A Pilot Study of the Effect of Transcutaneous Spinal Cord Stimulation on Micturition-Related Brain Activity and Lower Urinary Tract Symptoms After Stroke.

PURPOSE: Transcutaneous spinal cord stimulation (TSCS) is a novel neuromodulation modality developed to promote functional restoration in patients with neurological injury or disease. Previous pilot data suggest that lower urinary tract dysfunction (LUTD) due to stroke may be partially alleviated by TSCS. In this study, we examine the mechanism of this effect by evaluating bladder-related brain activity in patients before and after TSCS therapy and comparing it to healthy volunteers. MATERIALS AND METHODS: Patients who developed storage LUTD after a stroke and healthy volunteers without LUTD were recruited. Patients and healthy volunteers underwent simultaneous urodynamics and functional MRI. Patients then completed 24 biweekly sessions of TSCS and underwent another simultaneous urodynamics-functional MRI study. Clinical outcomes were assessed using validated questionnaires and voiding diary. RESULTS: Fifteen patients and 16 healthy volunteers completed the study. Following TSCS, patients exhibited increased blood-oxygen-level-dependent activity in areas including periaqueductal grey, the insula, the lateral prefrontal cortex, and motor cortex. Prior to TSCS therapy, healthy controls exhibited higher blood-oxygen-level-dependent activity in 17 regions, including multiple regions in the prefrontal cortex and basal ganglia. These differences were attenuated after TSCS with no frontal brain differences remaining between healthy volunteers and stroke participants who completed therapy. Neuroimaging changes were complemented by clinically significant improvements in questionnaire scores and voiding diary parameters. CONCLUSIONS: TSCS therapy modulated bladder-related brain activity, reducing differences between healthy volunteers and stroke patients with LUTD. These changes, alongside improved clinical outcomes, suggest TSCS as a promising approach for LUTD management.

Health Care Economic Burden of Treatment and Rehabilitation for Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

PURPOSE: The clinical, social, and economic impacts of neurogenic lower urinary tract dysfunction (NLUTD) on individuals and health care systems are thought to be immense, yet the true costs of care are unknown. The aims of this study are to illuminate the global costs related to the current state of care for NLUTD. MATERIALS AND METHODS: A systematic review of the literature was performed using MEDLINE, the National Health Service Economic Evaluation Database, and the Cochrane Specialized Urology and Incontinence Registers. Studies reporting the health care costs of NLUTD were identified. All steps of the review were performed by 2 independent reviewers. Costs were converted to 2022 U.S. dollars and reported for different categories of services. RESULTS: A total of 13 studies were included in the final review (12 from high-income economy, and 1 from an upper-middle-income economy). Routine maintenance care varied notably across studies in terms of included services. Annual supportive costs ranged from $2,039.69 to $12,219.07 with 1 study estimating lifetime costs of $112,774 when complications were considered. There were limited data on the costs of care from the patient's perspective. However, catheters and absorbent aids were estimated to be among the costliest categories of expenditure during routine care. More invasive and reconstructive treatments were associated with significant costs, ranging between $18,057 and $55,873. CONCLUSIONS: NLUTD incurs a variety of health care expenditures ranging from incontinence supplies to hospitalizations for management of complications and leads to a significant burden for health care systems over the patient's lifetime. Approaches to NLUTD that focus on functional rehabilitation and restoration, rather than on management of complications, may prove to be a less costly and more effective alternative.

The Impact of Radical Cystectomy and Urinary Diversion on Suicidal Death in Patients With Bladder Cancer.

PURPOSE: Compared to the general population, suicide is more common in the elderly and in patients with cancer. We sought to examine the incidence of suicide in patients with bladder cancer and evaluate the impact of radical cystectomy in this high-risk population. METHODS: Patients diagnosed with urothelial carcinoma from 1988 to 2010 were identified in the Survey, Epidemiology, and End Results (SEER) database. Contingency tables of suicide rates and standardized mortality ratios (SMRs) and 95% confidence intervals were calculated. Multivariable logistic regression models were performed to generate odds ratios (ORs) for the identification of factors associated with suicide in this population. RESULTS: There were 439 suicides among patients with bladder cancer observed for 1,178,000 person-years (Standard Morbidity Ratio [SMR] = 2.71). All demographic variables analyzed had a higher SMR for suicide compared to the general population, in particular age ≥80 years (SMR = 3.12), unmarried status (SMR = 3.41), and white race (SMR = 2.60). The incidence of suicide was higher in the general population for patients who underwent radical cystectomy compared to those who did not (SMR = 3.54 vs SMR = 2.66). On multivariate analysis, the strongest predictors of suicide were male gender (vs female; OR = 6.63) and distant disease (vs localized; OR = 5.43). CONCLUSIONS: Clinicians should be aware of risk factors for suicide in patients diagnosed with bladder cancer, particularly older, white, unmarried patients with distant disease, and/or those who have undergone radical cystectomy. A multidisciplinary team-based approach, including wound ostomy care trained nursing staff and mental health care providers, may be essential to provide care required to decrease suicide rates in this at-risk population.

Factors associated with suicide in patients with genitourinary malignancies.

BACKGROUND: Approximately 70% of all suicides in patients aged >60 years are attributed to physical illness, with higher rates noted in patients with cancer. The purpose of the current study was to characterize suicide rates among patients with genitourinary cancers and identify factors associated with suicide in this specific cohort. METHODS: Patients with prostate, bladder, kidney, testis, and penile cancer were identified in the Surveillance, Epidemiology, and End Results database (1988-2010). Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated for each anatomic site. Multivariable logistic regression models generated odds ratios (ORs) for the identification of factors associated with suicide for each malignancy. RESULTS: There were 2268 suicides identified among 1,239,522 individuals with genitourinary malignancies observed for 7,307,377 person-years. The SMRs for patients with cancer were 1.37 for prostate cancer (95% CI, 0.99-1.86), 2.71 for bladder cancer (95% CI, 2.02-3.62), 1.86 for kidney cancer (95% CI, 1.32-2.62), 1.23 for testis cancer (95% CI, 0.88-1.73), and 0.95 for penile cancer (95% CI, 0.65-1.35). On multivariable analysis, male sex was found to be associated with odds of suicide among patients with bladder cancer (OR, 6.63) and kidney cancer (OR, 4.98). Increasing age was associated with suicide for patients with prostate, bladder, and testis cancer (OR range, 1.03-1.06). Distant disease was associated with suicide in patients with prostate, bladder, and kidney cancer (OR range, 2.82-5.43). Among patients with prostate, bladder, and kidney cancer, African American patients were less likely to commit suicide compared with white individuals (OR range, 0.26-0.46). CONCLUSIONS: Suicide in patients with genitourinary malignancies poses a public health dilemma, especially among men, the elderly, and those with aggressive disease. Clinicians should be aware of risk factors for suicide in these patients.

Spillover Effects of the Hospital Readmissions Reduction Program on Radical Cystectomy Readmissions.

INTRODUCTION AND OBJECTIVE: Readmission rates after radical cystectomy are among the highest of any surgery. The Hospital Readmissions Reduction Program (HRRP) penalizes hospitals with excess readmissions for certain targeted conditions, including total hip and knee arthroplasty. We examined whether changes made by hospitals in response to the HRRP had spillover effects on radical cystectomy readmissions. METHODS: We used a 20% sample of Medicare data to identify patients undergoing cystectomy from 2010 to 2014 and measured 30-day adjusted cystectomy readmission rates. To determine the effect of the HRRP, we calculated adjusted readmission rates following total hip or knee arthroplasty and stratified hospitals into quartiles (most improved, middle quartiles, least improved) based on their improvement in reducing those targeted readmissions. Multivariable logistic regression was used to identify factors associated with spillover effects from the targeted joint surgery to cystectomy. RESULTS: We identified 2,394 patients undergoing radical cystectomy. Of these, 606 were treated at hospitals in the "most improved" quartile and 522 in the "least improved." Patients undergoing cystectomy were similar in age, comorbidity, and SEC independent of hospital performance quartile. The readmission rate following cystectomy was 26% in the most improved quartile and 24% in the least improved. No spillover effect was identified between readmission reduction after major joint surgery and radical cystectomy (adjusted OR 0.90, p=0.42). CONCLUSIONS: Hospitals that succeeded in reducing readmissions following major joint surgery targeted by the HRRP did not have similar reductions in readmissions following radical cystectomy. This lack of spillover effect suggests that each surgical condition may require tailored interventions to prevent readmissions.

Analysis of Suicide Risk in Patients with Penile Cancer and Review of the Literature.

The treatment for penile cancer has been shown to cause harmful psychiatric symptoms as well as have detrimental effects on well-being. In the past several years, alternatives to total or partial penectomy have emerged, such as chemotherapy, radiation, penile sparing, and laser ablation therapies. A more specific breakdown for penile cancer is in order as the therapy has the potential for life changing surgery. We examined the Surveillance, Epidemiology, and End Results (SEER) database (1973-2013), comprising 28% of the United States population. International Classification of Diseases, Tenth revision codes C60.8-C60.9 and the International Classification of Diseases-Oncology codes 8010/2, 8010/3, 8051/2, 8051/3, 8052/2, 8052/3, 8070/2, 8070/3-8072/3, 8074/3, 8076/3, and 8083/3-8084/3 were used. Age, race, marital status, and clinicopathologic variables were studied. We used contingency tables of suicide rates; mid-P exact test was used for analysis. There were 13 suicides noted in 6155 patients with squamous cell carcinoma of the penis. All patients that committed suicide had undergone a surgical intervention. Certainly, penile cancer after treatment has a powerful effect on quality of life as increased depression and sexual anxiety have been documented in postoperative patients. This is in contrast to the observed suicide rate. Despite the reported negative psychological effects in patients with penile cancer, suicide rates are among the lowest of all urologic malignancies.

Characterization and outcomes of local treatment for primary bladder lymphoma: A population-based cohort analysis.

INTRODUCTION: Primary bladder lymphoma (PBL) is rare, representing 0.2% of extranodal lymphoma and less than 1% of all tumors originating in the bladder. Since the initial description of the disease, low-grade mucosa-associated lymphoid tissue (MALT) lymphoma has been reported as the most common subtype while high-grade disease was thought to represent only 20% of the reported cases. MATERIALS AND METHODS: One hundred and ninety five patients with PBL from the Surveillance, Epidemiology, and End Results (SEER) registry from 1998-2010 were reviewed. Tumors were classified as high or low grade based on histologic subtype of lymphoma based on revised European-American Lymphoma classification system. Socio-demographic and clinical variables were reported, as well as survival outcome analyses using the Kaplan-Meier method and log-rank test. Cox proportional hazard analysis was used to generate hazard ratios for risk factors associated with mortality. RESULTS: Eighty-three patients (42.6%) with low-grade and 112 patients (57.4%) with high-grade bladder lymphoma were studied. There were no differences between the low and high-grade groups for socio-demographic or clinical variables. Median overall survival or patients with low-grade disease was 38 months versus 15 months for patients with high-grade disease (p< 0.001). Analysis demonstrated worse survival outcomes for patients with high-grade disease compared to low-grade disease (p< 0.001). On multivariable analysis, increasing age and high-grade disease were associated with worse disease specific mortality (p< 0.001). CONCLUSION: Patient with high-grade primary bladder lymphoma had worse survival outcomes compared to those with low-grade disease. While transurethral resection provides tissue for diagnosis, immunotherapy/chemotherapy remains the mainstay of treatment for bladder lymphoma. Consolidation chemotherapy has been recommended in young patients not achieving complete remission with immunotherapy/chemotherapy.

Female, Black, and Unmarried Patients Are More Likely to Present With Metastatic Bladder Urothelial Carcinoma.

BACKGROUND: Although there are well-established risk factors for the diagnosis of bladder cancer, there is no consensus regarding risk factors for presentation of advanced or metastatic disease at diagnosis. The objective of this study was to identify the demographic and clinical factors associated with metastasis at diagnosis in patients with bladder urothelial carcinoma. PATIENTS AND METHODS: Patients diagnosed with bladder urothelial carcinoma from 2004 to 2010 were identified in the Surveillance, Epidemiology, and End Results (SEER) database (n = 108,417). The primary outcome was metastatic disease at the time of diagnosis. Demographic and socioeconomic variables were analyzed, and multivariable logistic regression models were performed to generate odds ratios (OR) for factors associated with metastasis at diagnosis. RESULTS: Of patients with bladder cancer, 3018 (2.8%) had metastasis at diagnosis and 105,399 (97.2%) had nonmetastatic disease. Patients with metastatic disease at diagnosis were more frequently female (29.6% vs. 23.6%, P < .001), black (9.4% vs. 5.0%, P < .001), and unmarried (44.1% vs. 32.5%, P < .001) compared to patients with nonmetastatic disease. On multivariable analysis, the following characteristics were confirmed to be independently associated with metastatic disease at diagnosis: female gender (vs. male, OR 1.21), black race (vs. white, OR 1.71), unmarried (vs. married, OR 1.46), unemployed (OR 1.02), and foreign-born status (OR 1.01). CONCLUSION: Female gender, black race, unmarried, unemployed, and foreign-born status are independently associated with metastasis at diagnosis for bladder urothelial carcinoma. All clinicians should be aware of these potential health care disparities in order to involve social services and other support mechanisms in efforts to improve early care.

Novel structural determinants on SIRP alpha that mediate binding to CD47.

Signal regulatory proteins (SIRP-alpha, -beta, and -gamma) are important regulators of several innate immune functions that include leukocyte migration. Membrane distal (D1) domains of SIRPalpha and SIRPgamma, but not SIRPbeta, mediate binding to a cellular ligand termed CD47. Because the extracellular domains of all SIRPs are highly homologous, we hypothesized that some of the 16 residues unique to SIRPalpha.D1 mediate binding to CD47. By site-directed mutagenesis, we determined that SIRPalpha binding to CD47 is independent of N-glycosylation. We also identified three residues critical for CD47 binding by exchanging residues on SIRPalpha with corresponding residues from SIRPbeta. Cumulative substitutions of the critical residues into SIRPbeta resulted in de novo binding of the mutant protein to CD47. Homology modeling of SIRPalpha.D1 revealed topological relationships among critical residues and allowed the identification of critical residues common to SIRPalpha and SIRPbeta. Mapping these critical residues onto the recently reported crystal structure of SIRPalpha.D1 revealed a novel region that is required for CD47 binding and is distinct and lateral to another putative CD47 binding site described on that crystal structure. The importance of this lateral region in mediating SIRPalpha.D1 binding to CD47 was confirmed by epitope mapping analyses of anti-SIRP Abs. These observations highlight a complex nature of the ligand binding requirements for SIRPalpha that appear to be dependent on two distinct but adjacent regions on the membrane distal Ig loop. A better understanding of the structural basis of SIRPalpha/CD47 interactions may provide insights into therapeutics targeting pathologic inflammation.