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BACKGROUND: Radical cystectomy (RC) has the potential for profound changes to health-related quality of life (HRQOL). OBJECTIVE: To evaluate a broad range of HRQOL outcomes in a large RC cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-center prospective study enrolled RC patients from 2008 to 2014. We collected 14 separate patient-reported outcome measures at the presurgical visit and at 3, 6, 12, 18, and 24 mo after RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: To visualize the patterns of recovery over time across domains, we used generalized estimating equations (GEEs) with nonlinear terms. Given substantial differences in patient selection for the type of urinary diversion, we separately modeled longitudinal HRQOL within conduit and continent diversion groups. The mean pre-RC scores were compared to illustrate the baseline HRQOL differences between diversion groups. RESULTS AND LIMITATIONS: The analyzed cohort included 411 patients (n = 205 ileal conduit, n = 206 continent diversion). At baseline, patients receiving continent diversion reported better mean physical (p < 0.001), urinary (p = 0.006), and sexual function (p < 0.001), but lower social function (p = 0.015). After RC, GEE modeling showed physical function scores decreasing 5/100 points by 6 mo, and subsequently stabilizing or returning to baseline. By 12 mo, social function improved by 10/100 points among continent diversions, while remaining stable among ileal conduits. Global quality of life exceeded baseline scores by 6 mo. Sexual function scores were low before RC, with limited recovery. Psychosocial domains were stable or improved, except for 10/100-point worsening of body image among ileal conduits. CONCLUSIONS: RC patients reported favorable HRQOL recovery within 24 mo in most areas other than body image (ileal conduits) and sexual function (both). Importantly, large measurable decreases in scores were not reported by 3 mo after RC. These contemporary outcomes and the excellent locoregional control provided by RC further support it as the gold standard therapy for high-risk bladder cancer. PATIENT SUMMARY: We review quality of life in the 24 mo following radical cystectomy. Large decreases in health-related quality of life were not reported, with most areas returning to, or exceeding, baseline, except for sexual function and body image.

Complete androgen insensitivity syndrome is a rare disorder. Primary amenorrhea beyond 14 years of age without, and 16 years along with developed secondary sexual characters should raise suspicion of this entity as a cause. Inguinal examination may confirm presence of inguinal gonads. The absence of female internal genitalia on imaging, absence of pubic/axillary hair, and chromosomal analysis clinch the diagnosis. Surgical excision of gonads to prevent malignancy, estrogen supplementation, and vaginoplasty along with psychological counselling remain the mainstay of treatment.

Background The 3-piece inflatable penile prosthesis includes an easy-to-use pump and fluid filled reservoir which is placed in either the space of Retzius (SOR) or in an alternative ectopic location. Reservoir placement in the SOR is a blind procedure despite the SOR being surrounded by many critical structures. To date only a handful of cadaveric studies have described the relevant anatomy. Aim To use magnetic resonance imaging (MRI) as an in-vivo model to study relevant retropubic anatomy critical for SOR reservoir placement. Methods The study population included men with elevated prostate specific antigen or biopsy proven prostate cancer who (i) underwent pelvic MRI, (ii) without prior pelvic or inguinal surgery, and (iii) without pelvic radiation therapy. All MRIs were completed with a 3-Tesla scanner and endorectal coil. Both T1 and T2 weighted images were captured in both axial and sagittal planes. All images were reviewed by 2 independent reviewers under the supervision of a dedicated body MRI radiologist. Bladder volume was calculated using an ellipsoid formula. Outcomes Relevant measurements included (i) the distance between the external inguinal ring (EIR) at the level of the pubic tubercle to the external iliac vein (EIV), (ii) the distance from the EIR at the pubic tubercle to the bladder (accounting for bladder volume) and (iii) the distance from the midline pubic symphysis to the bladder (accounting for bladder volume). Pearson correlation was used to determine correlated measurements. RESULTS A total of 24 patients were included. Median participant age was 63 years (interquartile range, 59-66). The mean EIR-EIV distance was 3.0 ± 0.4 cm, the mean EIR-bladder distance was 1.8 ± 1.0 cm and the mean distance from the superior pubic symphysis to bladder was 0.9 ± 0.3 cm. There was a weak correlation between bladder volume and distance between the EIR and bladder (r = -0.30, P = .16). Clinical Implications The use of MRI as an in-vivo model is a high-fidelity tool to study real time unaltered anatomy and allows for surgical preparation, diagnosis of anatomic variants and acts as a valuable teaching tool. Strengths & Limitations This is the first in-vivo model to report relevant retropubic anatomy in penile implant surgery. Our study is limited by sample size and inclusion of participants with no history of prior pelvic intervention. CONCLUSION We demonstrate the utility of MRI as an in-vivo model, as opposed to cadaveric models, for the understanding of relevant retropubic anatomy for implant surgeons.

Urinary incontinence is a common and predictable consequence among men with localized prostate cancer who have undergone radical prostatectomy. Despite advances in the surgical technique, urinary continence recovery time remains variable. A range of surgical and patient-related risk factors contributing to urinary incontinence after radical prostatectomy have been described, including age, BMI, membranous urethral length and urethral sphincter insufficiency. Physical activity interventions incorporating aerobic exercise, resistance training and pelvic floor muscle training programmes can positively influence the return to continence in men after radical prostatectomy. Traditional approaches to improving urinary continence after radical prostatectomy have typically focused on interventions delivered during the postoperative period (rehabilitation). However, the limited efficacy of these postoperative approaches has led to a shift from the traditional reactive model of care to more comprehensive interventions incorporating exercise-based programmes that begin in the preoperative period (prehabilitation) and continue after surgery. Comprehensive prehabilitation interventions include appropriately prescribed aerobic exercise, resistance training and specific pelvic floor muscle instruction and exercise training programmes. Transperineal ultrasonography is a non-invasive and validated method for the visualization of the action of the pelvic floor musculature, providing real-time visual biofeedback to the patient during specific pelvic floor muscle instruction and training. Importantly, the waiting time before surgery can be used for the delivery of comprehensive prehabilitation exercise-based interventions to increase patient preparedness in the lead-up to surgery and optimize continence and health-related quality-of-life outcomes following radical prostatectomy., Incontinence is a common complication of radical prostatectomy and can have a considerable effect on quality of life for men who have survived prostate cancer. In the past, management of postoperative incontinence has focused on rehabilitation and postsurgical management, but prehabilitation, in the form of pelvic floor muscle exercises and training, has the potential to improve postprostatectomy continence outcomes, provide patients with agency for their own health and improve quality of life in men who have been treated for prostate cancer., Key points The oncological curative effectiveness of radical prostatectomy can be diminished by treatment-related adverse effects that include urinary incontinence, reduced physiological functional capacity and psychosocial well-being. The increasing survival of men following radical prostatectomy has resulted in the development of preoperative interventions that can improve the patients’ preoperative and postoperative experience and optimize health-related quality-of-life outcomes. Preoperative exercise interventions comprising a combination of aerobic exercise, resistance training and specific pelvic floor muscle training programmes are designed to enhance the patients’ physiological functional capacity and mitigate the treatment-related adverse effects of radical prostatectomy including urinary incontinence. Transperineal ultrasonography can provide a non-invasive and validated method to improve the quality and specificity of the delivery of pelvic floor muscle training interventions in men before and after they undergo radical prostatectomy. A structured and coordinated prehabilitation model of care can be initiated by the surgeon and delivered through their multidisciplinary team to extend the surgical care provided to patients and optimize preoperative and postoperative functional outcomes.

Radical cystectomy/urinary diversion is a high risk procedure. Intraoperative stents are commonly utilized to decrease ureteroenteric anastomosis related complications. Institutionally some surgeons routinely use intraoperative stents while others do not, providing an opportunity to compare complication differences.We queried a prospective database of 283 patients enrolled in a randomized controlled trial evaluating 30-day perioperative complications with goal directed fluid therapy following open radical cystectomy/urinary diversion between 2014 and 2018. Ureteroenteric anastomosis specific complications (ureteral obstruction, urinary leak, urinary infections/sepsis and intra-abdominal abscess) were compared between groups (intraoperative stent vs nonintraoperative stent group) using Fisher exact test and quantified using logistic regression.The nonintraoperative stent group (77 of 283 patients, 27%) was older (median 72 vs 69 years) and was more likely to receive neoadjuvant chemotherapy (53% vs 40%), have baseline renal insufficiency (43% vs 30%) and undergo an ileal conduit (92% vs 53%). However, despite higher comorbidity, the nonintraoperative stent group had a significantly lower rate of ureteroenteric anastomosis complications (14% vs 32%, p=0.004). Since continent diversions may be associated with higher complications, the nonintraoperative stent group with ileal conduit was also compared to intraoperative stent cohorts with ileal conduit, and ureteroenteric anastomosis complications remained lower in the nonintraoperative stent group (14% vs 28%, p=0.043). Multivariable logistic regression showed significantly increased odds of urinary complications with intraoperative stent use (OR 3.55, 95% CI 2.93-4.31; p0.0001). Importantly there was no obstruction and only 1 leak (1.3%) in the nonintraoperative stent group.Contrary to conventional belief, we found intraoperative stent use in radical cystectomy/urinary diversion was associated with significantly higher infectious complications and urgent care visits, and significantly increased the odds of 30-day ureteroenteric anastomosis associated complications.

Voiding dysfunction is common after surgical and radiation treatments in patients diagnosed with non-urological pelvic malignancies. Presentation might vary with lower urinary tract symptoms and/or overactive bladder, urinary retention, or incontinence. We reviewed the most recent literature with the aim of describing various types of urinary dysfunction that manifest after radical treatments for non-urological pelvic malignancies. Radical surgical or radiation treatment adversely affect other adjacent pelvic organ function, including viscera, pelvic musculature and the peripheral nervous system. This results in direct organ and indirect functional damage to the genitourinary tract. Multiple surgical and radiation modifications are available nowadays, allowing urologists to offer various treatments for better functional lower urinary tract outcomes. Diagnosing and understanding the type and severity of voiding dysfunction plays a key role in tailoring an appropriate treatment plan. The objective to better functional results relies on maintaining adequate bladder compliance and capacity while permitting volitional emptying, ideally through voiding. Management should routinely start with conservative measures, including pelvic floor muscle training with or without a combination of oral medication for urgency incontinence and clean intermittent catheterization for the management of urinary retention. Concomitant or isolated urinary incontinence can be further managed through multiple established surgical approaches. We attempted to address various treatment available for known lower urinary tract symptoms that might have been caused secondary to non-urological pelvic surgery or radiation. We discuss different diagnostic and treatment modalities individualized for patients with various entities, to help achieve optimal urinary function and improve quality of life.

OBJECTIVE: To determine predictors of symptomatic uretero-enteric anastomotic strictures (UAS) formation following radical cystectomy (RC) and urinary diversion (UD). MATERIALS AND METHODS: 2,888 consecutive patients who underwent open RC at our institution from 1995–2014 were included for analysis. Data was collected from institutional databases and individual medical records. Symptomatic benign UAS was defined as percutaneous nephrostomy tube insertion for rising creatinine or unilateral hydronephrosis comparing pre- and post-operative imaging. Univariate and multivariable Cox proportional hazards models were utilized to identify features associated with UAS formation. RESULTS: UAS developed in 123/2,888 patients following RC. There were 94 symptomatic and 29 asymptomatic strictures. Median follow-up was 32 months (IQR 12, 72) for patients without stricture. Higher BMI (p=0.002), ASA score >2 (p2, lymph node involvement, grade III/IV complications within 30 days, male sex, and a history of PAS. We conclude that while surveillance is important for patients who undergo cystectomy for malignancy, it may be beneficial for patients with history of PAS undergo more intensive follow-up compared to those patients without history of PAS.

Background After radical prostatectomy (RP), climacturia is a prevalent and distressing problem. To date, no specific predictors have been identified. Aim In this analysis, we sought to find associated pelvic magnetic resonance imaging (MRI) parameters. Methods We identified all men in our departmental database who (i) had climacturia post-RP, ≥3 episodes; (ii) underwent a pre-RP endorectal MRI; (iii) had no radiation or androgen deprivation therapy (ADT). Soft tissue and bony dimensions were measured by 2 raters blinded to clinical and pathological data. Outcomes MRI parameters included the following: maximum height, width, and depth of prostate, prostate volume, urethral width and length, lower conjugate of pelvis, bony femoral width, outer and inner levator distances and thickness. Point-biserial correlations were run on univariate associations. Logistic regression was used for the multivariable model. Results 194 consecutive pre-RP MRI studies were reviewed (56 men with and 138 without climacturia). Mean age was 60 ± 7 years, average time post-RP at assessment, 7 ± 7 months. Of MRI parameters, urethral width (r = 0.13, P = .03) and lower conjugate (r = 0.12, P = .05) were associated with presence of persistent climacturia. 2 others met criteria for multivariable analysis, prostate depth and outer levator distance. Of the non-MRI parameters, none were significantly related to climacturia and only body mass index (BMI) met criteria for multivariable analysis. On multivariable analysis, only urethral width was associated with climacturia (OR = 1.23, 95% CI: 1.01–1.49, P = .04); the wider the urethra, greater the chance of climacturia. Clinical Implications Improved ability to predict the occurrence of orgasm-associated incontinence in the preoperative setting. Strengths and Limitations Limitations include the fact that the MRI endorectal probe may have distorted pelvic tissues during imaging and that our study population size was small. However, prospective data collection, blinded measurements by 2 trained readers, and rigorous statistical analysis should be considered strengths. Conclusion By identifying preoperative risk factors, such as urethral width on MRI, we may be able to better understand the pathophysiology of this condition and furthermore may permit us to better counsel men regarding this postoperative outcome.

INTRODUCTION: After RP, clinical complaints of new onset storage symptoms may be related to anastomotic strictures or as accommodation for stress urinary incontinence; however, a subgroup of men will experience de novo storage symptoms in the absence of stricture or stress urinary incontinence. As therapies for OAB have improved, we sought to assess the prevalence, natural history, and risk factors of de novo storage dysfunction in continent men. METHODS: We retrospectively analyzed urinary symptom questionnaires completed by patients who were continent prior to RP and did not have post-operative anastomotic strictures at our institution from 2002–2019. De novo storage dysfunction, assessed as new onset or worsening urgency or frequency was assessed at 6, 12, 18 and 24 months after RP and association between it and patient and preoperative factors determined. RESULTS: A total of 2619 patients were included in the final analysis. An initial 34% of patients reported de novo storage symptoms at 6 months, which decreased to 26% at later follow-up. We found evidence that minimally invasive surgery and non-white race were associated with reporting worsening symptoms. The association between post-operative hematoma and worsening symptoms was less conclusive but was of clear clinical relevance (OR 3.15; 95% CI 1.04, 9.54; p-value = 0.042). CONCLUSION: A significant number of RP patients experience de novo storage symptoms. Patients who underwent MIS surgery are at higher risk. At risk patients should be counseled on the incidence of de novo storage symptoms and offered early treatment per OAB guidelines.

Objective To determine the durability of ureteroneocystostomy as well as pre- or post-operative factors that may be associated with failure to provide appropriate renal drainage. Methods A total of 290 patients who underwent ureteral reimplantation to native bladder between 2003 and 2015 were identified. After excluding pediatric patients and those without any follow-up, 255 patients, 3 of whom had a subsequent contralateral reimplantation were included, for 258 observations. Kaplan-Meier method and univariate Cox models were used to assess whether factors such as radiation, prior abdominal surgery, age at re-implantation, gender and BMI are associated with re-implantation failure. Results Among 258 observations, there were 27 failures. Median follow-up time was 1.1 years from re-implantation surgery among patients without a failure.1 and 5-year ureteral re-implantation failure is 7% (95% CI 4%, 12%) and 22% (95% CI 15%, 33%), respectively. On univariate analysis, post-operative radiation was found to be strongly associated with poorer ureteral re-implantation survival (HR: 6.62; CI 2.40, 18.29; P = .0003) No significant association between re-implantation failure-free survival and age at reimplantation, gender, BMI, previous abdominal surgery, preoperative radiation and adjuvant radiation was noted (all P > .4). Conclusions Ureteroneocystotomy in the malignant setting has reasonable success rates through five years. No preoperative factors were associated with re-implantation failure. While all patients need to be followed due to increasing rates of failure with time, patients receiving palliative or salvage radiation therapy appear to be more prone to failure requiring further intervention.

INTRODUCTION AND OBJECTIVE:The impact of androgen deprivation therapy (ADT) on artificial urinary sphincter (AUS) outcomes is unclear, though relevant due to the increasing number of high risk pati...

INTRODUCTION AND OBJECTIVE: Padeliporfin (WST11) vascular-targeted photodynamic therapy (VTP) has shown significant clinical benefit as a localized partial gland ablation (PGA) therapy when compared to active surveillance for low-risk prostate cancer, by curbing progression and the need for radical treatment, leading to its regulatory approval in Europe. This Phase 2b trial prospectively investigated WST11-VTP for intermediate-risk cancers. METHODS: 50 men with unilateral Grade Group 2 (GG2) cancers (Gleason 3+4) evaluated with MRI and ultrasound-guided (TRUS) biopsy were treated with up to 2 sessions of unilateral PGA using padeliporfin VTP. Eligibility criteria included

INTRODUCTION AND OBJECTIVE:Radical cystectomy (RC) with urinary diversion is the gold standard therapy for high risk invasive bladder cancer, however the procedure affects multiple organ systems wi...

Urinary incontinence after prostate treatment (IPT) is one of the few urologic diseases that is iatrogenic, and, therefore, predictable and perhaps preventable. Evaluation of the incontinent patient, risk factors for IPT, the assessment of the patient prior to intervention, and a stepwise approach to management are covered in this guideline. Algorithms for patient evaluation, surgical management, and device failure are also provided.This guideline was developed using a systematic review from the Mayo Clinic Evidence Based Practice Center with additional supplementation by the authors. A research librarian conducted searches from 2000 to December 21This guideline was developed by a multi-disciplinary panel to inform clinicians on the proper assessment of patients with IPT and the safe and effective management of the condition in both surgical and non-surgical contexts. Statements guiding the clinician on proper management of device failure are also included.Most patients who undergo radical prostatectomy (RP), and some patients who undergo radiation therapy (RT) or surgery for benign prostatic hyperplasia (BPH), will experience IPT. Although non-surgical options, such as pelvic floor muscle exercises (PFME), can hasten continence recovery, patients who remain incontinent at one-year post-procedure, or have severe incontinence at six months, may elect to undergo surgical treatment (e.g. artificial urinary sphincter). Prior to IPT surgery, the risks, benefits, alternatives, and additional likely procedures should be discussed with the patient.

Purpose To develop a cadaver model for the assessment of a male transobturator male sling (retrourethral transobturator sling [RTS], AdVance™; Boston Scientific, USA) to investigate its effect on a simulated abdominal and retrograde leak point pressures (ALPP, RLPP) and the urethral pressure profile (UPP). Materials and methods Three fresh frozen human male cadaver specimens were obtained. A suprapubic tube was inserted into the bladder and connected to a digital manometer to measure bladder pressure. Manual suprapubic pressure was then applied to generate an increase in intraabdominal pressure and measure a simulated ALPP. Subsequent measurements of RLPP and UPP were recorded. All measurements were undertaken prior to and following insertion of a RTS. Results The placement of the RTS consistently increased the simulated ALPP for all three cadaver specimens when compared to baseline measures. No leaks occurred at simulated ALPP's of 170 cm H2O for specimen 1, 160 cm H2O for specimen 2, and 170 cm H2O for specimen 3. There was minimal or no change in the RLPP's and UPP's following insertion of the RTS when compared to respective baseline. Conclusions A model using fresh unfixed cadavers that incorporates a simulated measurement of ALPP is feasible for male stress urinary incontinence surgical intervention investigations.

Background There is a change in the position of the remaining anatomical structures of the lower urinary tract system following radical prostatectomy. The aims of this investigation were to describe three novel methods used to measure the displacement of i) the vesico-urethral junction (VUJ), proximal membranous urethra (PMU) and anorectal junction (ARJ) and ii) the VUJ angle of displacement in men following radical prostatectomy and determine their intra- and interrater reliability. Methods Retrospective comparative measurement of twenty pre- and postoperative MRI scans was undertaken by one observer on two separate occasions and on one occasion by another observer. Three standardized midsagittal pelvimetry reference lines were used to describe three X, Y axis measurement systems. The displacement (mm) of the VUJ, PMU and ARJ, and the angle of displacement (degrees) of the VUJ was measured for each of the three methods. Interrater reliability of VUJ, PMU and ARJ displacement and the VUJ angle of displacement measurements was assessed using a two-way mixed-effects agreement intra-class correlation coefficient (ICC) with 95% confidence intervals (CI). Test-retest (intrarater) reliability was calculated using a two-way random effects consistency ICC with 95% CI for all displacement measures of the VUJ, PMU and ARJ for one observer between two days. Results The pubococcygeal line (PCL) axis measurement system demonstrated good to excellent intrarater and interrater reliability (ICC 95% interval lower bound > 0.75) for the VUJ and PMU displacement and the VUJ angle of displacement measurements. Other measurement systems were less reliable and more variable. Conclusions In this sample of 20 Korean patients with median prostate volume 27.5 mL and maximum volume 70 mL, the measurement methodology using the PCL consistently demonstrated good to excellent reliability and the lowest variability for the measurement of the displacement of the VUJ and PMU and the VUJ angle of displacement. The PCL methodology is recommended as the method of choice. Further studies should validate these results in patients with large prostate volumes.

Objectives To explore pre-operative factors and their impact on overall survival (OS) in a modern cohort of patients who underwent pelvic exenteration (PE) for gynecologic malignancies. Methods A retrospective review was performed for all patients who underwent a PE from 1/1/2010 through 12/31/2018 at our institution. Inclusion criteria were exenteration due to recurrent or progressive carcinoma of the uterus, cervix, vagina or vulva, with histologically confirmed complete surgical resection of the malignancy. Exclusion criteria included PE for palliation of symptoms without recurrence, and for ovarian or rare histologic malignancies. Univariable and multivariable analysis were performed to identify factors predicting prolonged survival. Results Overall, 71 patients met the inclusion criteria. Median age at time of exenteration was 62 years (range, 28–86 years). Vulvar cancer was the most common primary diagnosis (32%); 30% had cervical cancer; 23%, uterine cancer; 15%, vaginal cancer. Median OS was 55.1 months (95% confidence interval (CI): 36-not estimable) with a median follow-up time of 40.8 months (95% CI: 1–116.1). On univariable analysis, age > 62 years (hazard ratio (HR) 2.71, 95% CI 1.27–5.79), American Society of Anesthesia (ASA) 3–4 (HR: 3.41 (95% CI 1.03–11.29), and vulvar cancer (HR 4.19 (95% CI 1.17–14.96) predicted worse OS. Tumor size and prior progression-free interval (PFI) did not meet statistical significance in OS analyses. On multivariable analysis, there were no significant factors associated with worse OS. Conclusions PE performed with curative intent may be considered a treatment option in well-counseled, carefully selected patients, irrespective of tumor size and PFI before exenteration.

Objective To demonstrate the safety and efficacy of photoselective vaporization of the prostate in alleviating refractory lower urinary tract symptoms in prostate cancer patients who are managed with active surveillance and to explore the association of this procedure with prostate specific antigen (PSA) levels and cancer progression rates. Methods Between 2008-2018, active surveillance patients who had refractory symptoms and needed surgery were studied. Perioperative functional variables were collected and analyzed. Disease progression was defined as an upgrade or upstage on surveillance biopsies or multiparametric prostate magnetic resonance imaging. Mean postop scores were estimated using locally-weighted methods. The risk of progression was reported using Kaplan-Meier's method. Results Seventy-one patients were included in the study. The median age was 68 years and the median surveillance time before surgery was 4 years. At 12 months, there were substantial improvements in the mean International Prostate Symptom Score (18-5.9), maximum flow rate (6.8-14 mL/s), postvoid residual (240-73mL), PSA (8.1-5.2 ng/mL), and prostate volume (85-57mL). At 30-days, only 2 patients with grade-III complications. Late consequences included tissue regrowth in 4 and urethral stricture (requiring a single dilation) in 3 patients. PSA levels decreased by 36% at 12 months postoperatively. With a median follow-up of 3.7 years, 7 men progressed and received radical treatment. At 3 years, the probability of remaining on surveillance was 93% (95% CI 87%- 100%). Conclusion Photoselective vaporization of the prostate offers substantial relief of symptoms in active surveillance patients with refractory symptoms, without adverse effects on disease progression rates.

Recent studies have demonstrated the existence of a discrete pool of cholesterol in the plasma membranes (PM) of mammalian cells-referred to as the accessible cholesterol pool-that can be detected by the binding of modified versions of bacterial cytolysins (e.g., anthrolysin O). When the amount of accessible cholesterol in the PM exceeds a threshold level, the excess cholesterol moves to the endoplasmic reticulum (ER), where it regulates the SREBP2 pathway and undergoes esterification. We reported previously that the Aster/Gramd1 family of sterol transporters mediates nonvesicular movement of cholesterol from the PM to the ER in multiple mammalian cell types. Here, we investigated the PM pool of accessible cholesterol in cholesterol-loaded fibroblasts with a knockdown of Aster-A and in mouse macrophages from Aster-B and Aster-A/B-deficient mice. Nanoscale secondary ion mass spectrometry (NanoSIMS) analyses revealed expansion of the accessible cholesterol pool in cells lacking Aster expression. The increased accessible cholesterol pool in the PM was accompanied by reduced cholesterol movement to the ER, evidenced by increased expression of SREBP2-regulated genes. Cosedimentation experiments with liposomes revealed that the Aster-B GRAM domain binds to membranes in a cholesterol concentration-dependent manner and that the binding is facilitated by the presence of phosphatidylserine. These studies revealed that the Aster-mediated nonvesicular cholesterol transport pathway controls levels of accessible cholesterol in the PM, as well as the activity of the SREBP pathway.

Summary Incomplete understanding of how hepatosteatosis transitions to fibrotic non-alcoholic steatohepatitis (NASH) has limited therapeutic options. Two molecules that are elevated in hepatocytes in human NASH liver are cholesterol, whose mechanistic link to NASH remains incompletely understood, and TAZ, a transcriptional regulator that promotes fibrosis but whose mechanism of increase in NASH is unknown. We now show that increased hepatocyte cholesterol upregulates TAZ and promotes fibrotic NASH. ASTER-B/C-mediated internalization of plasma membrane cholesterol activates soluble adenylyl cyclase (sAC; ADCY10), triggering a calcium-RhoA-mediated pathway that suppresses β-TrCP/proteasome-mediated TAZ degradation. In mice fed with a cholesterol-rich NASH-inducing diet, hepatocyte-specific silencing of ASTER-B/C, sAC, or RhoA decreased TAZ and ameliorated fibrotic NASH. The cholesterol-TAZ pathway is present in primary human hepatocytes, and associations among liver cholesterol, TAZ, and RhoA in human NASH liver are consistent with the pathway. Thus, hepatocyte cholesterol contributes to fibrotic NASH by increasing TAZ, suggesting new targets for therapeutic intervention.

INTRODUCTION AND OBJECTIVE:Incontinence after radical prostatectomy is poorly understood. Preoperative factors such as age and membranous urethral length (MUL) have been shown to correlate with pos...

OBJECTIVES To present a modified technique in artificial urinary sphincter (AUS) placement that is associated with low rates of erosion and infection in a high-risk population. PATIENTS AND METHODS After Institutional Review Board approval, we identified patients who underwent primary AUS placement using the modified technique between January 2007 and November 2015. Our modification consists of preserving the dorsolateral fibromuscular tissue surrounding the bulbar urethra and horizontally transecting the ventral bulbospongiosus muscle during urethral cuff placement. Preoperative variables such as radiotherapy (RT) and bladder neck contractures were recorded. Effectiveness and complications including infections, erosions, and re-operations were recorded at follow-up. RESULTS The new technique was used on 208 patients: 40% had a history of RT, including 15% who had had a salvage radical prostatectomy; 26% had had previous bladder neck contractures. No patients developed infection. Overall, erosion occurred in six (2.9%) patients and spontaneous erosions occurred in two (0.9%) during the study period. In all, 21 patients underwent re-operation for device failure. The probability of re-operation for 'any' reason was 7% (95% confidence interval [CI] 4-12%) at 1 year. The 1-year social continence rate was 74% (95% CI 67-81%). CONCLUSION Preservation of dorsolateral fibromuscular tissue during AUS placement is an effective means to achieve a low risk of erosions. Our modified technique is safe with low infection and erosion rates, whilst maintaining good functional outcomes despite a high-risk population.

Involvement of unsaturated transport and high temperatures during frying of foods makes it a challenging process to study via experiments and computer simulations. The objective of this research is to validate the hybrid mixture based unsaturated transport theory of Takhar (2014) via controlled frying experiments. A hollow Teflon disc is used to insulate the edges of potato disc to ensure that frying is controlled, one-dimensional, and oil uptake and moisture loss happen only through top and bottom surfaces. The model was used to predict moisture and oil content, evaporation rates, temperature distribution, and pore and gas pressure profiles as a function of frying time and temperature. Percentage average absolute difference (AAD) between predicted and experimental values for moisture content was 3.89%, 5.7% and 5.5% and oil content was 14%, 31% and 20% at 150, 170 and 190 °C respectively. Simulations showed that oil penetrated to only 0.5 mm into the potato disc. Removal of surface oil improved the prediction of experimental oil content. Maximum evaporation rate of 0.13 kg/m3 s was observed near the surface of potato slice at 150 s frying time resulting in rapid moisture loss. Pore pressure remained negative beyond 90 s frying time, which may act as a driving force for oil uptake.

Objective: To compare preoperative membranous urethral length (MUL) measurements using magnetic resonance imaging (MRI) with two-dimensional transperineal ultrasound imaging (TPUS) in two supine positions on two separate days in men prior to radical prostatectomy.Materials and methods: MUL was prospectively measured in 18 male volunteers using MRI and on two separate occasions in two different patient positions using TPUS; the patient supine with the knees extended (Supine) and supine with the knees flexed to 70 degrees (Supine KF). Agreement between TPUS and MRI measurements of MUL was assessed using Bland-Altman method comparison techniques and a two-way mixed-effects single measures intraclass correlation (ICC). Test-retest reliability was assessed using a two-way random effects single measures ICC.Results: The mean difference in MUL measurements between MRI and i) TPUS Supine was -0.8 mm (95% limits of agreement (LOA): -3.2, 1.7) and ii) TPUS Supine KF was -0.8mm (95% LOA: -3.5, 1.9). ICC indicated a point estimate of excellent agreement between MRI and TPUS Supine ICC 0.93 (95% CI: 0.76, 0.98) and TPUS Supine KF ICC 0.91 (95 0 /0CI 0.79, 0.97). There was excellent agreement between TPUS Supine and TPUS Supine KF (ICC 0.98, 95% CI: 0.96, 0.99) with a mean difference of 0.3mm (95% LOA: -1.2 to 1.3mm).Conclusions: Preoperative MUL can be reliably measured using TPUS and demonstrates excellent agreement with MRI measurements of MUL. TPUS provides clinicians with an accessible non-invasive alternative to MRI for the measurement of MUL that can be used in outpatient urological settings and for patients where MRI is contraindicated.

Aims Continent urinary diversion is preferred by some patients and orthotopic urinary diversion (OUD) has become the procedure of choice for most men following cystectomy for invasive bladder cancer. OUD in women, however, is less common, likely due to a high rate of hypercontinence (HC), potentially from lax support of pelvic structures similar to pelvic organ prolapse. As such, we evaluated if abdominal sacrocolpopexy (ASC) at the time of OUD in women led to decreased rates of HC. Methods A retrospective review of all female patients receiving OUD by a single surgeon and ASC was performed. ASC was performed after RC was complete prior to the urethro-enteric anastomosis. Peritoneal flap was created to the vaginal apex. The distal leaf was then sutured to the proximal anterior vaginal wall and apex and the proximal end sutured to the anterior longitudinal ligament. HC was defined as the need to perform intermittent catheterization (IC) due to incomplete emptying of the neobladder. Results Nine women underwent cystectomy with OUD and concurrent ASC during the specified time period. Average patient age was 54 years (27-69). Mean followup was 61.6 months (5-123 months). None of those who underwent ASC had HC or incontinence post-operatively. No mesh-related complications were noted in this cohort. Pelvic abscess was noted in one patient who underwent ASC with rectus fascia. Conclusions ASC at the time of radical cystectomy and OUD is safe and effective. It appears to be associated with decreased rates of HC and is associated with minimal additional morbidity to the patient.

Nuclear receptors regulate gene expression in response to environmental cues, but the molecular events governing the cell-type specificity of nuclear receptors remain poorly understood. Here we outline a role for a non-coding RNA in modulating the cell type-specific actions of LXRs, sterol-activated nuclear receptors that regulate the expression of genes involved in cholesterol homeostasis and that have been causally linked to the pathogenesis of atherosclerosis. We identify the lncRNA MeXis as an amplifier of LXR-dependent transcription of the critical cholesterol efflux gene Abca1. Mice lacking the MeXis gene show reduced Abca1 expression in a tissue-selective manner. Furthermore, loss of MeXis in mouse bone marrow cells alters chromosome architecture at the Abca1 locus, impairs cellular responses to cholesterol overload, and accelerates the development of atherosclerosis. Mechanistic studies reveal that MeXis interacts with and guides promoter binding of the transcriptional coactivator DDX17. The identification of MeXis as a lncRNA modulator of LXR-dependent gene expression expands our understanding of the mechanisms underlying cell-type selective actions of nuclear receptors in physiology and disease., This work was support by NIH grants HL030568, HL066088, HL128822, Burroughs Wellcome Fund Career Award for Medical Scientists and UCLA Cardiovascular Discovery Fund (Lauren B. Leichtman and Arthur E. Levine Investigator Award).

Large staghorn calculi in unascended pelvic kidneys and in normally located kidneys with anatomy unsuitable for percutaneous nephrolithotomy have to be treated via pyelolithotomy. When performed laparoscopically, the extraction of these staghorn calculi, without extending skin incision at the port site is challenging. We describe the successful use of laparoscopic laser lithotripsy, intracorporeally, with the entrapped calculus inside the endocatch bag, for fragmentation and retrieval without extension of skin incision.

Objectives: To evaluate the perioperative outcomes and oncologic outcomes of patients undergoing pelvic exenteration, first described by Alexander Brunschwig in 1948, for non-ovarian gynecologic malignancies at a comprehensive cancer center. Methods: All patients who underwent exenteration at our institution from 1/2010-12/2019 were identified. Patients with non-ovarian gynecologic malignancies were included. Patients undergoing palliative exenteration were included for perioperative outcomes but excluded from the survival analysis. Post-operative complications were defined as early (≤30 days) and delayed (31-180 days). Complications were graded using a validated institutional secondary surgical events system. Major complications were defined as Grade 3 or above which would, at minimum, require surgical, endoscopic, or radiological intervention. Appropriate statistical analyses were performed. Results: One-hundred patients were identified. Eighty-nine (89%) received treatment for recurrent disease, 5 (5%) for primary disease, 1 (1%) for persistent disease, and 5 (5%) received palliative treatment. The most common cancer type was cervical (n=30, 30%), followed by vulvar (n=27, 27%), uterine (n=24, 24%), and vaginal (n=19, 19%). The most common histologies were squamous cell carcinoma (n=61, 61%), endometrioid carcinoma (n=18, 18%), and adenocarcinoma (n=13, 13%). Sixty-two (62%) patients had total exenteration, 30 (30%) anterior exenteration, 8 (8%) posterior exenteration. The median age at time of surgery was 61.3 years (range, 28-86 years). There were no intraoperative deaths or deaths within 30 days of surgery. Six patients expired within the delayed time frame, including 1 (16.7%) from respiratory failure and 5 (83.3%) from aggressive progression of disease. Ninety-seven (97%) patients experienced a perioperative complication: 49 (50%) early, 1 (1%) delayed, 47 (48%) both early and delayed. Fifty/100 patients (50%) had a major complication: 22/50 (44%) early, 19/50 (38%) delayed, 9/50 (18%) both early and delayed. We did not identify any variables statistically associated with the development of a complication, including exenteration type, initial malignancy type, conduit type, operative time, estimated blood loss, or tumor volume. The median follow-up time for the entire cohort was 27.6 months (range, 1.0-117.5). The median follow-up time for survivors was 38.0 months (range, 1.0-117.5). The 3-year PFS was 61.0%, and the 3-year OS was 61.6%. There are 58 total survivors (58%), of whom 16 (28%) and 4 (7%) remain alive after 5 and 10 years, respectively. Conclusions: The complication rate for pelvic exenteration remains high, although we identified no variables showing association with the development of a complication. However, the lack of perioperative mortality, and improved oncologic outcomes, exemplify the advancements of this surgical approach since its inception.

Purpose: The AUA (American Urological Association) QIPS (Quality Improvement and Patient Safety) committee created a white paper on the diagnosis and management of nonneurogenic chronic urinary retention.Materials and Methods: Recommendations for the white paper were based on a review of the literature and consensus expert opinion from the workgroup.Results: The workgroup defined nonneurogenic chronic urinary retention as an elevated post-void residual of greater than 300 mL that persisted for at least 6 months and documented on 2 or more separate occasions. It is proposed that chronic urinary retention should be categorized by risk (high vs low) and symptomatology (symptomatic versus asymptomatic). High risk chronic urinary retention was defined as hydronephrosis on imaging, stage 3 chronic kidney disease or recurrent culture proven urinary tract infection or urosepsis. Symptomatic chronic urinary retention was defined as subjectively moderate to severe urinary symptoms impacting quality of life and/or a...

ContextMembranous urethral length (MUL) measured prior to radical prostatectomy (RP) has been identified as a factor that is associated with the recovery of continence following surgery.ObjectiveTo undertake a systematic review and meta-analysis of all studies reporting the effect of MUL on the recovery of continence following RP.Evidence acquisitionA comprehensive search of PubMed, EMBASE, and Scopus databases up to September 2015 was performed. Thirteen studies comprising one randomized controlled trial and 12 cohort studies were selected for inclusion.Evidence synthesisFour studies (1738 patients) that reported hazard ratio results. Every extra millimeter (mm) of MUL was associated with a faster return to continence (hazard ratio: 1.05; 95% confidence interval [CI]: 1.02–1.08, p

Objectives The aim of this study was to investigate surgical practice patterns of American urologists treating refractory overactive bladder (OAB) over the past decade. Refractory OAB remains a management challenge to urologists. When multiple medical therapies have failed, treatment options may include sacral neuromodulation (SNM) or surgery such as augmentation cystoplasty (AC). Methods Data on SNM and AC performed between 2003 and 2012 by certifying and recertifying urologists were obtained in the form of annualized case logs from the American Board of Urology (ABU). Associations between surgeon characteristics (type of certification, annual volume, practice type, and location) and these procedures were evaluated. Results Over the past decade, 756 of 6355 urologists certified with the ABU performed SNM or AC for the treatment of refractory OAB. Forty-five (6%) of these surgeons completed fellowships in female urology and 71 surgeons (9%) completed another type of fellowship program. Surgeons recertifying with ABU performed 76% of all SNM procedures. Although SNM and AC have increased from 64 to 2086 between 2003 and 2012, however, this is mainly driven by the increase of SNM from 48 to 2068 cases. Rates of AC have remained stable with 14 to 38 cases reported annually. However, they have declined relative to the total, from 25% in 2003 to less than 1% in 2012. Conclusions Sacral neuromodulation has increased dramatically over the past decade in surgeons certified with the ABU. This is in contrast to AC, which while remaining stable in number of procedures.

Male stress urinary incontinence is a common malady, most often caused by treatment of prostate cancer. After standard evaluation and confirmation of male stress urinary incontinence, multiple treatment options are available. Pelvic floor muscle exercises/therapy should be made available to all patients and if patient remain bothered with stress urinary incontinence, surgical therapy is an option. Surgical options include urethral bulking agents, male slings, and artificial urinary sphincters – all of which have varying degrees of efficacy, durability, and complication profile. Furthermore, some patients may be better candidates for a specific procedure due to known risk factors such as degree of incontinence of history of radiation therapy. Finally, secondary surgery is also available for patients who have already been treated surgically for male stress urinary incontinence. This manuscript will provide an overview of surgical treatment for male stress urinary incontinence.

Open prostatectomy and transurethral resection of the prostate (TURP) has been the gold standard therapy for moderate to severe lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). In recent years, laser vaporization technologies have now been recognized by international guidelines as an effective treatment alternative to TURP for treating BPH.In this contemporary review, we aim to discuss the application, outcomes and safety of photoselective vaporization of the prostate (PVP), specifically with the GreenLight laser. We also discuss the properties and evolution of the GreenLight laser as understanding the basic principles of this laser system.GreenLight PVP is a durable and effective alternative to TURP, especially in high-risk patients on systemic anticoagulation. Aside from providing similar efficacy and safety, the GreenLight PVP also allows for decreased hospitalization times, catheterization times and subsequently decreased healthcare costs. The latest generation laser, 180W XPS system, is found to be more cost-effective and efficacious in tissue vaporization when compared to previous laser generations.Laser vaporization is a safe and effective option to treating LUTS secondary to BPH. A patient-centered approach considering patient preference and preoperative parameters should be employed to determine the ideal treatment option for each individual patient.

e17006 Background: Padeliporfin (WST11) vascular-targeted photodynamic therapy (VTP) has shown significant clinical benefit as a localized partial gland ablation (PGA) therapy when compared to active surveillance for low-risk prostate cancer, by curbing progression and the need for radical treatment, leading to its regulatory approval in Europe. This phase 2b trial prospectively investigated WST11-VTP for intermediate-risk cancers. Methods: Men with unilateral Grade Group 2 (GG2) cancers (Gleason 3+4), evaluated with MRI and ultrasound-guided (TRUS) biopsy, underwent up to two WST11-VTP PGA sessions. Eligibility criteria included

Context Radical prostatectomy is the most common reason for male stress urinary incontinence. There is still uncertainty about its diagnostic and therapeutic management. Objective To evaluate current evidence regarding the diagnosis and therapy of postprostatectomy incontinence (PPI). Evidence acquisition A systematic review of the literature was performed in October 2015 using the Medline database. Evidence synthesis Diagnosis and conservative treatment of PPI are currently mostly based on expert opinions. Pelvic floor muscle training is the noninvasive treatment of choice of PPI. For invasive management of moderate to severe PPI, the artificial urinary sphincter is still the treatment of choice, but an increasing number of adjustable and nonadjustable, noncompressive as well as compressive devices are used more frequently. However, no randomized controlled trial has yet investigated the outcome of one specific surgical treatment or compared the outcome of different surgical treatment options. Conclusions The level of evidence addressing the surgical management of PPI is still unsatisfactory. Further research is urgently needed. Patient summary Incontinence after the removal of the prostate (postprostatectomy incontinence) is the most common cause of male stress urinary incontinence. First-line therapy is physiotherapy and lifestyle changes. If no satisfactory improvement is obtained, various surgical treatment options are available. The most commonly used is the artificial urinary sphincter, but other treatment options like male slings are also available.

The convective heat transfer coefficient was measured experimentally using a controlled one-dimensional (1-D) frying methodology. Hollow Teflon disc was used as a sample holder. Thermostable silicon glue was used to seal the sample in the Teflon disc. This insulated the edges of the potato disc from the frying oil thus restricting oil penetration from only the exposed top and bottom surfaces. This rendered this set of frying experiments a 1-D frying process. The peak heat transfer coefficient values were determined to be 3617, 4517 and 7307 W/m 2 °C at frying temperatures of 150, 170 and 190 °C, respectively. The heat transfer coefficient reached its peak value towards the end of frying at all temperatures.