, eight studies were included, comprising 22 patients (26 pregnancies). SNM indications were Fowler's syndrome in 11, urinary retention in 6, fecal incontinence in 1, fecal and urinary urgency in 1, overactive bladder in 1, intractable interstitial cystitis in 1, and myelodysplasia in 1. SNM stayed on in 8 pregnancies. In the remaining 18 pregnancies in which the device was deactivated, 7 had recurrent urinary tract infections, including 1 with pyelonephritis and 2 who requested reactivation owing to recurrent symptoms. Outcomes were reported in 25 pregnancies, 16 had Cesarean section (CS) and 9 had vaginal delivery, including 2 operative deliveries. Out of 25, two infants had pilonidal sinus and motor tic disorder (exhibited at the age of 2 years), both from the same mother. After delivery, SNM was functioning in 15 (60%), 4 required reprogramming, and 3 required replacement (1 had recurrence of fecal incontinence after her operative delivery with evidence of displaced leads and 1 patient reported decreased SNM effects after her two CS), and 3 decided to remove the device (2 out of 3 patients were free of symptoms after SNM deactivation and requested removal). CONCLUSION: Within the current limited evidence, the decision regarding SNM activation or deactivation should be individualized. A registry for those patients is recommended.

Trends in testosterone prescription amongst medical specialties: a 5-year CMS data analysis.

Testosterone Therapy (TTh) trends have changed as a result of clinical research and market forces over the past several years. Understanding the trends or preferences regarding testosterone prescriptions remains unknown. Our objective was to assess both regional and national trends in TTh prescriptions amongst medical specialties within the United States between 2013 and 2017. Publicly available data from the Center for Medicare and Medicaid Services (CMS) Part D Prescriber database with regards to TTh prescriptions across a 5-year span (January 1, 2013-December 31, 2017) were analyzed. TTh therapies were consolidated into four categories: Topical, Oral, Injection and Pellet. Statistical analysis utilizing R 4.0.2 was performed on the resulting data. Trends in prescription modality claim count and cost were plotted over the study period while statistical analysis evaluated associations between TTh modality and medical specialist. We found that Endocrinologists and Urologists prescribed topical testosterone more than all other specialties (60.4% and 53.5%, respectively), while Family and Internal medicine physicians were more likely to prescribe injections (59.82% and 50.69%, respectively). Oral and pellet testosterone were rarely prescribed across all specialties. In conclusion, the wide variation in modalities of testosterone prescriptions illustrates an opportunity for treatment guidelines to be streamlined across all specialists to improve patient outcomes.

Novel radiomic analysis on bi-parametric MRI for characterizing differences between MR non-visible and visible clinically significant prostate cancer.

Background: around one third of clinically significant prostate cancer (CsPCa) foci are reported to be MRI non-visible (MRI─). Objective: To quantify the differences between MR visible (MRI+) and MRI─ CsPCa using intra- and peri-lesional radiomic features on bi-parametric MRI (bpMRI). Methods: This retrospective and multi-institutional study comprised 164 patients with pre-biopsy 3T prostate multi-parametric MRI from 2014 to 2017. The MRI─ CsPCa referred to lesions with PI-RADS v2 score < 3 but ISUP grade group > 1. Three experienced radiologists were involved in annotating lesions and PI-RADS assignment. The validation set (Dv) comprised 52 patients from a single institution, the remaining 112 patients were used for training (Dt). 200 radiomic features were extracted from intra-lesional and peri-lesional regions on bpMRI.Logistic regression with least absolute shrinkage and selection operator (LASSO) and 10-fold cross-validation was applied on Dt to identify radiomic features associated with MRI─ and MRI+ CsPCa to generate corresponding risk scores RMRI─ and RMRI+. RbpMRI was further generated by integrating RMRI─ and RMRI+. Statistical significance was determined using the Wilcoxon signed-rank test. Results: Both intra-lesional and peri-lesional bpMRI Haralick and CoLlAGe radiomic features were significantly associated with MRI─ CsPCa (p < 0.05). Intra-lesional ADC Haralick and CoLlAGe radiomic features were significantly different among MRI─ and MRI+ CsPCa (p < 0.05). RbpMRI yielded the highest AUC of 0.82 (95 % CI 0.72-0.91) compared to AUCs of RMRI+ 0.76 (95 % CI 0.63-0.89), and PI-RADS 0.58 (95 % CI 0.50-0.72) on Dv. RbpMRI correctly reclassified 10 out of 14 MRI─ CsPCa on Dv. Conclusion: Our preliminary results demonstrated that both intra-lesional and peri-lesional bpMRI radiomic features were significantly associated with MRI─ CsPCa. These features could assist in CsPCa identification on bpMRI.

Characterization of Changes in Penile Microbiome Following Pediatric Circumcision.

BACKGROUND: While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome. OBJECTIVE: Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and energy metabolism. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We obtained the predictive functional attributes of the microbial communities between samples using Silva-Tax4Fun and the Greengenes-Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) approach. The predictive functioning of the microbial communities was determined by linearly combining the normalized taxonomic abundances into the precomputed association matrix of Kyoto Encyclopedia of Genes and Genomes orthology reference profiles. RESULTS AND LIMITATIONS: Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p < 0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p < 0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. As expected, enrichment in methyl-accepting chemotaxis protein, an integral membrane protein involved in directed motility of microbes to chemical cues and environment, occurred prior to circumcision, while the filamentous hemagglutinin pathway (a strong immunogenic protein) was depleted after circumcision CONCLUSIONS: Our results offer greater insight into the host-microbiota relationship of penile circumcision and may serve to lay the groundwork for future studies focused on drivers of inflammation, infection, and oncogenesis. PATIENT SUMMARY: Our study showed a significant reduction in bacteria and fungi after circumcision, particularly anaerobic bacteria, which are known to be potential inducers of inflammation and cancer. This is the first study of its kind showing the changes in microbiome after circumcision, and some of the changes that occur in healthy infants after circumcision that may explain the differences in cancer and inflammatory disorders in adulthood.

Delta radiomic patterns on serial bi-parametric MRI are associated with pathologic upgrading in prostate cancer patients on active surveillance: preliminary findings.

Objective: The aim of this study was to quantify radiomic changes in prostate cancer (PCa) progression on serial MRI among patients on active surveillance (AS) and evaluate their association with pathologic progression on biopsy. Methods: This retrospective study comprised N = 121 biopsy-proven PCa patients on AS at a single institution, of whom N = 50 at baseline conformed to the inclusion criteria. ISUP Gleason Grade Groups (GGG) were obtained from 12-core TRUS-guided systematic biopsies at baseline and follow-up. A biopsy upgrade (AS+) was defined as an increase in GGG (or in number of positive cores) and no upgrade (AS-) was defined when GGG remained the same during a median period of 18 months. Of N = 50 patients at baseline, N = 30 had MRI scans available at follow-up (median interval = 18 months) and were included for delta radiomic analysis. A total of 252 radiomic features were extracted from the PCa region of interest identified by board-certified radiologists on 3T bi-parametric MRI [T2-weighted (T2W) and apparent diffusion coefficient (ADC)]. Delta radiomic features were computed as the difference of radiomic feature between baseline and follow-up scans. The association of AS+ with age, prostate-specific antigen (PSA), Prostate Imaging Reporting and Data System (PIRADS v2.1) score, and tumor size was evaluated at baseline and follow-up. Various prediction models were built using random forest (RF) classifier within a threefold cross-validation framework leveraging baseline radiomics (Cbr), baseline radiomics + baseline clinical (Cbrbcl), delta radiomics (CΔr), delta radiomics + baseline clinical (CΔrbcl), and delta radiomics + delta clinical (CΔrΔcl). Results: An AUC of 0.64 ± 0.09 was obtained for Cbr, which increased to 0.70 ± 0.18 with the integration of clinical variables (Cbrbcl). CΔr yielded an AUC of 0.74 ± 0.15. Integrating delta radiomics with baseline clinical variables yielded an AUC of 0.77 ± 0.23. CΔrΔclresulted in the best AUC of 0.84 ± 0.20 (p < 0.05) among all combinations. Conclusion: Our preliminary findings suggest that delta radiomics were more strongly associated with upgrade events compared to PIRADS and other clinical variables. Delta radiomics on serial MRI in combination with changes in clinical variables (PSA and tumor volume) between baseline and follow-up showed the strongest association with biopsy upgrade in PCa patients on AS. Further independent multi-site validation of these preliminary findings is warranted.

Prostate Surface Distension and Tumor Texture Descriptors From Pre-Treatment MRI Are Associated With Biochemical Recurrence Following Radical Prostatectomy: Preliminary Findings.

Objective: To derive and evaluate the association of prostate shape distension descriptors from T2-weighted MRI (T2WI) with prostate cancer (PCa) biochemical recurrence (BCR) post-radical prostatectomy (RP) independently and in conjunction with texture radiomics of PCa. Methods: This retrospective study comprised 133 PCa patients from two institutions who underwent 3T-MRI prior to RP and were followed up with PSA measurements for ≥3 years. A 3D shape atlas-based approach was adopted to derive prostate shape distension descriptors from T2WI, and these descriptors were used to train a random forest classifier (CS ) to predict BCR. Texture radiomics was derived within PCa regions of interest from T2WI and ADC maps, and another machine learning classifier (CR ) was trained for BCR. An integrated classifier CS + R was then trained using predictions from CS and CR . These models were trained on D1 (N = 71, 27 BCR+) and evaluated on independent hold-out set D2 (N = 62, 12 BCR+). CS + R was compared against pre-RP, post-RP clinical variables, and extant nomograms for BCR-free survival (bFS) at 3 years. Results: CS + R resulted in a higher AUC (0.75) compared to CR (0.70, p = 0.04) and CS (0.69, p = 0.01) on D2 in predicting BCR. On univariable analysis, CS + R achieved a higher hazard ratio (2.89, 95% CI 0.35-12.81, p < 0.01) compared to other pre-RP clinical variables for bFS. CS + R , pathologic Gleason grade, extraprostatic extension, and positive surgical margins were associated with bFS (p < 0.05). CS + R resulted in a higher C-index (0.76 ± 0.06) compared to CAPRA (0.69 ± 0.09, p < 0.01) and Decipher risk (0.59 ± 0.06, p < 0.01); however, it was comparable to post-RP CAPRA-S (0.75 ± 0.02, p = 0.07). Conclusions: Radiomic shape descriptors quantifying prostate surface distension complement texture radiomics of prostate cancer on MRI and result in an improved association with biochemical recurrence post-radical prostatectomy.

Impact of Music on Postoperative Pain, Anxiety, and Narcotic Use After Robotic Prostatectomy: A Randomized Controlled Trial.

Background: Music is a safe and cost-effective intervention that can reduce postoperative pain and anxiety. We investigated the effects of music therapy on postoperative recovery in patients undergoing robotic-assisted laparoscopic prostatectomy (RALP). Methods: Subjects were males 18 years and older undergoing RALP at a single tertiary care institution. Patients were randomized to music or control groups. The music group received 30 minutes of music in the recovery area and on postoperative day (POD) 1, while the control group was not provided postoperative music. Inpatient narcotic use (morphine milligram equivalent, or MME) and outpatient narcotic use were measured, and the State-Trait Anxiety Inventory (STAI) survey was completed on POD 1 and POD 7 by an inpatient advanced practitioner (AP). T-test and Chi-square were used to compare the groups. Linear regression was used to adjust for age, blood loss, and inpatient MME. Results: A total of 40 patients were prospectively recruited. There was no statistically significant difference in the hourly MME (2.06 [0.71-3.17] vs. 1.55 [0.83-3.37]) or total MME (49.52 [17-76] vs. 37.25 [20-69]) used in the music vs. non-music arms, respectively. Evaluation of STAI questionnaire revealed no overall differences in anxiety levels among the two groups on POD 1 or POD 7. After adjusting for age, blood loss, and inpatient MME use, patients assigned to the music intervention had a 26% reduction in post-hospitalization use. Conclusion: Our prospective randomized study suggests that music can be an AP-driven adjunct to facilitate postoperative patient comfort and reduce narcotic use upon discharge in prostate cancer patients.