Urinary dysfunction in transgenic sickle cell mice: model of idiopathic overactive bladder syndrome.

Voiding abnormalities are common among the sickle cell disease (SCD) population, among which overactive bladder (OAB) syndrome is observed at rates as high as 39%. Although detrusor overactivity is the most common cause of OAB, its molecular pathophysiology is not well elucidated. The nitric oxide (NO) signaling pathway has been implicated in the regulation of lower genitourinary tract function. In the present study, we evaluated the role of the NO signaling pathway in voiding function of transgenic SCD mice compared with combined endothelial and neuronal NO synthase gene-deficient mice, both serving as models of NO deficiency. Mice underwent void spot assay and cystometry, and bladder and urethral specimens were studied using in vitro tissue myography. Both mouse models exhibited increased void volumes; increased nonvoiding and voiding contraction frequencies; decreased bladder compliance; increased detrusor smooth muscle contraction responses to electrical field stimulation, KCl, and carbachol; and increased urethral smooth muscle relaxation responses to sodium nitroprusside compared with WT mice. In conclusion, our comprehensive behavioral and functional study of the SCD mouse lower genitourinary tract, in correlation with that of the NO-deficient mouse, reveals NO effector actions in voiding function and suggests that NO signaling derangements are associated with an OAB phenotype. These findings may allow further study of molecular targets for the characterization and evaluation of OAB.

Potential Association of Weight-Based Gentamicin with Increased Acute Kidney Injury in Urologic Prosthetic Surgery.

BACKGROUND: Despite the known nephrotoxicity of gentamicin, in 2008 the American Urological Association recommended a weight-based gentamicin dose of 5 mg/kg for antimicrobial prophylaxis during urologic prosthetic surgery. AIM: To identify and characterize rates of acute kidney injury (AKI) in urologic prosthetic surgery, both before and after the implementation of weight-based gentamicin dosing. METHODS: We performed a single-institution retrospective study of patients receiving perioperative gentamicin during implant, revision, salvage, or explant of inflatable penile prostheses, malleable penile prostheses, or artificial urinary sphincters between the years 2000 and 2017. Patients were stratified into 2 groups, based on administration of either weight-based gentamicin (5 mg/kg or 2-3 mg/kg in cases of poor renal function) or standard-dose gentamicin (80 mg). Patient characteristics and perioperative outcomes were identified. Patients with available preoperative and postoperative (≤7 days) serum creatinine values were included. AKI was defined by Kidney Disease: Improving Global Outcomes criteria. Comparative analyses were performed between groups. MAIN OUTCOME MEASURE: Our primary outcome was incidence of AKI, with secondary outcomes including device infection rate and length of stay. RESULTS: Of the 415 urologic prosthetic surgeries performed during the study period, 124 met inclusion criteria with paired preoperative and postoperative serum creatinine values. 57 received weight-based gentamicin (median dose 5.06 mg/kg, interquartile range [IQR] 3.96-5.94) and 67 received standard-dose gentamicin (median dose 1.07 mg/kg, IQR 1.04-1.06), P < .001. There were no significant differences in preoperative renal function or comorbidities between groups; however, the weight-based group was older (median age 64.0 years, IQR 60.0-68.5) compared with the standard-dose group (median age 61.0 years, IQR 55.0-66.0), P = .01, and comprised fewer explant cases (1.8%, 1 of 57) than the standard-dose group (13.4%, 9 of 67), P = .02. The AKI rate was significantly higher in the weight-based group (15.8%, 9 of 57) compared with the standard-dose group (3.0%, 2 o67), P = .02. Device infection rate was similar between groups (5.3%, 3/56 vs 5.2%, 3 of 58), P = 1.00. CLINICAL IMPLICATIONS: Our data suggest weight-based perioperative gentamicin prophylaxis may be associated with an increased AKI risk, without noticeably improving infection rates. STRENGTH & LIMITATIONS: Strengths of our study include the Veterans Affairs population analyzed, as well as rigorous inclusion criteria that allowed for a sensitive assessment of postoperative renal function. Limitations include the retrospective design and small sample size. CONCLUSION: Weight-based gentamicin dosing may warrant closer perioperative monitoring of renal function, and merits larger investigations to further elucidate risks and benefits. Moore RH, Anele UA, Krzastek SC. Potential Association of Weight-Based Gentamicin with Increased Acute Kidney Injury in Urologic Prosthetic Surgery. J Sex Med 2019;16:137-144.

Robotic versus laparoscopic radical nephrectomy: a large multi-institutional analysis (ROSULA Collaborative Group).

OBJECTIVE: To compare the outcomes of robotic radical nephrectomy (RRN) to those of laparoscopic radical nephrectomy (LRN) for large renal masses. METHODS: This was a retrospective analysis of RRN and LRN cases performed for large (≥ cT2) renal masses from 2004 to 2017 and collected in the multi-institutional international database (ROSULA: RObotic SUrgery for LArge renal masses). Peri-operative, functional, and oncologic outcomes were compared between each approach. Descriptive analyses were performed and presented as medians with interquartile ranges. Inverse probability of treatment weighting-adjusted multivariable analyses were used to identify predictors of peri-operative complications. Kaplan-Meier analysis and Cox regression models were used to assess survival outcomes. RESULTS: A total of 941 patients (RRN = 404, LRN = 537) were identified. There was no difference in terms of gender, age, and clinical tumor size. Over the study period, RRN had an annual increase of 11.75% (95% CI [7.34, 17.01] p < 0.001) and LRN had an annual decline of 5.39% (95% CI [-6.94, -3.86] p < 0.001). Patients undergoing RRN had higher BMI (27.6 [IQR 24.8-31.1] vs. 26.5 [24.1-30.0] kg/m2, p < 0.01). Operative duration was longer for RRN (185.0 [150.0-237.2] vs. 126 [90.8-180.0] min, p < 0.001). Length of stay was shorter for RRN (3.0 [2.0-4.0] vs. 5.0 [4.0-7.0] days, p < 0.001). RRN cases presented more advanced disease (higher pathologic staging [pT3-4 52.5 vs. 24.2%, p < 0.001], histologic grade [high grade 49.3 vs. 30.4%, p < 0.001], and rate of nodal disease [pN1 5.4 vs. 1.9%, p < 0.01]). Surgical approach did not represent an independent risk factor for peri-operative complications (OR 1.81 95% CI [0.97-3.39], adjusted p = 0.2). The main study limitation is the retrospective design. CONCLUSIONS: This study represents the largest known multi-center comparison between RRN and LRN. The two procedures seem to offer similar peri-operative outcomes. Notably, RRN has been increasingly utilized, especially in the setting of more advanced and surgically challenging disease without increasing the risk of peri-operative complications.

Potential vascular mechanisms in an ex vivo functional pig bladder model.

AIMS: Chronic ischemia is a recognized factor in the pathophysiology of underactive bladder (UAB). Although relative ischemia (ie, low blood flow) is known to occur during filling, little is known regarding the pathophysiology that leads to UAB. Therefore, we developed an ex vivo functional porcine model to investigate the role of transient ischemia and whether autoregulation, a mechanism that maintains tissue oxygenation in certain vital organs, also exists in the bladder. METHODS: Using bladders from slaughtered pigs, we prepared an isolated perfused model where we studied the effects of bladder perfusion flow rate on perfusion pressure and tissue oxygenation during the filling phase. Bladders were perfused at an initial flow rate of 20 mL/min and then clamped in a sequentially decreasing stepwise manner down to no flow and back to the initial flow rate. RESULTS: We found a linear relationship between flow rate and perfusion pressure until the flow rate decreased below 5 mL/min at which point the vascular resistance decreased; however, tissue pO2 remained stable after an initial decline. CONCLUSIONS: These findings suggest that there may be an intrinsic autoregulatory mechanism in the bladder that allows it to undergo cyclic episodes of relative ischemia during its normal function. Factors that overcome this mechanism such as complete or chronic ischemia may be critical in the progression to detrusor underactivity and thereby highlight the importance of intervention during the early phases of this disease process.

How I treat priapism.

Priapism is a disorder of persistent penile erection unrelated to sexual interest or desire. This pathologic condition, specifically the ischemic variant, is often associated with devastating complications, notably erectile dysfunction. Because priapism demonstrates high prevalence in patients with hematologic disorders, most commonly sickle cell disease (SCD), there is significant concern for its sequelae in this affected population. Thus, timely diagnosis and management are critical for the prevention or at least reduction of cavernosal tissue ischemia and potential damage consequent to each episode. Current guidelines and management strategies focus primarily on reactive treatments. However, an increasing understanding of the molecular pathophysiology of SCD-associated priapism has led to the identification of new potential therapeutic targets. Future agents are being developed and explored for use in the prevention of priapism.

Long-term sexual health outcomes in men with classic bladder exstrophy.

OBJECTIVES: To identify the long-term sexual health outcomes and relationships in men born with classic bladder exstrophy (CBE). MATERIALS AND METHODS: A prospectively maintained institutional database comprising 1248 patients with exstrophy-epispadias was used. Men aged ≥18 years with CBE were included in the study. A 42-question survey was designed using a combination of demographic information and previously validated questionnaires. RESULTS: A total of 215 men met the inclusion criteria, of whom 113 (53%) completed the questionnaire. The mean age of the respondents was 32 years. Ninety-six (85%) of the respondents had been sexually active in their lifetime, and 66 of these (58%) were moderately to very satisfied with their sex life. The average Sexual Health Inventory for Men score was 19.8. All aspects of assessment using the Penile Perception Score questionnaire were on average between 'very dissatisfied' and 'satisfied'. Thirty-two respondents (28%) had attempted to conceive with their partner. Twenty-three (20%) were successful in conceiving, while 31 (27%) reported a confirmed fertility problem. A total of 31 respondents (27%) reported undergoing a semen analysis or post-ejaculatory urine analysis. Of these, only four respondents reported azoospermia. CONCLUSION: Patients with CBE have many of the same sexual and relationship successes and concerns as the general population. This is invaluable information to give to both the parents of boys with CBE, and to the boys themselves as they transition to adulthood.

Overactive bladder in adults with sickle cell disease.

AIMS: To characterize the prevalence and impact of nocturnal enuresis and overactive bladder (OAB) symptomatology in the adult sickle-cell disease (SCD) population. METHODS: We performed a single-center, cross-sectional study of adult SCD patients from October 2012 to February 2014, using the validated Pfizer OAB short form questionnaire and brief voiding history surveys. Patient responses and scores were compared to that of controls having normal or sickle cell trait hemoglobin genotypes. RESULTS: A group of 239 SCD patients (116 males, 123 females) were compared with 104 normal and 57 sickle cell trait patients. Seven of 239 (2.9%) SCD patients compared to none of the 161 patients without SCD (P = 0.04) reported current nocturnal enuresis. The median age of nocturnal enuresis cessation was higher in SCD patients (12.0, IQR 9.0-15.0 years) compared to that of both normal (7.5, IQR 6.0-9.8 years) and sickle cell trait (7.5, IQR 6.0-8.8 years) groups (P < 0.0001). Ninety-three of 239 (38.9%) SCD patients compared to 17 of 104 (16.3%) normal and 11 of 57 (19.3%) sickle cell trait had scores indicating OAB symptomatology (P < 0.0001). Patients with SCD had higher OAB symptom severity and lower health-related quality of life (HRQL) scores compared to the normal and sickle cell trait groups (P < 0.0001 and P < 0.0001, respectively). CONCLUSIONS: We demonstrate an elevated rate of nocturnal enuresis and OAB symptoms in the adult SCD population. An OAB phenotype may be an under-recognized complication of SCD irrespective of age. Neurourol. Urodynam. 35:642-646, 2016. © 2015 Wiley Periodicals, Inc.

Sexual Health Outcomes in Adults with Complete Male Epispadias.

PURPOSE: Complete male epispadias is a rare congenital anomaly characterized by failed closure of the entire penopubic dorsal urethra. Epispadias repair is typically performed during infancy, and resultant genitourinary abnormalities can have a marked impact on adult life. We assess long-term post-reconstruction sexual health and fertility outcomes in adults with complete male epispadias. MATERIALS AND METHODS: A total of 132 patients 18 years or older with complete male epispadias who had undergone reconstruction were identified from a prospectively maintained, institutionally approved database. Patients who could be contacted were asked to complete a telephone survey regarding sexual function. Reconstructive history and clinical details were obtained by chart/database review. RESULTS: Of 132 patients with complete male epispadias 74 met inclusion criteria and 15 (20%) completed the questionnaire. Seven patients (47%) reported currently being in a relationship. Although 12 patients (80%) reported overall satisfactory sexual intercourse, 11 (73%) admitted to 1 or more problems with sexual function, including abnormal ejaculation (53%), diminished sensation (20%) and difficulty maintaining an erection (20%). When questioned regarding the importance of fertility on a scale of 0 to 5 using a Likert-type item the response of 10 patients (67%) was 4 points or greater. Five patients (33%) reported having impregnated a sexual partner. Although 4 patients (27%) had suspicion of fertility problems, only 2 (13%) reported having abnormal semen analyses. CONCLUSIONS: This is one of few studies examining post-reconstruction sexual health and function in adults with complete male epispadias. Although small, our study demonstrates that patients are able to engage in relationships, participate in sexual intercourse and impregnate their partners. These results highlight sexual concerns and outcomes that may be of use when counselling patients with complete male epispadias and their families.

Erectile dysfunction after sickle cell disease-associated recurrent ischemic priapism: profile and risk factors.

INTRODUCTION: Risk factors associated with erectile dysfunction (ED) that results from recurrent ischemic priapism (RIP) in sickle cell disease (SCD) are incompletely defined. AIM: This study aims to determine and compare ED risk factors associated with SCD and non-SCD-related "minor" RIP, defined as having ≥2 episodes of ischemic priapism within the past 6 months, with the majority (>75%) of episodes lasting <5 hours. METHODS: We performed a retrospective study of RIP in SCD and non-SCD patients presenting from June 2004 to March 2014 using the International Index of Erectile Function (IIEF), IIEF-5, and priapism-specific questionnaires. MAIN OUTCOME MEASURES: Prevalence rates and risk factor correlations for ED associated with RIP. RESULTS: The study was comprised of 59 patients (40 SCD [mean age 28.2 ± 8.9 years] and 19 non-SCD [15 idiopathic and four drug-related etiologies] [mean age 32.6 ± 11.7 years]). Nineteen of 40 (47.5%) SCD patients vs. four of 19 (21.1%) non-SCD patients (39% overall) had ED (IIEF <26 or IIEF-5 <22) (P = 0.052). SCD patients had a longer mean time-length with RIP than non-SCD patients (P = 0.004). Thirty of 40 (75%) SCD patients vs. 10 of 19 (52.6%) non-SCD patients (P = 0.14) had "very minor" RIP (episodes regularly lasting ≤2 hours). Twenty-eight of 40 (70%) SCD patients vs. 14 of 19 (73.7%) non-SCD patients had weekly or more frequent episodes (P = 1). Of all patients with very minor RIP, ED was found among 14 of 30 (46.7%) SCD patients vs. none of 10 (0%) non-SCD patients (P = 0.008). Using logistic regression analysis, the odds ratio for developing ED was 4.7 for SCD patients, when controlling for RIP variables (95% confidence interval: 1.1-21.0). CONCLUSIONS: ED is associated with RIP, occurring in nearly 40% of affected individuals overall. SCD patients are more likely to experience ED in the setting of "very minor" RIP episodes and are five times more likely to develop ED compared with non-SCD patients.

External validation of a prediction model for penile prosthesis implantation for erectile dysfunction management.

INTRODUCTION: Penile prosthesis implantation (PPI) is the definitive surgical treatment for erectile dysfunction (ED), yet it is often delayed for a variety of reasons. From commercial and Medicare claims data, we previously developed a tool for determining a patient's likelihood of eventually receiving PPI. We validated this instrument's utility by comparing cohorts receiving surgical (PPI) versus non-surgical ED management at a single institution. MATERIAL AND METHODS: The prediction model was based on a logistic regression incorporating claims data on demographics, comorbidities and ED therapy. A risk score is calculated from the model as the product of relative risks for the individual variables. The current validation was a retrospective analysis of ED patients seen at this institution from January to December 2012. Inclusion criteria included ED diagnosis and either first-time PPI or non-surgical treatment (controls). Risk scores for patients receiving PPI were compared to those of non-surgical controls. RESULTS: We established a cohort of 60 PPI patients (mean age 54.4 ± 9.5) and compared them with 120 non-PPI patients (mean age 53.4 ± 11.2 years). The median score of the PPI cohort was 5.7 (IQR 2.8-9.9) versus the non-PPI cohort's 1.8 (IQR 0.9-5.5) (p < 0.0001). The area under the receiver operator characteristic curve for predicting eventual PPI was 0.72 (95% CI, 0.64-0.79) (p < 0.0001). CONCLUSION: The prediction model risk-stratified men who ultimately underwent PPI compared to non-surgically managed controls. This external validation study suggests that the prediction model may be used on an individual patient basis to support a recommendation of PPI for managing ED.

Genitourinary Blastomycosis in a Young Male Patient: A Case Report and Review of Diagnostic Challenges.

Disseminated blastomycosis is an endemic fungal infection that rarely manifests with genitourinary involvement. We present a unique case of a 28-year-old professional male gamer with a remote history of hemoptysis and cervical lymphadenopathy who presented with hematospermia, lower urinary tract symptoms (LUTS), and persistent groin abscesses after left orchiectomy at an outside hospital. He underwent drainage of groin abscess and prostate biopsy for an abnormal digital rectal exam which revealed disseminated blastomycosis requiring systemic, long-term antifungal treatment. We have also included a review of literature to note clinical patterns in presentations and highlight the diagnostic challenges that this infection presents.

Unusual Cause of Artificial Urinary Sphincter Malfunction: Device Entanglement Resulting in Urethral Constriction and Urinary Retention.

Urinary retention following placement of an artificial urinary sphincter (AUS) is not an uncommon complication. We describe a unique case of urinary retention due to AUS entanglement causing urethral constriction in a 72-year-old male. He presented to the emergency department postoperatively following AUS placement with pelvic pain and incomplete emptying. Eventual cystourethroscopy demonstrated severe extrinsic urethral constriction despite the deactivation of the AUS device. Surgical exploration revealed an unexpected looping of the occlusive cuff, causing urethral constriction. Although the precise cause is not clearly known, we suspect that it may have been related to the process of connecting the tubing at the level of the abdomen. Regardless of the underlying etiology, this case highlights a unique complication and supports an assessment of the cuff with direct perineal inspection prior to wound closure and/or with cystourethroscopy.

Corpus spongiosum flap: a unique technique in the management of urosymphyseal fistula.

Urosymphseal fistulas are a debilitating but treatable consequence of the combination of radiotherapy and endoscopic interventions in prostate cancer patients. Treatment includes fistula excision with a tissue flap to prevent communication of involved structures and provide structural and vascular support. We introduce a unique surgical approach of mobilizing and utilizing a corpus spongiosum flap in urosymphyseal fistula repair. A retrospective study identified two patients who underwent repair with a pedicled corpus spongiosum flap at our institution. The corpus spongiosum had adequate length and vascularization and limited the need for extra-pelvic muscle flaps, thus maintaining muscle integrity in the abdomen and thighs. Following extirpative surgery, both patients had durable fistula closure, decreased pelvic pain, and resolution of lower urinary tract symptoms and osteomyelitis. These cases highlight the potential of the corpus spongiosum to be a reasonable alternative interpositional flap in genitourinary reconstruction.

Depression phenotypes in spinal cord injury and impact on post-injury healthcare utilization and cost: Analysis using a large claim database.

CONTEXT/OBJECTIVE: Depression is the most common psychological comorbidity associated with spinal cord injury (SCI) and affects healthcare utilization and costs. This study aimed to use an International Classification of Disease (ICD) and prescription drug-based depression phenotypes to classify people with SCI, and to evaluate the prevalence of those phenotypes, associated risk factors, and healthcare utilization. DESIGN: Retrospective Observational Study. SETTING: Marketscan Database (2000-2019). PARTICIPANTS: Individuals with SCI were classified into six ICD-9/10, and prescription drugs defined phenotypes: Major Depressive Disorder (MDD), Other Depression (OthDep), Antidepressants for Other Psychiatric Conditions (PsychRx), Antidepressants for non-psychiatric condition (NoPsychRx), Other Non-depression Psychiatric conditions only (NonDepPsych), and No Depression (NoDep). Except for the latter, all the other groups were referred to as "depressed phenotypes". Data were screened for 24 months pre- and 24 months post-injury depression. INTERVENTIONS: None. OUTCOME MEASURES: Healthcare utilization and payments. RESULTS: There were 9,291 patients with SCI classified as follows: 16% MDD, 11% OthDep, 13% PsychRx, 13% NonPsychRx, 14% NonDepPsych, 33% NoDep. Compared with the NoDep group, the MDD group was younger (54 vs. 57 years old), predominantly female (55% vs. 42%), with Medicaid coverage (42% vs. 12%), had increased comorbidities (69% vs. 54%), had fewer traumatic injuries (51% vs. 54%) and had higher chronic 12-month pre-SCI opioid use (19% vs. 9%) (all P < 0.0001). Classification into a depressed phenotype before SCI was found to be significantly associated with depression phenotype post-SCI, as evidenced by those who experienced a negative change (37%) vs. a positive change (15%, P < 0.0001). Patients in the MDD cohort had higher healthcare utilization and associated payments at 12 and 24 months after SCI. CONCLUSION: Increasing awareness of psychiatric history and MDD risk factors may improve identifying and managing higher-risk patients with SCI, ultimately optimizing their post-injury healthcare utilization and cost. This method of classifying depression phenotypes provides a simple and practical way to obtain this information by screening through pre-injury medical records.

Cancer risk in bladder diverticula: a large institutional analysis of risk and management.

PURPOSE: Bladder diverticula (BD) are usually asymptomatic, but may increase the risk of infections, stones, or malignancy, likely due to urinary stasis within the BD. We aim to characterize the risk of bladder cancer (BC) within diverticula. METHODS: Retrospective review was conducted of patients diagnosed with BD between 1994 and 2021 at a single institution. Cancer risk was characterized using descriptive statistics and multivariable logistic regression as appropriate. RESULTS: We identified 764 patients with mean age 68 years, the majority of whom were male (87%) and Caucasian (86%). Of this total, 13.3% (102/764) had a diagnosis of BC and 35.3% of this subset (36/102) had definitive cancer within the BD. Diverticulectomy or partial cystectomy was performed in 13.6% (104/764), 76% of whom were preoperatively presumed to have benign disease. Surgical patients were younger and had larger BD. Of the 79 patients who underwent diverticulectomy without preoperative suspicion for cancer, 5 were incidentally diagnosed with BC on final pathology. On multivariable logistic regression, male gender [odds ratio (OR) = 2.6, p = 0.03] and increasing age (OR = 1.02, p = 0.03) were independent risk factors for BC diagnosis. Indwelling catheter, recurrent urinary tract infections (UTIs), and bladder stones did not affect the risk of BC. CONCLUSIONS: The majority of patients with BD are not managed with surgery. BC is identified in a small but considerable proportion of patients with BD, with an even lower rate of incidentally diagnosed cancer among those undergoing BD surgery. Male gender and increasing age increased the risk of BC diagnosis.

Health Care Utilization and Cost Associated With Urinary Tract Infections in a Privately Insured Spinal Cord Injury Population.

Background: Urinary tract infections (UTIs) are the most common secondary medical complication following spinal cord injury (SCI), significantly impacting health care resource utilization and costs. Objectives: To characterize risk factors and health care utilization costs associated with UTIs in the setting of SCI. Methods: IBM's Marketscan Database from 2000-2019 was utilized to identify individuals with traumatic SCI. Relevant ICD-9 and ICD-10 codes classified individuals into two analysis groups: having ≥ 1 UTI episode or no UTI episodes within 2 years following injury. Demographics (age, sex), insurance type, comorbidities, level of injury (cervical, thoracic, lumbar/sacral), and health care utilization/payments were evaluated. Results: Of the 6762 individuals retained, 1860 had ≥ 1 UTI with an average of three episodes (SD 2). Younger age, female sex, thoracic level of injury, noncommercial insurance, and having at least one comorbidity were associated with increased odds of UTI. Individuals with a UTI in year 1 were 11 times more likely to experience a UTI in year 2. As expected, those with a UTI had a higher rate and associated cost of hospital admission, use of outpatient services, and prescription refills. UTIs were associated with 2.48 times higher cumulated health care resource use payments over 2 years after injury. Conclusions: In addition to bladder management-related causes, several factors are associated with an increased risk of UTIs following SCI. UTI incidence substantially increases health care utilization costs. An increased understanding of UTI-associated risk factors may improve the ability to identify and manage higher risk individuals with SCI and ultimately optimize their health care utilization.

Management of Urosymphyseal Fistula and Pelvic Osteomyelitis: A Comprehensive Institutional Experience and Improvements in Pain Control.

BACKGROUND: Urosymphyseal fistula (USF) is an uncommon but painful and devastating condition typically occurring after radiotherapy for pelvic malignancy, with a delayed diagnosis and a risk of opioid dependence. OBJECTIVE: To characterize our institutional experience and determine the impact of intervention for USF on pain control and opioid use. DESIGN, SETTING, AND PARTICIPANTS: We evaluated data for 33 adult patients diagnosed with USF and managed at a quaternary institution between 2009 and 2021. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed chronic opioid use, pain scores, prior therapy for pelvic malignancy, prior endoscopic procedures, microbiology and histology congruence, and postoperative complications. For comparative analyses we used a χ2 test or Fisher's exact test for categorical variables and a Wilcoxon signed-rank test for continuous variables. RESULTS AND LIMITATIONS: Nearly 94% of the patients had received prior pelvic radiotherapy and >80% occurred in 2016-2021 but were not diagnosed until a median of 10 mo (interquartile range [IQR] 3.5-19.5) following endoscopic procedure(s). Osteomyelitis was suspected in 78.8% of imaging reports and nearly 70% had a positive preoperative urine culture. Over 90% of patients underwent cystectomy, pubic bone debridement or resection, and a soft-tissue pedicle flap. Preoperative urine cultures were concordant with 60% of intraoperative tissue/bone cultures. Histologic osteomyelitis was identified in 85% and concordant with 80% of preoperative imaging. Clavien-Dindo grade ≥3 complications occurred in 15.6%. The median pain score decreased from 4 (IQR 0-8) preoperatively to 0 (IQR 0) postoperatively (p < 0.001). Chronic opioid use decreased from 39.4% to 21.2% (p = 0.02). CONCLUSIONS: Pelvic osteomyelitis may complicate USF and commonly manifests with severe, persistent pain. USF incidence may be increasing or at least increasingly recognized, but diagnosis is delayed. Definitive management results in significant improvements in pain perception and a decrease in chronic opioid use. PATIENT SUMMARY: We examined features of urinary fistulas, which are abnormal openings or connections between part of the urinary tract and another structure. Patients with a urinary fistula involving the pelvic bones can present with severe pain, but diagnosis of the condition is often delayed. Removal of some pelvic bone with bladder removal or repair can result in a decrease in long-term pain and in the use of opioid drugs for pain relief.

Urosymphyseal fistulas in women: identification and characterization of a previously undescribed phenomenon.

Urosymphyseal fistula (USF) is a very uncommon but catastrophic condition which typically occurs in the setting of previous radiation treatment for prostate cancer. As a result, USF has only been described in male populations. For the first time, we characterize this phenomenon in a series consisting of four women managed at our quaternary institution. We found that most patients presented with pubic pain and all were diagnosed with USF on CT or MRI. Imaging commonly demonstrated features suggesting osteomyelitis which was confirmed on histology. Patients experienced significant decreases in peri-operative pain scores following extirpative surgery with urinary diversion, bone debridement/resection and tissue interposition. This case series highlights the rarity of USF in women in order to help promote increased recognition and timely management.

Effect of Obesity and Overweight Status on Complications and Survival After Minimally Invasive Kidney Surgery in Patients with Clinical T2-4 Renal Masses.

Objective: To evaluate the effect of obesity and overweight on surgical, functional, and survival outcomes in patients with large kidney masses after minimally invasive surgery. Materials and Methods: Within a multicenter multinational dataset, patients found to have ≥cT2 renal mass and treated with minimally invasive (laparoscopic or robotic) kidney surgery (radical or partial nephrectomy) during the period 2003 to 2017 were abstracted. They were stratified according to the body mass index classes as normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30.0 kg/m2). Mixed models and Cox proportional hazard regression tested differences in complication rates, estimated glomerular filtration rate (eGFR) change over time, overall mortality (OM), and disease recurrence (DR) rates. Results: Of 812 patients, 30.6% were normal weight, 42.7% were overweight, and 26.7% obese. Overweight (odds ratio 0.82, 95% confidence interval [CI]: 0.51-1.31, p = 0.406) and obese patients (OR: 0.81, 95% CI: 0.44-1.47, p = 0.490) experienced similar complication rates than normal weight. Moreover, no statistically significant differences in eGFR were found for overweight (p = 0.129) or obese (p = 0.166) patients compared to normal weight. However, higher OM rates were recorded in overweight (hazard ratio [HR] 3.59, 95% CI: 1.03-12.51, p = 0.044), as well as in obese, patients (HR 7.83, 95% CI: 2.20-27.83, p = 0.002). Similarly, higher DR rates were recorded in obese (HR 2.76, 95% CI: 1.40-5.44, p = 0.003) patients. Conclusions: Obese and overweight patients do not experience higher complication rates or worse eGFR after minimally invasive kidney surgery, which therefore can be deemed feasible and safe also in this subset of patients. Nevertheless, obese and overweight patients seem to carry a higher risk of OM, and therefore, they should undergo a strict follow-up after surgery.

Dysregulated NO/PDE5 signaling in the sickle cell mouse lower urinary tract: Reversal by oral nitrate therapy.

AIMS: Nitric oxide (NO) has a critical, but not well understood, influence in the physiology of the lower urinary tract. We evaluated the effect of NO/phosphodiesterase (PDE)5 signaling in voiding dysfunction in the sickle cell disease (SCD) mouse, characterized by low NO bioavailability. MAIN METHODS: Adult SCD (Sickle) and wild-type (WT) male mice were treated daily with sodium nitrate (10 mM) or vehicle. After 18 days, blood was obtained for nitrite measurement, urethra was collected for organ bath study, and bladder and urethra were collected for Western blot analysis of PDE5 phosphorylation (Ser-92) (activated form). Non-anesthetized mice underwent evaluation of urine volume by void spot assay. eNOS phosphorylation (Ser-1177) and nNOS phosphorylation (Ser-1412) (positive regulatory sites) were evaluated in the bladder and urethra of untreated mice. KEY FINDINGS: Sickle mice exhibited decreased eNOS, nNOS, and PDE5 phosphorylation in the bladder and urethra, decreased plasma nitrite levels, increased relaxation of phenylephrine-contracted urethral tissue to an NO donor sodium nitroprusside, and increased total urine volume, compared with WT mice. Nitrate treatment normalized plasma nitrite levels, relaxation of urethra to sodium nitroprusside, PDE5 phosphorylation in the urethra and bladder, and urine volume in Sickle mice. SIGNIFICANCE: Derangement in PDE5 activity associated with basally low NO bioavailability in the bladder and urethra contributes to the molecular basis for voiding abnormalities in Sickle mice. Inorganic nitrate supplementation normalized voiding in Sickle mice through mechanisms likely involving upregulation of PDE5 activity. These findings suggest that interventions targeting dysregulatory NO/PDE5 signaling may ameliorate overactive bladder in SCD.