Clinical outcomes and patterns of population-based management of urachal carcinoma of the bladder: An analysis of the National Cancer Database.

BACKGROUND: Given the low incidence of urachal carcinoma of the bladder (UCB), there is limited published data from contemporary population-based cohorts. This study aimed to describe demographic, clinicopathological features, and survival outcomes of patients diagnosed with UCB. METHODS: The National Cancer Database (2004-2016) was queried for UCB patients. Descriptive analyses characterized demographics and clinicopathologic features. We assessed 5-year overall survival (OS) rates of the entire cohort and subgroups of localized/locally advanced and metastatic disease. We utilized Cox proportional hazards models to assess the association between covariates of interest and all-cause mortality and to examine the impact of surgical technique and chemotherapy. RESULTS: We identified 841 patients with UCB. The most common histologic subtype was non-mucinous adenocarcinoma (39.6%). Approximately 50% had ≥cT2 disease, and 14.3% were metastatic at diagnosis. Altogether, partial cystectomy (60%) was most performed, and lymph node dissection was performed in 377 patients (44.8%), with specific temporal increase in utilization over the study period (p < 0.001). Overall, median OS was 59 months, and 5-year OS was 49%. In patients with localized/locally advanced disease, we found no association between partial and radical cystectomy (Hazards ratio [HR] 1.75; 95% CI 0.72-4.3) as well as receipt of perioperative chemotherapy (HR 1.97, 95% CI 0.79-4.90) and outcomes. Lastly, receipt of systemic therapy was not associated with survival benefit (HR 0.785, 95% CI 0.37-1.65) in metastatic disease cohort. CONCLUSION: This large population-based cohort provides insight into the surgical management and systemic therapy, without clear evidence on the association of chemotherapy and survival in the perioperative and metastatic setting.

Utilization and outcomes of metastasectomy for patients with metastatic urothelial cancer: An analysis of the national cancer database.

BACKGROUND: Surgical resection of oligometastatic disease has been shown to be associated with an improved survival in other malignancies, though its role is not established in metastatic urothelial carcinoma (mUC). We sought to examine utilization trends of metastasectomy in mUC and associated outcomes using the NCDB database. METHODS: We queried the NCDB from 2004 to 2016 for patients with metastatic urothelial carcinoma who had undergone metastasectomy. The annual utilization trend of metastasectomy was evaluated by linear regression. We compared overall survival (OS) between propensity score matched patients who had undergone metastasectomy and those who had not using two-sided log-rank and Cox regression models. We also performed sensitivity analyses on subcohorts of mUC. RESULTS: The utilization rate of metastasectomy in mUC was 7% and did not change significantly over time. Patients who received metastasectomy on average were younger, had >cT3 disease, had radical surgery to the primary tumor, and received systemic therapy. After propensity score matching, metastasectomy was not associated with an OS benefit for mUC patients (HR, 0.94; 95% CI, 0.83 to 1.07; P=0.38). Stratified subgroup analysis based on systemic therapy, radical surgery to primary tumor, clinical N stage, and primary location of disease did not show an OS benefit of metastasectomy. CONCLUSION: Metastasectomy is uncommonly used, though utilization has persisted over more than a decade. Despite selection biases and residual confounding favoring patients undergoing metastasectomy, we found similar OS among these individuals and those who did not undergo metastasectomy.

Comprehensive Assessment of Health Needs of Young Minority Males Attending a Family Planning Clinic.

The objective of this study was to assess the overall health, including sexual and reproductive health (SRH) knowledge and needs, sexual behaviors, and testicular health practices among young minority males. Anonymous questionnaires were administered to 18- to 25-year-old males receiving services at health clinics in a large southwestern U.S. city. The survey was completed by 258 males with a mean age of 20.8 years. Most young males (67.1%) identified as African American, and 32.9% as Hispanic. Results suggest study participants lack SRH knowledge related to pregnancy and condom effectiveness, and engage in risky sexual behavior including not using birth control at their last sexual encounter. Although 21.6% of participants had a sexually transmitted infection (STI) in the past year, approximately 80% perceived their STI/HIV risk as very low or low. Respondents had low engagement and lack of knowledge of testicular health practices. The majority of respondents (71.1%) reported having been in a physical fight one or more times and 18.1% reported being victims of intimate partner violence. These data support a need for comprehensive health services for minority young males.

Solifenacin and Tamsulosin Combination Therapy Decreases Urine Nerve Growth Factor/Creatinine Levels in Men.

OBJECTIVE: To evaluate urinary nerve growth factor (NGF)/creatinine (Cr) levels from men with symptomatic lower urinary tract symptoms (LUTS) and measure the effect of combination therapy with solifenacin and tamsulosin. MATERIALS AND METHODS: From January 2012 to February 2014, all male patients referred for evaluation and management of LUTS were screened for enrollment. In all subjects, urinary NGF and Cr levels were measured and normalized to the urinary Cr concentrations (NGF/Cr). Uroflow, postvoid residual, and symptom questionnaires were measured at baseline, 4 weeks, 8 weeks, and 12 weeks after starting combination therapy with solifenacin 5 mg and tamsulosin 0.4 mg. The primary endpoint was urinary NGF and NGF/Cr change from baseline compared with week 12. RESULTS: Ten patients were recruited into the study. Peak urine flow at baseline 20.3 ± 2.5 ml/s and postvoid residual 45.3 ± 13.6 ml did not significantly change with 3 months of combination treatment 14.9 ± 1.8 ml/s and 58.5 ± 23.9 ml. However, urine NGF/Cr (pg/mg) levels were significantly reduced following treatment with levels of 39.7 ± 6.6 at baseline to 17.9 ± 5.1 at 3 months (P value <.05). The decrease in urine NGF/Cr levels correlated with significant decreases in patient reported outcomes. CONCLUSION: Male patients with LUTS had decreased urinary NGF/Cr levels after treatment with combination solifenacin and tamsulosin in this novel pilot study. This corresponded with improvement in patient reported outcomes.

The Use of HCG-Based Combination Therapy for Recovery of Spermatogenesis after Testosterone Use.

INTRODUCTION AND AIM: About 3 million men take testosterone in the United States with many reproductive-age men unaware of the negative impact of testosterone supplementation on fertility. Addressing this population, we provide an early report on the use of human chorionic gonadotropin (HCG)-based combination therapy in the treatment of a series of men with likely testosterone-related azoospermia or severe oligospermia. METHODS: We retrospectively reviewed charts from two tertiary care infertility clinics to identify men presenting with azoospermia or severe oligospermia (<1 million sperm/mL) while taking exogenous testosterone. All were noted to have been placed on combination therapy, which included 3,000 units HCG subcutaneously every other day supplemented with clomiphene citrate, tamoxifen, anastrozole, or recombinant follicle-stimulating hormone (or combination) according to physician preference. MAIN OUTCOME MEASURE: Clinical outcomes, including hormone values, semen analyses, and clinical pregnancies, were tracked. RESULTS: Forty-nine men were included in this case series. Return of spermatogenesis for azoospermic men or improved counts for men with severe oligospermia was documented in 47 men (95.9%), with one additional man (2.1%) having a documented pregnancy without follow-up semen analysis. The average time to return of spermatogenesis was 4.6 months with a mean first density of 22.6 million/mL. There was no significant difference in recovery by type of testosterone administered or supplemental therapy. No men stopped HCG or supplemental medications because of adverse events. CONCLUSIONS: We here provide an early report of the feasibility of using combination therapy with HCG and supplemental medications in treating men with testosterone-related infertility. Future discussion and studies are needed to further characterize this therapeutic approach and document the presumed improved tolerability and speed of recovery compared with unaided withdrawal of exogenous testosterone.

The association of urinary nerve growth factor levels with bladder outlet obstruction in women.

OBJECTIVES: Nerve growth factor (NGF) has been proposed as a urinary biomarker and previously shown to be elevated in male patients with bladder outlet obstruction (BOO) and other lower urinary tract symptoms. No published studies have examined NGF as a potential urinary biomarker in women with BOO. The aims of this prospective study were to evaluate NGF levels in urine from women with anatomic BOO resulting from pelvic organ prolapse (POP) and/or previous incontinence surgery and to measure the effect associated with surgical or conservative management. METHODS: From January to September 2012, all female patients referred for evaluation and management of BOO from POP or previous incontinence surgery were screened for enrollment. Inclusion criteria included elevated postvoid residual, valsalva voiding on urodynamics, or urinary peak flow (Qmax) of 12 mL/s or less. A control group of 10 asymptomatic age-matched female volunteers was also recruited. In all subjects, urinary NGF and creatinine (Cr) levels were measured and normalized to the urinary Cr concentrations (NGF/Cr). Urinary NGF levels were measured at 1 month and 3 months after either surgical correction or initiation of clean intermittent catheterization. RESULTS: A total of 10 female patients with anatomic BOO (mean [SD] age of 66.2 [3.88] years) and 10 female control subjects (mean [SD] age of 62 [7] years) were recruited. Nine patients had POP. Six patients had undergone a previous anti-incontinence procedure. Five patients had both POP and undergone a previous anti-incontinence procedure. The urinary NGF/Cr levels in the study patients with BOO (mean [SE] 20.8 [4.31] pg/mg) were significantly higher (P = 0.0001) than the levels in the age-matched control group (5.6 [0.65] pg/mg). After treatment, the urinary NGF/Cr level significantly decreased to 6.50 (0.57) pg/mg (P = 0.01) CONCLUSIONS: In this study, female patients with anatomic BOO resulting from POP and/or previous incontinence surgery had significantly higher urinary NGF/Cr levels when compared with age-matched controls. After treatment, the urinary NGF/Cr levels significantly decreased.

Individual lytic efficacy of recombinant tissue plasminogen activator in an in vitro human clot model: rate of "nonresponse".

OBJECTIVES: Recombinant tissue plasminogen activator (rt-PA) is a lytic medication widely used in the emergency department to treat acute thrombotic disorders such as ischemic stroke and myocardial infarction. It is known in the clinical use of this drug that it can be less effective in approximately 25% of individuals receiving such treatment. However, there are no data on the variation of lytic efficacy of rt-PA in decreasing individuals' clot size over time. In this study, in vitro lytic efficacy was determined by measuring the decrease in clot diameter after 30 minutes of drug exposure. The authors sought to explore whether there are individuals who do not respond to this lytic therapy and to estimate the rate of nonresponse. METHODS: Human whole blood clots were made from blood drawn from 22 adult volunteers. The only exclusion criterion was the use of aspirin within 72 hours of the blood draw. Blood clots were allowed to spontaneously form at room temperature and were then incubated at 37°C for 3 hours to ensure complete clot retraction. Sample clots from the same individuals were then exposed to human fresh-frozen plasma (hFFP) control or rt-PA in hFFP (rt-PA) at a concentration of 3.15 µg/mL. All clots were exposed at 37°C for 30 minutes, and clot diameter was measured as a function of time, using a microscopic imaging technique. The fractional clot loss (FCL), which is the percentage decrease in clot diameter at 30 minutes, was used as a measure of lytic efficacy. RESULTS: Means with standard deviation (SD) FCL values were 8.6% (±3.0%) for control and 20.6% (±9.3%) for rt-PA-treated clots. The mean (±SD) difference in FCL values was 12.0% (±8.8%) and was significant (p < 0.05, paired t-test). Five of the 22 subjects (23%) were "rt-PA nonresponders," in that their FCL (rt-PA) values fell within that of the FCL control values. CONCLUSIONS: Overall, rt-PA does not produce clot lysis in vitro in clots from a substantial minority of the population, likely due to individual variations in clot composition and structure.

Temperature affects thrombolytic efficacy using rt-PA and eptifibatide, an in vitro study.

The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf ), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature. Here, clot lysis during exposure to the combination of rt-PA and Epf is measured in an in vitro human clot model at hypothermic temperatures. The hypothesis is that lytic efficacy of rt-PA and Epf decreases with decreasing temperature. Whole blood clots from 31 volunteers were exposed to rt-PA (0.5 µg/mL) and Epf (0.63 µg/mL) in human fresh-frozen plasma (rt-PA+Epf ), rt-PA alone in plasma (rt-PA Alone), or to plasma alone (Control), at temperatures from 30°C to 37°C, for 30 minutes. Clot lysis was measured using a microscopic imaging technique; the mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. Temperature had a significant impact on FCL in clots exposed to rt-PA+Epf, with the FCL being lower at 30°C to 36°C than at 37°C. The FCL remained significantly higher for rt-PA+Epf­treated clots than Controls regardless of temperature, with the exception of measurements made at 30°C when no significant differences in the FCL were observed between groups. The use of hypothermia as a neuroprotectant may negatively impact the therapeutic benefit of thrombolytic agents.