Feras Alhalabi

Cumulative number of altered biomarkers in mammalian target of rapamycin pathway is an independent predictor of outcome in patients with clear cell renal cell carcinoma.

OBJECTIVE To evaluate the association of the altered expression of the mammalian target of rapamycin (mTOR) pathway components with oncologic outcomes in patients with nonmetastatic clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS Immunohistochemistry for phosphorylated-S6, phosphorylated-mTOR, mTOR, phosphorylated-AKT, hypoxia inducible factor-1α, Raptor, phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and phosphorylated 4E-binding protein-1 was performed on tissue microarray constructs of patients treated for nonmetastatic kidney cancer from 1997 to 2010. The relationship between individual altered marker expression and a prognostic marker score (low, intermediate, and high, defined as ≤ 3, 4-5, >5 altered biomarkers, respectively) and oncologic outcome was assessed. RESULTS The study included 419 patients with nonmetastatic ccRCC, with a median follow-up period of 26 months (range 6-150). The tumors were nonorgan confined (pT3-T4) in 86 (20.5%) and high Fuhrman nuclear grade (3-4) in 131 (31%). A low, intermediate, and high prognostic marker score was found in 214 (51%), 152 (36%), and 53 (13%) patients, respectively. Kaplan-Meier analysis demonstrated a statistically significant correlation between the risk groups and disease recurrence and cancer-specific survival. In a multivariate Cox regression analysis controlling for tumor stage and grade, a high marker score was an independent predictor of disease recurrence (hazard ratio 3.3, 95% confidence interval 1.33-8.39, P = .01), and a combination of a high and an intermediate score was an independent predictor of survival (hazard ratio 4.8, 95% confidence interval 1.27-4.78, P = .008). CONCLUSION The cumulative number of aberrantly expressed biomarkers correlated with aggressive tumor biology and inferior oncologic outcomes in patients with ccRCC. Our data support prospective pathway-based exploration of the mTOR signaling cascade to augment current clinicopathologic predictors of oncologic outcomes in patients with ccRCC.

Distal intramural urethral pathology in women

PURPOSE We reviewed the evaluation of distal intramural urethral pathology in women and its management using urethral dilation and general anesthesia. MATERIALS AND METHODS After receiving institutional review board approval we reviewed consecutive charts of women who underwent urethral dilation under general anesthesia for distal intramural urethral pathology. The pathological condition was defined as bothersome lower urinary tract symptoms with distal urethral narrowing and proximal ballooning on lateral voiding cystourethrogram. Patients with extramural, intraluminal or nondistal urethral pathology or neurogenic bladder were excluded from study. Success was defined as complete or major lower urinary tract symptom improvement 6 months after 1 urethral dilation using general anesthesia and no need for a repeat or another procedure. RESULTS Eight of 101 cases (8%) reviewed between 1998 and 2010 were lost to followup at less than 6 months. Of the remaining 93 patients with a mean ± SD age of 52 ± 16 years and a mean followup of 46 ± 37 months 47 (51%) were classified as success. The failure group had a mean age of 50 ± 16 years and a mean time to failure of 8 ± 12 months. A history of urethral dilation was more common in the failure group (17% vs 39% cases, p = 0.02). CONCLUSIONS Urethral dilation using general anesthesia is effective in some women with distal intramural urethral pathology diagnosed after extensive evaluation, including imaging and urodynamics. Distal intramural urethral pathology is a rare entity and these results are not applicable to women with nonspecific lower urinary tract symptoms.

Management of Urinary Incontinence Following Suburethral Sling Removal

Purpose: We evaluated urinary incontinence outcomes following synthetic suburethral sling removal in women. Materials and Methods: We reviewed a prospectively maintained database of 360 consecutive women who underwent transvaginal suburethral sling removal from 2005 to 2015. We excluded patients with neurogenic bladder, nonsynthetic or multiple slings, prior mesh for prolapse, concomitant surgery during sling excision, urethral erosion or fistula, postoperative retention or less than 6‐month followup. Demographics, sling type, indications for removal, time to removal and patient reported outcomes were recorded. Outcomes were stratified by incontinence type, including stress predominant, urge predominant and mixed urinary incontinence. Subsequent management was evaluated, including observation, minimally invasive outpatient interventions (bulking agents, neuromodulation or onabotulinumtoxinA) or more invasive surgery (autologous fascial sling or bladder suspension). No patients elected to receive a subsequent synthetic sling. Success was defined by responses to UDI‐6 (Urogenital Distress Inventory) questions 2 and 3, self‐reported satisfaction with continence at the last visit and no further intervention. Results: Of the 99 patients who met inclusion criteria 27 denied any subjective leakage after suburethral sling removal alone while 72 experienced some degree of incontinence after removal. Stress predominant urinary incontinence occurred in 26 patients, which was persistent in 7 and de novo in 19, urge predominant incontinence was noted in 14, which was persistent in 6 and de novo in 8, and mixed urinary incontinence occurred in 32, which was persistent in 13 and de novo in 19. Mean followup was 23 months (range 6 to 114). The success rate following a single minimally invasive intervention after suburethral sling removal was 81%, 86% and 75% in patients with stress predominant, urge predominant and mixed urinary incontinence, respectively. Conclusions: Patients who undergo suburethral sling removal may show urinary control, or de novo or persistent incontinence with a higher predilection for stress predominant or mixed urinary incontinence. However, after a single minimally invasive intervention following suburethral sling removal the success rate reached 75% to 86%.

Urodynamics for incontinence after midurethral sling removal

We reviewed the role of urodynamics (UDS) in the management of women with incontinence following mid‐urethral sling removal (MUSR).

Prolapse Recurrence after Transvaginal Mesh Removal

PURPOSE We determined the rate of pelvic organ prolapse recurrence after transvaginal mesh removal. MATERIALS AND METHODS Following institutional review board approval a longitudinally collected database of women undergoing transvaginal mesh removal for complications after transvaginal mesh placement with at least 1 year minimum followup was queried for pelvic organ prolapse recurrence. Recurrent prolapse was defined as greater than stage 1 on examination or the need for reoperation at the site of transvaginal mesh removal. Outcome measures were based on POP-Q (Pelvic Organ Prolapse Quantification System) at the last visit. Patients were grouped into 3 groups, including group 1--recurrent prolapse in the same compartment as transvaginal mesh removal, 2--persistent prolapse and 3--prolapse in a compartment different than transvaginal mesh removal. RESULTS Of 73 women 52 met study inclusion criteria from 2007 to 2013, including 73% who presented with multiple indications for transvaginal mesh removal. The mean interval between insertion and removal was 45 months (range 10 to 165). Overall mean followup after transvaginal mesh removal was 30 months (range 12 to 84). In group 1 (recurrent prolapse) the rate was 15% (6 of 40 patients). Four women underwent surgery for recurrent prolapse at a mean 7 of months (range 5 to 10). Two patients elected observation. The rate of persistent prolapse (group 2) was 23% (12 of 52 patients). Three women underwent prolapse reoperation at a mean of 10 months (range 8 to 12). In group 3 (de novo/different compartment prolapse) the rate was 6% (3 of 52 patients). One woman underwent surgical repair at 52 months. CONCLUSIONS At a mean 2.5-year followup 62% of patients (32 of 52) did not have recurrent or persistent prolapse after transvaginal mesh removal and 85% (44 of 52) did not undergo any further procedure for prolapse. Specifically for pelvic organ prolapse in the same compartment as transvaginal mesh removal 12% of patients had recurrence, of whom 8% underwent prolapse repair.

Challenges of Multidimensional Outcome Reporting after Suburethral Mid Urethral Sling Removal

Purpose: We sought to determine the types and frequency of presenting symptoms in women undergoing suburethral mid urethral sling removal to improve outcome reporting after removal. Materials and Methods: Following institutional review board approval women who underwent suburethral mid urethral sling removal of 1 mid urethral sling were evaluated for their presenting symptoms and correlation with the UDI‐6 (Urogenital Distress Inventory‐Short Form) questionnaire. Demographic data were recorded. Patient reported presenting symptoms were categorized into 5 domains, including storage symptoms, voiding symptoms, pain, recurrent urinary tract infections or urinary incontinence. The UDI‐6 was reviewed preoperatively and 6 to 12 months postoperatively. We also calculated an ideal outcome, defined as resolution of incontinence, pain, resumption of sexual activity and no need for further anti‐incontinence procedures. Results: A total of 230 women from 2006 to 2017 met study inclusion criteria, including 116 who completed the UDI‐6 postoperatively. Of the women 80% had 3 or more presenting symptoms with pain as the most common symptom. The most common combination of symptoms was all 5 domains, which was noted in 46 of the 230 women (20%). An increasing number of symptoms correlated with the total preoperative UDI‐6 score. Symptom domains were associated with the corresponding UDI‐6 subdomain questions. Domains not covered by the UDI‐6, ie recurrent urinary tract infections and dyspareunia, accounted for 27% of reported symptoms. Due to limited data on sexual activity an ideal outcome was reached in 10% of patients but this rate was 40% after sexual activity information was excluded. Conclusions: In this series the presenting symptoms were manifold in women undergoing suburethral mid urethral sling removal. The UDI‐6 questionnaire correlated with many of these complaints. It may be used in outcome analysis in conjunction with self‐reported symptoms.

Impact of Allergy and Resistance on Antibiotic Selection for Recurrent Urinary Tract Infections in Older Women

OBJECTIVES To review the impact of antibiotic allergy and resistance in older women with recurrent urinary tract infections (RUTIs) as determinants for a suitable oral antibiotic treatment choice. METHODS A prospectively maintained database of women 65 years old and older with documented RUTIs (≥3 UTI/y) and trigonitis on cystoscopy was reviewed. Demographic data, known drug allergies, renal function, antibiotic susceptibility of most recent urine culture, allergy, or resistance to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones, and nitrofurantoin were obtained. RESULTS From 2006 to 2014, 86 women with RUTIs met study criteria. Mean age was 77.9 ± 7.8, with 94% being Caucasian. An estimated glomerular filtration rate >30 mL/min was noted in 94%. The percentage of women allergic, resistant, or both allergic and resistant to TMP-SMX was 33%, 29%, and 15%, to fluoroquinolones was 14%, 34%, and 8.1%, or nitrofurantoin was 16%, 14%, and 5%, respectively. Twenty-eight percent (24 of 86) of women who were allergic and/or resistant to TMP-SMX and fluoroquinolones were sensitive to nitrofurantoin. Twenty percent (17 of 86) were allergic and/or resistant to all 3 antibiotics. Women who were allergic or resistant to TMP-SMX had a significantly higher number of other antibiotic resistances compared with women sensitive to TMP-SMX (4.9 ± 3.6 vs 2.1 ± 2.3; P < .0001). Similarly, women with fluoroquinolone allergy or resistance had significantly more antibiotic resistances than those who were fluoroquinolone sensitive (5.8 ± 3.5 vs 2.3 ± 2.5; P < .0001). CONCLUSION Because of allergy and/or antibiotic resistance, several first-line antibiotics are not available for many older women with RUTIs. In nearly a third of women, nitrofurantoin was the only viable alternative.

PD26-09 STAGED APPROACH TO SLING REMOVAL IN WOMEN PRESENTING WITH PAIN ONLY

INTRODUCTION AND OBJECTIVES: Antimuscarinic are the current pharmacological mainstay for overactive bladder (OAB). However, adverse events resulting from antimuscarinics are inevitable in some patients. Discontinuation rates of 70% to 90% within the first year of therapy have been reported for various OAB medications, because the therapy did not produce the treatment bene?t expected. Mirabegron, which acts as a subtype of relaxation of detrusor, appeared on the Japanese market in 2011, and it provides a new treatment option for OAB. Currently, there are few published studies on the long-term persistence with drug therapy among OAB patients. The purposes of this study were to evaluate OAB pharmacotherapy adherence. METHODS: Patients 18 years of age or older who received an OAB diagnosis and OAB medication prescription for one ß3-adrenoceptor and six antimuscarinics were identified from April 2013 to August 2016. The study cohort consisted of 1,917 OAB patients in Aichi Medical University Hospital. Medication status such as persistence, switching, adherence and the reasons for discontinuation were examined. Persistence was measured by the length of continuous medication with OAB drugs. Time to discontinuation was defined as the number of days between the first dispense date and the expected end date of the last refill. The cumulative incidence of medication persistence was estimated using Kaplan-Meier method. Patients who remained on treatment until the end of the follow-up were regarded as censored data, and the length of follow-up period was assigned as the time of persistence. The proportion of persistence was compared according to each drug using the log-rank test. RESULTS: The mean patient age and time of persistence were 72.0 years and 323.9 days, and the following drugs were prescribed to OAB patients for 245 of imidafenacin, 24 of oxybutynin, 747 of solifenacin, 17 of tolterodine, 67 of fesoterodine, 100 of propiverine hydrochloride, and 723 of mirabegron. The 1-year persistence rate of each drug were 31.6%, 17.4%, 35.9%, 12.5%, 21.9%, 36.5% and 41.7%, respectively. The median of time to discontinuation were 184 days, 112 days, 196 days, 182 days, 77 days, 189 days and 231 days, respectively. Patients taking mirabegron demonstrated statistically significantly greater adherence than those taking antimuscarinics in both sexes. CONCLUSIONS: Mirabegron was associated with higher levels of persistence and adherence than antimuscarinics in our large and long term cohort.

S&T-41 IS THERE A DIFFERENCE IN OUTCOME BETWEEN EARLY VERSUS DELAYED REMOVAL OF SUBURETHRAL MID-URETHRAL SLING?

Study design, materials and methods: A prospectively maintained, institutional review board approved, database of consecutive non-neurogenic women who underwent SSR for MUS complications and were followed for 6 months minimum was reviewed. Exclusion criteria included women with existing vaginal mesh in place, those who underwent concomitant vaginal mesh removal or concomitant surgery, or had 2 MUS removed. All MUS excisions were performed vaginally under general anaesthesia with the aim of removing as much MUS as possible. [1] Indications for SSR and outcomes at the last visit were classified based on patient self-reporting.

MP75-11 LONG-TERM OUTCOME OF UTERINE SPARING PROCEDURE AS PART OF ANTERIOR VAGINAL WALL SUSPENSION.

and QoL consistently improved post-operatively, and remained stable over time (Table 1). VCUG findings also improved for urethral support and cystocele reduction. Additional therapy with sling (4) or injectable agents (8) was required in 12 (6%) women at a median of 3.8 (1.2-10.3) years. CONCLUSIONS: The AVWS procedure can durably correct SUI by restoration of anatomical support to the bladder neck and bladder base. Reference: 1. Wilson TS, Zimmern PE: Anterior Vaginal Wall Suspension, Female Urology, Urogynecology, and Voiding Dysfunction, Vasavada, Appell, Sand, and Raz, Section I, Chapter 17, 283-290, Marcel Dekker, 2005