Pharmacotherapy in Stress Urinary Incontinence; A Literature Review.

PURPOSE OF REVIEW: Stress urinary incontinence (SUI) is a commonly observed condition in females, as well as in males who have undergone prostatectomy. Despite the significant progress made in surgical techniques, pharmacotherapy has not yielded substantial outcomes within the clinical domain. This review aims to present a comprehensive overview of the existing pharmacotherapy options for stress urinary incontinence (SUI) and the emerging therapeutic targets in this field. RECENT FINDINGS: One meta-analysis demonstrated that α-adrenergic medications are more efficacious in improving rather than curing SUI symptoms. One trial showed reduced pad weight gain with PSD-503, a locally administered α-adrenergic receptor agonist. New data show that duloxetine's risk outweighs its benefits. One small-scale trial was found to support the use of locally administered estriol in improving subjective outcomes. Emerging targets include serotonin 5HT2C agonists, selective inhibitors of norepinephrine uptake, and myostatin inhibitors. Only one of the evaluated drugs, duloxetine, has been approved by some countries. Currently, trials are evaluating novel targets. Systemic adverse effects such as gastrointestinal upset with duloxetine and orthostatic hypotension with α-adrenoceptor agonists have hampered the efficacy of drugs used to treat SUI in women and men.

Autologous rectus fascia sling for treatment of stress urinary incontinence in women: A review of the literature.

AIMS: Stress urinary incontinence (SUI) is common in the adult females. Surgical treatment options include synthetic mid-urethral sling (MUS), autologous sling, bulking agents, and Burch colposuspension. The autologous pubovaginal sling (PVS) has re-emerged in response to complications of synthetic MUSs and FDA communications regarding the use of vaginal mesh. This resulted in patients' fear related to vaginal mesh and drop in number of patients seeking surgical treatment of SUI. PVS has re-emerged as an option for treatment of primary SUI. The aim of this review is to familiarize, disseminate information, and share tips for the practicing female pelvic surgeons related to the practice of the autologous fascia sling. METHODS: We reviewed the literature related to the autologous sling. We used the following data bases and search engines: GoPubMed (Transinsight), Cochrane reviews (Wiley Interscience), google scholar (google), and Scopus (Elsevier). Because it is the most commonly investigated and utilized, we focused on the autologous rectus fascia sling. We also focused on the retropubic sling approach because the literature on transobturator rectus fascia sling is sparse. RESULTS: Out of 307 articles related to the subject found, 22 articles were included and the rest were excluded. CONCLUSION: ARFS is a valid primary method of treatment for female SUI. Also, it is used in particular indications such as patients with intrinsic sphincter deficiency (ISD), prior pelvic irradiation, failed and/or complicated synthetic MUS, and violated urethral lumen.

Patient-Reported Outcome Measures (PROMs) in Pelvic Floor Disorders.

PURPOSE OF REVIEW: Patient-reported outcome measures (PROMs) are tools that are widely used by clinicians and researchers across different medical specialties. In this review, we examine the use of PROMs in the evaluation of female pelvic floor disorders (PFD). RECENT FINDINGS: PROM development in the assessment of urinary incontinence is more advanced than other pelvic disorders. Work is ongoing in the scientific community to improve currently available measures and create new robust tools where needed. Hundreds of PROMs are available for use in the evaluation of PFD, some more rigorously validated than others. They are used to screen for diseases, evaluate their impact on quality of life, determine the results of treatment, and measure patient's satisfaction with treatment. Careful consideration is required to choose the appropriate PROMs to care for a patient or include in a research study. The topic was reviewed in the Textbook of Female Urology and Urogynecology published in 2017. We reviewed recent literature (2015-2018) on the topic and summarized our findings.

Novel management approach to connecting tube erosion of artificial urinary sphincter.

Artificial urinary sphincter (AUS) erosion often involve the urethral cuff and is managed by complete or partial device removal. Abdominal wall erosion of AUS tubing has not been previously reported and its management is unknown. We report tube erosion (TE) of AUS successfully managed without device explant. An 81-year-old male with AUS for post-prostatectomy incontinence presented with TE at the site of inguinal incision without signs or symptoms of infection. The exposed tube was reduced and wound was closed after copious antibiotic solution irrigation. No complications were noted at 2 month follow up. AUS-TE can be successfully managed conservatively with antiseptic wound site irrigation and reinsertion in absence of infection.

Vaginal repair of ureterovaginal fistula may be suitable for selected cases.

Ureterovaginal fistula (UVF) is an uncommon but devastating complication of gynecologic surgery. Management includes ureteral stenting for 6-8 weeks. For stent failure, ureteroneocystostomy (UNC) through an open, laparoscopic, or robotic abdominal approach is the classic alternative. Originally pioneered for repair of vesicovaginal fistulas (VVF), the use of the vaginal approach in UVF is scarcely reported in the literature. We report the successful repair of UVF performed exclusively through the vaginal approach in two women after robotic hysterectomy. In select clinical scenarios, this approach may be applied, as it provides a minimally invasive option for managing UVF after failure of ureteral stenting.

The outcome of transobturator anterior vaginal wall prolapse repair using porcine dermis graft: intermediate term follow-up.

INTRODUCTION AND HYPOTHESIS: We evaluated the anatomical success and complications of Perigee® with porcine dermis Graft in the repair of anterior vaginal wall prolapse (AVWP) MATERIALS AND METHODS: After Institutional Review Board (IRB) approval, the charts of all patients who underwent AVWP repair using the Perigee/InteXen® kit from July 2005 to July 2009 were reviewed. Patients who had less than 6-month follow-up were excluded. Preoperative data including patient age, previous AVWP repairs, hysterectomy status, preoperative dyspareunia and pertinent physical findings were collected and recorded. Postoperative success was defined as anatomical stage 0 or I using the Pelvic Organ Prolapse Quantification (POP-Q) scoring system. Graft related complications were also recorded. RESULTS: Out of 89 patients, 69 completed at least 6-month follow-up. Median follow-up was 13 (6-48) months. Seventeen patients (25%) had previous AVWP repair and 32 (46%) had previous hysterectomy. Preoperatively, AVWP stage II was found in 9 (13%), stage III in 27 (39%) and stage IV in 33 (48%) patients. Anatomic success was found in 48 (69%) patients, with 23 (33%) having stage 0 and 25 (36%) stage I AVWP. Intraoperative complications included incidental cystotomy in one patient and bladder perforation in one. Postoperative complications included vaginal exposure and dyspareunia in one case, wound dehiscence in one and tenderness over the graft arm with dyspareunia in one. CONCLUSIONS: The use of porcine dermis in AVWP repair is safe with minimal graft related complications; however, anatomical success is lower than that reported with the use of synthetic grafts.

Microbial colonization of sacral nerve stimulators pseudo-capsule: A single institution experience.

PURPOSE: To evaluate the incidence and type of microbial colonization of the pseudo-capsule (PC) that forms around sacral nerve stimulators (SNS) and consequently the significance of surgical excision of this PC at time of SNS revision or removal. MATERIALS AND METHODS: A cohort of 31 patients who underwent SNS revision or removal from January 2018 to June 2021 were retrospectively reviewed. The baseline demographics, rate and type of PC microbial colonization and development of SNS insertion site infection were reported. RESULTS: A cohort of 31 patients who underwent "InterStim device (Medtronic)" revision or removal were included. The majority were females (93.5%). The most common indication for SNS insertion was refractory overactive bladder (67.7%). Nine patients (29.0%) underwent SNS revision due to malfunctional device, and 9 patients had SNS removal for the need of MRI procedures. Four patients (12.9%) had positive tissue culture growing Coryneform bacillus (50.0%), Cutibacterium acnes (25.0%) and Pseudomonas aeruginosa (25.0%). CONCLUSIONS: PC colonization was uncommon at the time of SNS explant. However, more research is needed to better understand the role of PC-positive culture in increasing the risk of SNS device infections if strict adherence to sterile techniques is adopted.

Efficacy and safety of TURP, HoLEP, and PVP in the management of OAB symptoms complicating BPH in patients with moderately enlarged prostates: A comparative study.

INTRODUCTION: We aimed to compare the effectiveness and safety of transurethral resection of the prostate (TURP), holmium laser enucleation of the prostate (HoLEP), and photoselective vaporization of the prostate (PVP) in management of storage and overactive bladder (OAB) symptoms complicating benign prostatic hyperplasia (BPH) in patients with moderately enlarged prostates. METHODS: The charts of patients with moderately enlarged prostates and BPH complicated by storage and OAB symptoms who were treated by TURP, HoLEP, and PVP at University of Cincinnati hospitals between March 2012 and December 2020 were retrospectively reviewed and analyzed for changes in storage and OAB symptomatology, International Prostate Symptom Score (IPSS), peak flow rates (Qmax), presence of detrusor overactivity (DO), and postvoid residual (PVR) from baseline to up to six months postoperatively. RESULTS: A total of 204 patients with moderately enlarged prostates and BPH complicated by storage and OAB symptoms were divided into three groups: group 1 (patients who underwent TURP, 89 patients), group 2 (those who underwent HoLEP, 64 patients), and group 3 (those who underwent PVP, 51 patients). TURP, HoLEP, and PVP were associated with significant improvement in urodynamics study (UDS) parameters, patient storage and OAB symptomatology, and IPSS from preoperatively to both three and six months postoperatively in BPH patients with moderately enlarged prostates, with relatively low procedure complication rate and postoperative need for either anticholinergic or procedure. CONCLUSIONS: TURP, HoLEP, and PVP are effective and reliable surgical procedures that can be relied upon for BPH patients with moderately enlarged prostates and storage or OAB symptoms, with comparable efficacy and relatively low procedure complication rate and postoperative need for anticholinergic or additional procedure.

Extensive gluteal hematoma following InterStim implant: a case report.

Major bleeding complications following sacral nerve stimulation (SNS, InterStim) are exceptionally rare and have not been reported in the literature. We report a case of extensive gluteal hematoma following SNS procedure in a woman with a known history of thrombophilia.

Outcomes of continent and incontinent external urinary diversion in management of patients with refractory non-malignant lower urinary tract dysfunction.

OBJECTIVE: To evaluate the early and late outcomes of continent and incontinent external urinary diversion in management of patients with refractory non-malignant lower urinary tract dysfunction (LUTD). MATERIALS AND METHODS: The charts of patients with refractory non-malignant LUTD who underwent continent or incontinent external urinary diversion at University of Cincinnati hospitals in the period between March 2012 and December 2019 were retrospectively reviewed. The demographic and baseline characteristics, surgery indications, operative data, early and late outcomes were collected, analyzed, and compared. RESULTS: A total of 78 patients including 55 patients with neurogenic bladder (NGB) and 23 patients with non-neurogenic bladder (non-NGB) refractory non-malignant LUTD were included. Fifty-three patients underwent incontinent urinary diversions (IUD), while 25 patients underwent continent urinary diversions (CUD). During the first 4 postoperative weeks, 53.85% (n=42) of patients developed complications, and the incidence was nonsignificantly higher in patients with NGB than those with non- NGB (56.36% vs 47.83%, p-value=0.490). Fever was exclusively encountered in patients with NGB earlier, while stomal retraction occurred only in patients with non-NGB later. More non- NGB patients had early wound infection. There was an overall improvement of urological symptoms in 52 patients (66.67%), and the rate was non-significantly higher in non-NGB patients than NGB patients (78.26% vs 61.82%, p-value=0.160). Late complications were reported in 47 patients and were more encountered in those with non-NGB than those with NGB (65.22% vs 58.18%). Stomal leakage and stenosis occurred more with CUD than with IUD (52% vs 0% and 28% vs 3.77%, respectively). CONCLUSIONS: External urinary diversion can achieve a reasonable level of urological symptoms control in patients with refractory non-malignant LUTD, but with associated adverse outcomes. Although non-significantly, these complications tend to be higher in patients with IUD and/or NGB during the early postoperative period and higher with CUD and/or non-NGB on the long-term.

Is Holmium Laser Enucleation of Prostate equally effective in management of benign prostatic hyperplasia patients with either voiding or storage lower urinary tract symptoms? A comparative study.

OBJECTIVE: To evaluate and compare the effectiveness and safety of holmium laser enucleation of prostate (HoLEP) in relieving either voiding or storage lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH) patients. MATERIALS AND METHODS: The charts of patients with BPH who underwent HoLEP for either predominant voiding or predominant storage LUTS at University of Cincinnati hospitals in the period between February 2015 and December 2020 were retrospectively reviewed and analyzed for changes in voiding symptomatology, storage symptomatology, hematuria, International Prostate Symptom Score (IPSS), peak flow rates (Qmax), presence of detrusor overactivity (DO), and post-voiding residual urine (PVR) from baseline to up to 6 months postoperatively. RESULTS: A total of 132 patients were included in the analysis. Patients were divided into two groups: Group 1 included BPH patients with predominant voiding LUTS (68 Patients) while group 2 involved those with predominant storage LUTS (64 Patients). HoLEP was equally effective in management of both groups with significant improvement in urodynamics study (UDS) parameters, patient voiding and storage symptomatology, and IPSS from preoperatively to up to 6 months postoperatively with relatively low procedure complication rate and postoperative need for medication or procedure. CONCLUSIONS: HoLEP is a safe, effective, and reliable minimally invasive surgical modality that can be relied on for BPH patients with either predominant voiding or predominant storage symptoms with relatively low procedure complicat.

Transvaginal Mesh Compared With Native Tissue Repair for Pelvic Organ Prolapse.

OBJECTIVE: To compare the safety and effectiveness of transvaginal mesh repair and native tissue repair, in response to a U.S. Food and Drug Administration (FDA) 522 study order to assess co-primary endpoints of superiority and noninferiority. METHODS: This was a prospective, nonrandomized, parallel cohort, multi-center trial comparing transvaginal mesh with native tissue repair for the treatment of pelvic organ prolapse. The primary endpoints were composite treatment success at 36 months comprised of anatomical success (defined as pelvic organ prolapse quantification [POP-Q] point Ba≤0 and/or C≤0), subjective success (vaginal bulging per the PFDI-20 [Pelvic Floor Distress Inventory]), and retreatment measures, as well as rates of serious device-related or serious procedure-related adverse events. Secondary endpoints included a composite outcome similar to the primary composite outcome but with anatomical success defined as POP-Q point Ba<0 and/or C<0, quality-of-life measures, mesh exposure and mesh- and procedure-related complications. Propensity score stratification was applied. RESULTS: Primary endpoint composite success at 36 months was 89.3% (201/225) for transvaginal mesh and 80.2% (389/485) for native tissue repair, demonstrating noninferiority at the preset margin of 12% (propensity score-adjusted treatment difference 6.5%, 90% CI -0.2% to 13.2%). Using the primary composite endpoint, transvaginal mesh was not superior to native tissue repair (P=.056). Using the secondary composite endpoint, superiority of transvaginal mesh over native tissue repair was noted (P=.009), with a propensity score-adjusted difference of 10.6% (90% CI 3.3-17.9%) in favor of transvaginal mesh. Subjective success for both the primary and secondary endpoint was 92.4% for transvaginal mesh, 92.8% for native tissue repair, a propensity score-adjusted difference of -4.3% (CI -12.3% to 3.8%). For the primary safety endpoint, 3.1% (7/225) of patients in the transvaginal mesh (TVM) group and 2.7% (13/485) of patients in the native tissue repair (NTR) group developed serious adverse events, demonstrating that transvaginal mesh was noninferior to native tissue repair (-0.4%, 90% CI -2.7% to 1.9%). Overall device-related and/or procedure-related adverse event rates were 35.1% (79/225) in the TVM group and 46.4% (225/485) in the NTR group (-15.7%, 95% CI -24.0% to -7.5%). CONCLUSION: Transvaginal mesh repair for the treatment of anterior and/or apical vaginal prolapse was not superior to native tissue repair at 36 months. Subjective success, an important consideration from the patient-experience perspective, was high and not statistically different between groups. Transvaginal mesh repair was as safe as native tissue repair with respect to serious device-related and/or serious procedure-related adverse events. FUNDING SOURCE: This study was sponsored by Boston Scientific and developed in collaboration with FDA personnel from the Office of Surveillance and Biometrics, Division of Epidemiology. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01917968.

Biologic grafts for cystocele repair: does concomitant midline fascial plication improve surgical outcomes?

INTRODUCTION AND HYPOTHESIS: This study aims to compare the efficacy of porcine graft-augmented anterior prolapse repair with and without underlying pubocervical fascia plication. METHODS: Women with symptomatic anterior prolapse who underwent transvaginal repair, using biologic graft via transobturator approach, were retrospectively studied. An initial cohort had the graft placed without fascial plication. A second cohort had graft placement as an overlay to fascial plication. RESULTS: Between March 2005 and September 2008, 65 subjects underwent anterior repair with biologic graft; 35 without fascial plication and 30 as an overlay to plication. At 6 months follow-up, anatomic recurrence (Ba>/= -1) was significantly higher in the non-plicated group (18/35, 51%) compared with the plicated group (2/30, 7%) p < 0.01. Five (5/35, 14%) in the non-plicated group compared with none (0/30) in the plicated group underwent further treatment (p = 0.06). CONCLUSIONS: When using a non-crosslinked biologic graft for repair of anterior vaginal prolapse, we recommend the addition of concomitant midline fascial plication to enhance anatomic outcome.

Differential profile analysis of urinary cytokines in patients with overactive bladder.

INTRODUCTION AND HYPOTHESIS: We hypothesize that overactive bladder (OAB) can produce inflammatory cytokines due to afferent neural plasticity or urothelial dysfunction. This study aimed to detect abnormal cytokine levels in urine of patients with OAB compared to urinary tract infections (UTI) and controls. METHODS: This was a prospective, single blind study including 20 premenopausal women (control), 20 with OAB and 16 with UTI. Urine samples were collected, centrifuged, and stored (-80°C). Urinary total proteins were quantified and detected by antibody-based array chip for release of 120 human cytokines in the two groups relative to the controls. RESULTS: Majority of cytokines showed the same expression in the OAB compared with the controls. Cytokines exclusively expressed in OAB were: monocyte chemoattractant protein (MCP) 1, TARC, PARC, and Fas/TNFRSF6. MCP-2, MCP-3, tumor necrosis factor-ß, GCSF and eotaxin-3 showed a shared expression in UTI and OAB. Conversely, few of the cytokines were downregulated in OAB (IL-5, IL-6, IL-7, and GM-CSF). CONCLUSIONS: Taken together, the results suggest that a subset of inflammatory cytokines and chemokines provides a framework for development of highly optimized urinary biomarker assay for differential diagnosis and treatment of OAB.

Treatment of female stress urinary incontinence: what women find acceptable and the impact of clinical and urodynamic evaluation on their final choice.

OBJECTIVES: The aim of this study was determine what women find acceptable regarding treatment modality for Stress urinary incontinence (SUI) and to assess the impact of clinical and urodynamic evaluation on their final decision. MATERIAL AND METHODS: This prospective, institutional review board-approved study included 100 consecutive women with primary SUI. All women were given a questionnaire that included the Urinary Distress Inventory (UDI-6) and the American Urologic Association Quality of Life questionnaire (AUA-QoL6). The patients were also asked to choose one of the four available treatment options, which included major surgeries, minor surgeries, office procedures and medication. Factors affecting the initial choice of treatment were studied. A Q-tip test and multichannel urodynamics were then carried out and the patients were recounseled by the urologist. The patients' final decision was compared with their initial choice and statistical analysis was performed. RESULTS: Initially, 22% patients chose major surgery, 39% minor surgery, 27% an office procedure and 12% medication. This was affected by age, symptom severity and quality of life bother. After clinical and urodynamic evaluation, 34% shifted to a different treatment modality; this correlated significantly with young age, severe symptoms, limited urethral mobility and low Valsalva leak point pressure. CONCLUSIONS: Patients' initial choice for treatment of SUI was affected by age, symptom severity and quality of life; however, the final decision was more influenced by the clinical and urodynamic evaluation. It is important to counsel the patients before definitive treatment, to achieve a better outcome.

Early Postoperative Complications and Factors Associated with Early vs Late Discharge of Patients Undergoing Colporrhaphy for Pelvic Organ Prolapse: A National Report.

INTRODUCTION: Pelvic organ prolapse is a highly prevalent condition that is commonly managed with surgical intervention. Our purpose was to determine associated factors and postoperative morbidity rates of early (≤1 day) vs late (>1 day) hospital discharge after outpatient colporrhaphy. METHODS: From the National Surgical Quality Improvement Program® database, 11,652 female patients who received colporrhaphy between 2005 and 2016 were identified; 3,728 were stratified into the early discharge group and 7,924 into the late discharge group. Patient characteristics, surgical data and 30-day postoperative complications were recorded, and variables were compared between groups. RESULTS: In comparison to the late discharge group, the early discharge group had a shorter mean operating time (p <0.001) and overall was less likely to suffer from 30-day morbidity (OR 0.67 [95% CI 0.55-0.82]), reoperation (OR 0.59 [95% CI 0.39-0.90]) or readmission (OR 0.40 [95% CI 0.26-0.90]). Factors independently associated with a lower likelihood of early discharge included age ≥55 years, higher body mass index, White race, current smoker, American Society of Anesthesiologists® classification IV/V and longer operating time. Increased likelihood of early discharge was associated with receiving colporrhaphy after 2012 and posterior colporrhaphy. CONCLUSIONS: Patients discharged from the hospital early had lower rates of postoperative morbidity than those discharged later. Early discharge was associated with procedures performed after 2012 and with isolated posterior colporrhaphy. Longer hospital stays were associated with longer operating times and older age, White race, obesity, comorbidities and history of smoking.

Acid ceramidase upregulation in prostate cancer cells confers resistance to radiation: AC inhibition, a potential radiosensitizer.

Radiation resistance in a subset of prostate tumors remains a challenge to prostate cancer radiotherapy. The current study on the effects of radiation on prostate cancer cells reveals that radiation programs an unpredicted resistance mechanism by upregulating acid ceramidase (AC). Irradiated cells demonstrated limited changes of ceramide levels while elevating levels of sphingosine and sphingosine-1-phosphate. By genetically downregulating AC with small interfering RNA (siRNA), we observed radiosensitization of cells using clonogenic and cytotoxicity assays. Conversely, AC overexpression further decreased sensitivity to radiation. We also observed that radiation-induced AC upregulation was sufficient to create cross-resistance to chemotherapy as demonstrated by decreased sensitivity to Taxol and C(6) ceramide compared to controls. Lower levels of caspase 3/7 activity were detected in cells pretreated with radiation, also indicating increased resistance. Finally, utilization of the small molecule AC inhibitor, LCL385, sensitized PPC-1 cells to radiation and significantly decreased tumor xenograft growth. These data suggest a new mechanism of cancer cell resistance to radiation, through upregulation of AC that is, in part, mediated by application of the therapy itself. An improved understanding of radiotherapy and the application of combination therapy achieved in this study offer new opportunities for the modulation of radiation effects in the treatment of cancer.