Pilot study to assess the feasibility of self-administered, low-dose methoxyflurane for cystoscopic procedures.

INTRODUCTION: Methoxyflurane (MEOF) (Penthrox™) is an inhaled, self-administered, non-opioid analgesic approved by Health Canada for the short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures. In this pilot study, we evaluated the feasibility of using MEOF as an anesthetic agent in 11 patients undergoing outpatient cystoscopic procedures. METHODS: The average duration of the procedure was 24 (range 20-35) minutes and this included 10 minutes of administration time of the drug and five minutes of wait time before the procedure. The average monitoring time from start to end of the procedure was 23 (range 20-35) minutes and this included 15 minutes of monitoring post-procedure. On a scale of 0-10, patients on average rated the pain 4/10 (standard deviation [SD] 2.6). RESULTS: Global performance was on average 3/4 (SD 1.3) for the patients and 3/4 (SD 1.1) for the operator. Of the 11 patients, four reported adverse events; two experienced euphoria, one experienced dizziness, and one was unable to tolerate the medication. Two patients noted their adverse events to be of moderate intensity, while the other two were of mild intensity. None of the adverse events was deemed serious. CONCLUSIONS: Our findings in this pilot study provide proof of principle for the design of a randomized control trial to evaluate MEOF as an anesthetic in an outpatient cystoscopic procedural setting. As more urologic procedures are being performed in an outpatient setting, this may offer significant clinical benefit.

Prevalence and repair patterns of vesicovaginal fistula: a large retrospective population-based cohort analysis.

PURPOSE: Vesicovaginal fistulae (VVF) have a significant negative impact on quality of life, with failed surgical repair resulting in ongoing morbidity. Our aim was to characterize the rate of VVF repair and repair failures over time, and to identify predictors of repair failure. METHODS: We completed a population-based, retrospective cohort study of all women who underwent VVF repair in Ontario, Canada, aged 18 and older between 2005 and 2018. Risk factors for repair failure were identified using multivariable cox proportional hazard analysis; interrupted time series analysis was used to determine change in VVF repair rate over time. RESULTS: 814 patients underwent VVF repair. Of these, 117 required a second repair (14%). Mean age at surgery was 52 years (SD 15). Most patients had undergone prior gynecological surgery (68%), and 76% were due to iatrogenic injury. Most repairs were performed by urologists (60%). Predictors of VVF re-repair included iatrogenic injury etiology (HR 2.1, 95% CI 1.3-3.45, p = 0.009), and endoscopic repair (HR 6.1, 95% CI 3.1-11.1, p < 0.05,); protective factors included combined intra-abdominal/trans-vaginal repair (HR 0.51, 95% CI 0.3-0.8, p = 0.009), and surgeon years in practice (21 + years-HR 0.5, 95% CI 0.3-0.9, p = 0.005). Age adjusted annual rate of VVF repair (ranging from 0.8 to 1.58 per 100,000 women) and re-repair did not change over time. CONCLUSIONS: VVF repair and re-repair rates remained constant between 2005 and 2018. Iatrogenic injury and endoscopic repair predicted repair failure; combined intra-abdominal/trans-vaginal repair, and surgeon years in practice were protective. This suggests surgeon experience may protect against VVF repair failure.

Safety and efficacy of an α1 -blocker plus mirabegron compared with an α1 -blocker plus antimuscarinic in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and overactive bladder: A systematic review and network meta-analysis.

AIM: Antimuscarinics and the ß3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α1 -adrenoreceptor antagonists (α1 -blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an α1 -blocker plus mirabegron with an α1 -blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations. METHODS: Included records had to be from a parallel-group, randomized clinical trial that was ≥8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an α1 -blocker plus OAB agent with an α1 -blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Qmax ). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis. RESULTS: Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the α1 -blocker plus mirabegron and α1 -blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the α1 -blocker plus mirabegron group compared with the α1 -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Qmax . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α1 -blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation. CONCLUSION: This systematic review and meta-analysis showed that an α1 -blocker plus mirabegron and an α1 -blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting.

Healthcare utilization during transition to adult care in patients with spina bifida A population-based, longitudinal study in Ontario, Canada.

INTRODUCTION: Individuals with spina bifida (SB) may experience negative health outcomes because of an informal transition from pediatric to adult care that results in using the emergency room (ER ) for non-acute health problems. METHODS: We conducted a retrospective, population-based cohort study of all people with SB in Ontario, Canada turning 18 years old between 2002 and 2011. These patients were followed for five years before and after age 18. Primary outcome was the annual rate of ER visits. Secondary outcomes included rates of hospitalization, surgery, primary care, and specialist outpatient care. We estimated the association between age and primary and secondary outcomes using negative binomial growth curve models, adjusting for patient-level baseline covariates. RESULTS: Among the 1215 individuals with SB, there was no trend of ER visits seen with increasing age (relative risk [RR ] 0.99, 95% confidence interval [CI] 0.98-1.02); however, there was a significant increase in the rate of ER visits associated with turning 18 years (RR 1.14, 95% CI 1.03-1.27). Turning 18 years old was also associated with a decreased rate of hospital admissions (RR 0.79, 95% CI 0.66-0.95) and no change in surgeries (RR 0.80, 95% CI 0.64-1.02). Visits to primary care physicians remained stable over the same period (RR 0.96, 95% CI 0.90-1.01), while visits to SB-focused specialists decreased after age 18 (RR 0.81, 95% CI 0.75-0.87). CONCLUSIONS: In patients with SB, the rate of ER visits increased significantly at 18 years old, while hospital admissions and specialist physician visits decreased at the same time. Models of transitional care can aim to reduce non-urgent ER visits and facilitate regular specialist care.

Prevalence and Natural History of Non-metastatic Castrate Resistant Prostate Cancer: A Population-Based Analysis.

PURPOSE: To determine the prevalence and natural history of nmCRPC prior to the adoption of novel androgen receptor axis-targeting therapies(ARAT). MATERIALS AND METHODS: This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada between January 2007-March 2018. Patients with prostate cancer, castrate level of testosterone(<1.7nmol/L) and a PSA>2.0ng/mL with a subsequent rise>25% from the nadir, and without metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and all-cause death are presented as medians with interquartile range(IQR). Predictors of time from nmCRPC to death were compared using univariable and multivariable cox proportional hazard models. RESULTS: We identified 2045 patients with nmCRPC. Median age was 79(IQR:72-84). 984 patients(48.1%) received upfront hormonal therapy while 583(28.5%) received initial radiotherapy and 478(23.4%) underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years(IQR:3-10). The average annual prevalence of nmCRPC was 8% among men receiving ADT. Crude median time from nmCRPC to death was 37.6 months(IQR:22.1-55.4). Median time from nmCRPC to metastasis and metastasis to death was 20.0 and 8.3 months, respectively. Patients who had primary surgery experienced longer crude survival. Older patients, patients who had a higher PSA at nmCRPC, and patients with grade group 4 to 5 disease had a shorter time from nmCRPC to death. CONCLUSION: This is the largest population-level analysis of the prevalence and natural history of nmCRPC. The current study can be used as a historical cohort to compare how novel imaging modalities and ARAT impact prevalence and disease trajectory over time.

NIRS: Past, Present, and Future in Functional Urology.

Purpose of Review: Near infrared spectroscopy (NIRS) is a non-invasive optical technique that uses near infrared light to detect the oxygenation status and hemodynamics of various organs. This article reviews the use of NIRS for the non-invasive assessment of lower urinary tract dysfunction (LUTD). Applications include assessment of bladder outlet obstruction, overactive and underactive bladder, neurogenic LUTD, pediatric LUTD, interstitial cystitis/bladder pain syndrome, and pelvic floor dysfunction. In addition, the article describes how NIRS is elucidating more about the brain-bladder connection. Technological advancements enabling these applications are also discussed. Recent Findings: While evidence exists for the application of NIRS throughout a wide range of LUTD, most of these studies are limited by small sample sizes without matched controls. Investigators have experienced problems with reproducibility and motion artifacts contaminating the data. The literature is also becoming dated with use of older technology. Summary: NIRS holds potential for the non-invasive acquisition of urodynamic information over time scales and activities not previously accessible, but it is not yet ready for use in routine clinical practice. Advances in wearable technology will address some of the current limitations of NIRS, but to realize its full potential, larger scale validation studies will be required. Moreover, multidisciplinary collaboration between clinicians, scientists, engineers, and patient advocates will be critical to further optimize these systems.

Hemi-Kock Continent Stoma With Augmentation Cystoplasty: Modifications and Outcomes.

OBJECTIVE: To evaluate the long-term outcomes and impact of surgical modifications on the need for secondary surgery of the Hemi-Kock continent catheterizable stoma, comprising a detubularized ileal segment with an attached stapled ileoileal intussusception of the catheterizable channel, in patients with complex lower urinary tract disorders. The technique may be used for augmentation in patients with reduced bladder capacity who require a continent catheterizable channel. Compared to the flap and ileocecal valve procedures, the hemi-Kock technique has not been widely adopted. MATERIALS AND METHODS: This is a retrospective case series including all patients who underwent a hemi-Kock catheterizable channel with cystoplasty from a single institution. Surgical technique and modifications in valve construction and tapering of the catheterizable limb are described. RESULTS: A total of 109 patients, with a median age of 38 years (range 18-72), underwent the procedure. At a mean of 10.4 years, 98 patients (90%) reported that they were managing with clean intermittent catheterization ± pads; 11 (10%) were failures. A total of 70 (64.2%) patients underwent secondary interventions with >60% performed endoscopically or under local anesthesia, mainly for bladder stones. Fourteen patients (12.8%) required valve revisions. However, the rate decreased from 18.2% (8/44) to 9.3% (6/65) following incorporation of the surgical modifications. CONCLUSION: We present the largest cohort to date of patients managed with a Hemi-Kock catheterizable channel and cystoplasty. Valve revision rate improved with surgical modifications. We demonstrate long-term durability and maintenance of stomal catheterization in the vast majority of patients.

Morbidity and predictors of delayed recognition of iatrogenic ureteric injuries.

INTRODUCTION: Although intraoperative iatrogenic ureteric injuries (IUI) are rare, significant consequences can occur if they are unrecognized at the time. The focus of our study is to characterize the associated morbidity and identify predictors of delayed recognition of IUI. METHODS: Sunnybrook Health Sciences Centre Research Ethics Board approved the study. Patients with a diagnosis of IUI between 2002 and 2020 were identified through an institutional electronic medical record system. Data pertaining to the demographic characteristics, diagnosis, and management of IUI, as well as overall outcomes were collected retrospectively. RESULTS: Of the 103 patients identified, 83% were female, 52% had previous abdominal surgery, and 18% had previous radiation. The median age was 67 (range 21-88) years. Twenty percent were not recognized at the time of surgery. Although delayed recognition was not a significant predictor for poor outcome after subsequent repair (i.e., hydronephrosis, ureteric stricture/obstruction), it was associated with substantial morbidity to the patient (i.e., additional procedures) and increased cost to the healthcare system (i.e., longer hospital stay, re-admission to hospital). Patients who underwent laparoscopic surgery had an 11 times more likely chance of having an unrecognized IUI as compared to those who underwent open surgery (odds ratio 11.515, p=0.0001). CONCLUSIONS: Delayed recognition of IUI may be associated with considerable adverse effects. In this retrospective case series, we identified laparoscopic surgery as a significant predictor for delayed recognition of IUI. This information underscores the need for future studies to facilitate intraoperative identification of ureteric injuries, particularly during laparoscopic procedures.

Association between chronic bladder catheterisation and bladder cancer incidence and mortality: a population-based retrospective cohort study in Ontario, Canada.

OBJECTIVES: To compare the risk of bladder cancer and bladder cancer mortality among patients with chronic bladder catheterisation (indwelling or intermittent) to patients from the general population. DESIGN: Retrospective cohort study. SETTING: Population-based study in Ontario, Canada between 2003 and 2018. PARTICIPANTS: Adult patients 18-90 years of age with chronic bladder catheterisation were hard matched to patients from the general population without a history of bladder catheterisation. INTERVENTIONS: The presence of a chronic catheter was defined as a minimum of two physician encounters for bladder catheterisation, suprapubic tube insertion or home care for catheter care separated by at least 28 days. Urinary tract infection (UTI) rates were collected. MAIN OUTCOME MEASURES: Bladder cancer and bladder cancer-specific mortality after a 1-year lag period were compared between groups. RESULTS: We identified 36 903 patients with chronic catheterisation matched to 110 709 patients without a history of catheterisation. Patients were followed for a median of 8.8 years (IQR: 5.2-11.9 years). The median age was 62 years (IQR: 50-71) and 52% were female. More patients in the catheter group developed bladder cancer (393 (1.1%) vs 304 (0.3%),p<0.001). There were 106 (0.3%) bladder cancer deaths in the catheter group and 59 (0.1%) in the comparison group (p<0.001). Chronic catheterisation (adjusted subdistribution HR (sdHR)=4.80, 95% CI: 4.26 to 5.42,p<0.001) and the number of UTIs (adjusted sdHR=1.04 per UTI, 95% CI: 1.04 to 1.05,p<0.001) were independent predictors of bladder cancer. The relative rate of bladder cancer-specific death was more than eightfold higher among patients with chronic catheterisation (adjusted sdHR=8.68, 95% CI: 6.97 to 10.81,p<0.001). Subgroup analysis among patients with neurogenic bladder and bladder calculi similarly revealed an increased risk of bladder cancer diagnosis and mortality. Bladder cancer risk was highest among patients in the two longest catheter duration quintiles (2.9-5.9 and 5.9-15.5 years). CONCLUSIONS: This is the first study to quantify the increase in bladder cancer incidence and mortality in a large, diverse cohort of patients with chronic indwelling or intermittent bladder catheterisation. The risk was highest among patients with a chronic catheter beyond 2.9 years.

Management of high-grade renal traumas with collecting system injuries.

INTRODUCTION: Approximately 50% of all high-grade renal traumas (HGRT, American Association for the Surgery of Trauma [AAST] grade 4/5) have associated collecting system injuries. Although most of these collecting system injuries will heal spontaneously, approximately 20-30% of these injuries are managed with ureteric stents. The objective of the study was to review the management of HGRT with collecting system injuries in a level 1 trauma center. METHODS: This was a single-center, retrospective cohort study of trauma patients with HGRT and collecting system injuries from 1998-2019. RESULTS: We identified 147 patients with HGRT. Of the 105 patients who had trauma computed tomography (CT) imaging within 24 hours, 46 were found to have collecting system injuries. Seven of these patients underwent intervention based on initial CT findings; the remaining 39 patients with urinary extravasation were conservatively managed. Of the 37 patients who underwent reimaging, 22 (59%) demonstrated a stable or resolving collection and 15 (41%) demonstrated continued urinary extravasation. Resolution of extravasation on subsequent imaging was observed in 10 of those patients, while five patients (14%) required intervention (four stents, one percutaneous drain) for symptoms/signs of urinary extravasation. CONCLUSIONS: In this study, most patients with HGRT and collecting system injuries did not require intervention unless the patient became symptomatic. The majority of collecting system injuries resolved with no intervention. This study underscores the need for future prospective trials to investigate the necessity of intervening in HGRT collecting system injuries and, secondarily, the need for routine re-imaging in these asymptomatic patients.

Stress Incontinence Surgery Does Not Cause Pelvic Malignancy: A Population-Based Cohort Study.

PURPOSE: We sought to determine if stress urinary incontinence surgery (mesh or nonmesh) is associated with the development of pelvic malignancies later in life. MATERIALS AND METHODS: We performed a retrospective cohort study between January 1, 2002 and October 31, 2015 of all women in Ontario, Canada without a history of pelvic malignancy who underwent an index stress incontinence surgery. The primary outcome was a composite of any pelvic malignancy (including urological and gynecological cancers) following stress incontinence surgery. Secondarily, we considered each cancer individually. A survival analysis using a Cox proportional-hazards model with a 3-level categorical exposure (mesh surgery, nonmesh surgery, and control) was performed. Patients were followed until death, emigration or the study end (October 31, 2017). RESULTS: Of the women 74,968 underwent stress urinary incontinence surgery during the study period. There were 5,505,576 women in the control group. Over a median followup of 8.5 years (IQR, 5.5-11.9), 587 pelvic malignancies occurred in the surgery group. Women who underwent stress incontinence surgery had a reduced risk of pelvic malignancy independent of surgery type, compared to controls (Wald type 3 p <0.001; mesh HR, 0.68 [95% CI, 0.62-0.76]; p <0.0001; nonmesh HR, 0.37 [95% CI, 0.29-0.46]; p <0.0001). The individual pelvic cancers similarly demonstrated a reduced risk of malignancy following stress incontinence surgery. CONCLUSIONS: At a median followup of 8.5 years, women had no increased risk of pelvic malignancy following either mesh or nonmesh stress urinary incontinence surgery in a large population-based cohort.

Comprehensive assessment of the morbidity of renal mass biopsy: A population-based assessment of biopsy-related complications.

INTRODUCTION: We sought to assess seven-day and 30-day complications following renal mass biopsy (RMB), including mortality, hospitalizations, emergency department (ED) visits, and operative and non-operative complications and compare these to rates in population-matched controls. METHODS: We performed a population-based, matched, retrospective cohort study of patients undergoing RMB following consultation with a urologist and axial imaging from 2003-2015 in Ontario, Canada. Data on seven-day and 30-day rates of mortality, as well as operative and non operative complications after RMB were reported. The seven-day and 30-day rates of mortality, operative and non-operative interventions, hospitalizations, and ED visits were compared to matched controls using multivariable logistic regression. RESULTS: Among 6840 patients who underwent RMB in the study period, 24 (0.4%) and 159 (2.3%) died within seven and 30 days of their biopsy, respectively. Seven- and 30-day operative intervention rates were 79 (1.2%) and 236 (3.4%), respectively. Seven- and 30-day non-operative intervention rates were 227 (3.3%) and 529 (7.7%), respectively. Thirty-day mortality (odds ratio [OR] 8.1, 95% confidence interval [CI] 5.1-13.0), hospitalizations (OR 12.6, 95% CI 10.6-15.2), and ED visits (OR 3.8, 95% CI 3.4-4.3) were more common among patients who underwent RMB than the matched controls (p<0.001 for each). CONCLUSIONS: Patients undergoing RMB may have a small but non-negligible increased risk of mortality, hospital readmission, and ED visits compared to matched controls. However, limitations in the granularity of the dataset limits the strength of these conclusions. Further studies are needed to confirm our results. These risks should be discussed with patients for shared decision-making and considered in the risk/benefit tradeoff for the management of small renal masses.

Mirabegron Vs Placebo Add-on Therapy in Men With Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Safety Analysis From the Randomized, Phase 4 PLUS Study.

OBJECTIVE: To analyze the safety of mirabegron add-on therapy in men with overactive bladder symptoms concurrently receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia. METHODS: The Phase 4 PLUS study comprised a 4-week run-in period (tamsulosin [0.4 mg]) and a 12-week randomized treatment period (add-on treatment: mirabegron [25 mg] or placebo). Doses were increased to mirabegron 50 mg or matched placebo after 4 weeks. Safety assessments: treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiograms, and changes in postvoid residual volume and maximum urinary flow (Qmax). RESULTS: The safety analysis set included 352 tamsulosin plus mirabegron (TAM + MIRA) and 354 tamsulosin plus placebo (TAM + PL) patients. The frequency of overall TEAEs was higher with TAM + PL, although a higher incidence of drug-related TEAEs was observed with TAM + MIRA. Most TEAEs were mild or moderate in severity. Drug-related serious TEAEs were reported for 3 patients (2 TAM + MIRA patients: acute myocardial infarction with cerebral infarction and angina pectoris, 1 TAM + PL patient: lacunar stroke). Hypertension, headache, and nasopharyngitis were the most common TEAEs. Special interest TEAEs were infrequently reported. The most common was urinary retention and 2 TAM + MIRA patients required catheterization (neither led to discontinuation). No major changes in blood pressure or pulse rate were noted and similar electrocardiogram parameters were observed for both groups. Changes in mean postvoid residual volume and Qmax were not clinically meaningful. CONCLUSION: No unexpected safety concerns were noted in men receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia who subsequently received mirabegron add-on therapy.

Triamcinolone acetonide injections for the treatment of recalcitrant post-radical prostatectomy vesicourethral anastomotic stenosis: A retrospective look at efficacy and safety.

INTRODUCTION: We aimed to evaluate the success of bladder neck injections of triamcinolone at the time of transurethral bladder neck incision (BNI) for prevention of recurrent vesicourethral anastomotic stenosis (VUAS) following prostate cancer treatment. METHODS: This is a retrospective cohort study examining patients with recurrent VUAS post-radical prostatectomy (RP) ± radiation treated with triamcinolone injections at the time of BNI. VUAS was diagnosed by symptoms followed by cystoscopy or urethrography. The outpatient procedures were done under general anesthesia. Cold knife incisions were made at the three, nine, and 12 o'clock BN positions, followed by triamcinolone injections (4 mg/mL) into the three and nine o'clock incision sites. Treatment outcomes were determined with cystoscopy. RESULTS: Eighteen men underwent 25 procedures over a four-year period. Median age at diagnosis of VUAS was 65 (interquartile range [IQR] 61-68); median time to VUAS from RP was eight months (IQR 5-12). Fourteen patients (78%) had radiation treatment. The cohort had 128 unsuccessful VUAS treatments, with a median of five failed treatments per patient (IQR 3-10). Failed treatments included BN dilation, BNI, BN injection of mitomycin C, and urethral stent placement. Success rate after a mean of 16.3 months (standard deviation [SD] 8.1) from the time of triamcinolone injection was 83% (15/18). Six patients went on to have successful incontinence surgery. Five patients (28%) had treatment complications (bleeding, urinary tract infection, pain, and urinary extravasation). The three non-responders are stable and awaiting re-treatment with triamcinolone injection. CONCLUSIONS: Triamcinolone bladder neck injections for post-RP VUAS are a useful and safe treatment for recurrent stenosis.

Multicentered Assessment of Clinical Outcomes and Factors Associated With Failure of the Adjustable TransObturator Male System (ATOMS).

OBJECTIVE: To assess postoperative outcomes from the Adjustable TransObturator Male System (ATOMS) and identify factors influencing failure to achieve continence. PATIENTS AND METHODS: A multicentered analysis was performed on all patients treated for postprostatectomy incontinence using the third-generation ATOMS at 9 Canadian tertiary referral centers. The primary outcome was continence (defined as requiring ≤1 pad postoperatively for patients requiring ≥2 pads preoperatively and 0 pads for those requiring 1 pad preoperatively). Secondary outcomes included improvement (>50% change in pad use), patient satisfaction, explantation, and postoperative complications. RESULTS: Two hundred and eighty nine patients with a mean age of 68.9 years were analyzed. Pre-operatively mean pad per day use was 4.2 (1-12), 31.5% of patients reported severe incontinence (≥5 pads/day), 33.9% had concurrent radiotherapy and 19.4% had failed previous incontinence surgery. Overall continence rate was 73.3% (n = 212) at a mean follow-up of 19.6 months. More than eighty nine percent (89.3%) (n = 258) of patients experienced >50% improvement, 84.4% (n = 244) of patients were satisfied with the results of surgery. More than seven percent (7.9%) (n = 23) required device explantation. On multivariate Cox regression analysis, concurrent radiotherapy (hazard ratio [H.R.] 2.3, P < .001), diabetes (H.R. 2.2, P = .007) and increased pre-operative pad usage (H.R. 1.1, P = .02) were each associated with failure to achieve continence, while patient age (P = .60), obesity (P = .08), prior urethral stenosis (P = .56), and prior incontinence surgery (P = .13) were not. Radiation therapy was also associated with device explantation (H.R. 2.7, P = .02). CONCLUSION: ATOMS is a safe and efficacious for treatment of postprostatectomy incontinence. However, patients with prior radiation, increased pre-operative pad use, or diabetes are less likely to achieve continence.

Urethrovaginal fistula repair with or without concurrent fascial sling placement: A retrospective review.

INTRODUCTION: We sought to review outcomes of urethrovaginal fistula (UVF) repair, with or without concurrent fascial sling placement. METHODS: All patients diagnosed with UVF at our center from 1988-2017 were included in this study. Patient charts were reviewed from a prospectively kept fistula database, and patient characteristics and surgical outcomes were described. Descriptive statistics were applied to compare complication rates between patients with or without fascial sling placement at the time of UVF repair. RESULTS: A total of 41 cases of UVF were identified, all of which underwent surgical repair. Median age at diagnosis was 49 years (interquartile range [IQR] 35-62). All patients had undergone pelvic surgery. UVF etiology was secondary to stress urinary incontinence (SUI) surgery in 17 patients (41%) and urethral diverticulum repair in seven patients (17%). The most common presenting symptom was continuous incontinence in 19 patients (46%). Nineteen patients had a fascial sling placed at the time of surgery (46%), with no significant difference in complication rates (26% vs. 23%, p=0.79). Two patients had Clavien-Dindo grade I complications (5%) and one had a grade III complication (2%). Four patients had long-term complications (10%), including urinary retention, chronic pain, and urethral stricture. Two patients had UVF recurrence (5%). Median followup after surgery was 21 months (IQR 4-72). CONCLUSIONS: UVF should be suspected in patients with continuous incontinence following a surgical procedure. Most UVF surgical repairs are successful and can be done with concurrent placement of a fascial sling.

Assessment of Secondary Sarcomas Among Patients With Cancer of the Abdomen or Pelvis Who Received Combinations of Surgery, Radiation, and Chemotherapy vs Surgery Alone.

Importance: The association of radiation and chemotherapy with the development of secondary sarcoma is known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis. Objective: To compare the risk of secondary sarcoma among patients treated with combinations of surgery, radiation, or chemotherapy with patients treated with surgery alone and the general population. Design, Setting, and Participants: This population-based cohort study included 173 580 patients in Ontario, Canada, with nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis. Patients were enrolled from January 1, 2002, to January 31, 2017. Data analysis was conducted from March 1, 2019, to January 31, 2020. Exposures: Treatment combinations of radiation, chemotherapy, and surgery. Main Outcome and Measures: Diagnosis of sarcoma based on histologic codes from the Ontario Cancer Registry. Time to sarcoma was compared using a cause-specific proportional hazard model. Results: Of 173 580 patients, most were men (125 080 [72.1%]), and the largest group was aged between 60 and 69 years (58 346 [33.6%]). Most patients had genitourinary cancer (86 235 [51.4%]) or colorectal cancer (69 241 [39.9%]). Overall, 64 301 (37.1%) received surgery alone, 51 220 (29.5%) received radiation alone, 15 624 (9.0%) were treated with radiation and chemotherapy, 15 252 (8.8%) received radiation with surgery, and 11 822 (6.8%) received all 3 treatments. A total of 332 patients (0.2%) had sarcomas develop during a median (interquartile range) follow-up of 5.7 (2.2-8.9) years. The incidence of sarcoma was 0.3% among those who underwent radiation alone (138 of 51 220) and radiation with chemotherapy (40 of 15 624), 0.2% among those who received radiation and surgery (36 of 15 252) and all 3 modalities (25 of 11 822), and 0.1% among those who received surgery with chemotherapy (13 of 14 861) and surgery alone (80 of 64 801). Compared with a reference group of patients who had surgery alone, the greatest risk of sarcoma was found among patients who underwent a combination of radiation and chemotherapy (cause-specific relative hazard [csRH], 4.07; 95% CI, 2.75-6.01; P < .001), followed by patients who had radiation alone (csRH, 2.35; 95% CI, 1.77-3.12; P < .001), radiation with surgery (csRH, 2.33; 95% CI, 1.57-3.46; P < .001), and all 3 modalities (csRH, 2.27; 95% CI, 1.44-3.58; P < .001). In the general population, 7987 events occurred during 46 554 803 person-years (17.2 events per 100 000 person-years). The standardized incidence ratio for sarcoma among patients treated with radiation compared with the general population was 2.41 (95% CI, 1.57-3.69; 41.3 events per 100 000 person-years). The annual number of cases of sarcoma increased from 2009 (15 per 100 000 persons) to 2016 (32 per 100 000 persons), but the annual rate did not change during the study period. Conclusions and Relevance: In this cohort study, patients treated with radiation or chemotherapy for abdominopelvic cancers had an increased rate of sarcoma. Although the absolute rate is low, patients and physicians should be aware of this increased risk of developing sarcoma.

Rates of primary and secondary treatments for patients on active surveillance for localized prostate cancer-A population-based cohort study.

BACKGROUND: The rate of primary and secondary treatment while on active surveillance (AS) for localized prostate cancer at the general population level is unknown. Our objective was to determine the patterns of secondary treatments after primary surgery or radiation for patients who undergo AS. METHODS: This was a population-based retrospective cohort study of men aged 50-80 years old in Ontario, Canada, between 2008 and 2016. We identified 26 742 patients with prostate cancer, a Gleason grade score ≤7, and an index prostate-specific antigen ≤10 ng/mL. Patients were categorized as undergoing AS with or without delayed primary treatment (DT; treatment >6 months after diagnosis) versus immediate treatment (IT; treatment ≤6 months). Patients receiving DT and IT were propensity score matched and the rate of secondary treatment (surgery or radiation ± androgen deprivation treatment) was compared using Cox proportional hazards models. RESULTS: We identified 10 214 patients who underwent AS and 11 884 patients who underwent IT. Among patients undergoing AS, 3724 (36.5%) eventually underwent DT and among them, 406 (10.9%) underwent secondary treatment. The median time to DT was 1.2 years (IQR 0.5-8.1 years). The relative rate of undergoing secondary treatment was similar in the DT vs IT group (HR 0.92; 95% CI: 0.79-1.08). The risk of death in the DT group was higher compared to patients who did not undergo treatment (HR 1.23, 95% CI: 1.01-1.49). CONCLUSIONS: Among patients with localized prostate cancer on AS, one third undergo DT. The rate of secondary treatment was similar between the DT and IT groups. Patients in the DT group may experience a higher risk of mortality compared to those who remained on AS.

Surgical management of benign prostatic obstruction: 20-year population-level trends.

INTRODUCTION: Benign prostatic obstruction (BPO) due to histological benign prostatic hyperplasia is highly prevalent among older men. Despite widespread use of medical therapy, surgical treatment remains a mainstay in the management of BPO. We sought to characterize trends in the surgical management of BPO in Ontario, Canada. METHODS: We performed an interrupted time-series analysis using segmented regression among men aged 18 years and older undergoing surgical treatment for BPO between January 1, 1994 and December 31, 2014 in Ontario, Canada. The passage of time was considered the primary exposure. The primary outcome was the proportion of all BPO surgeries performed using each of the following modalities: transurethral resection of the prostate (TURP), endoscopic laser prostatectomy, open/laparoscopic prostatectomy, and others. RESULTS: We identified 136 459 men who underwent BPO surgery between 1994 and 2014. The annual age-adjusted rate of BPO surgery declined significantly over time (24 to 10 per 10 000 population in 1994 and 2014, respectively). From 1994-2001, there were no significant changes in the distribution of BPO surgical modalities, with TURP the most common throughout (97.2% and 97% in 1994 and 2001, respectively). From 2002-2014, there was a significant decline in the use of TURP (92.1% to 76.9%; p=0.027) with a corresponding increase in the use of endoscopic laser prostatectomy (3.5% to 21.9%; p=0.0008). CONCLUSIONS: This study demonstrates a shift in the management of BPO, with increasing use of endoscopic laser prostatectomy, beginning in 2002. However, TURP remains the most common treatment modality.

Efficacy and Safety of Mirabegron versus Placebo Add-On Therapy in Men with Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Randomized, Phase 4 Study (PLUS).

PURPOSE: PLUS investigated the efficacy and safety of mirabegron add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying lower urinary tract symptoms attributable to benign prostatic hyperplasia. MATERIALS AND METHODS: In this phase 4 study a 4-week 0.4 mg tamsulosin run-in period was followed by a 12-week, randomized, double-blind, treatment period in which patients initially received 25 mg mirabegron or placebo add-on therapy. At 4 weeks doses were titrated to 50 mg mirabegron or placebo equivalent. Efficacy end points were changes from baseline to end of treatment in mean number of micturitions per day (primary), mean volume voided per micturition, number of urgency episodes per day, total urgency and frequency score, and total International Prostate Symptom Score (secondary). Safety assessments included treatment emergent adverse events, and post-void residual volume, and maximum urinary flow measurements. RESULTS: Of the 676 men most were 65 years old or older (380, 56.2%). Tamsulosin plus mirabegron was statistically superior to tamsulosin plus placebo in reducing the mean number of micturitions per day (-2.00 vs -1.62; adjusted difference -0.39; 95% CI -0.76, -0.02). Statistically superior results were noted for tamsulosin plus mirabegron in mean volume voided per micturition, urgency episodes per day, and total urgency and frequency score (not International Prostate Symptom Score). Higher overall treatment emergent adverse event rates were observed with tamsulosin plus placebo, although higher rates of drug related treatment emergent adverse events were noted with tamsulosin plus mirabegron. Urinary retention rates were higher in the tamsulosin plus mirabegron group. Post-void residual volume and maximum urinary flow results were not clinically meaningful. CONCLUSIONS: The results of PLUS underscore the utility of mirabegron add-on therapy to treat men with overactive bladder symptoms receiving tamsulosin for benign prostatic hyperplasia.