Anterior Vaginal Wall Prolapse Repair and the Rise and Fall of Transvaginal Mesh. Did We Come Full Circle? A Historical Perspective.

OBJECTIVE: To present a brief historical review of treatment options for pelvic organ prolapse with a focus on anterior vaginal wall defects and highlight changing practice patterns in the era of synthetic mesh controversy. METHODS: A MEDLINE and PubMed search was performed using the keywords pelvic organ prolapse, anterior colporrhaphy, and cystocele followed by a manual search of bibliographies. RESULTS: Ancient treatments included Hippocratic succession, local astringent, and use of pomegranates as crude pessaries. More sophisticated surgical techniques evolved in the 19th century with further refinement in the early 20th century. Numerous native tissue apposition techniques were popularized by Kelly, Kennedy, Burch, and Raz. Due to poor durability, surgeons sought alternate approaches including biologic and synthetic grafts. Synthetic transvaginal mesh (TVM) initially included use of Tantalum and Marlex to repair anterior wall defects. Both were eventually abandoned due to complications. TVM was re-designed, re-marketed, and re-introduced. Type 1 polypropylene monofilament TVM use became ubiquitous in female pelvic surgery peaking between 2004 and 2008. Initial promising outcomes were soon eclipsed by a surge of adverse events leading to multiple FDA warnings, reclassification to Class III, high-risk medical device, and ultimately a complete recall in 2019. CONCLUSION: The bidirectional pendulum swing on use of synthetic TVM has been occurring since its introduction 50 years ago. In the current era of mesh controversy, more practitioners are now revisiting previously described native tissue and biologic graft techniques. It appears that history has repeated itself.

Long-Term Treatment with OnabotulinumtoxinA Results in Consistent, Durable Improvements in Health Related Quality of Life in Patients with Overactive Bladder.

PURPOSE: We present the long-term effects of repeat onabotulinumtoxinA 100 U treatment on health related quality of life in patients with overactive bladder and urinary incontinence who had an inadequate response to and/or were intolerant of an anticholinergic. MATERIALS AND METHODS: Patients who completed either of 2, 24-week phase III trials could enter a 3-year extension study and request multiple onabotulinumtoxinA 100 U treatments as needed. Results of the I-QOL (Incontinence-Quality of Life) and KHQ (King's Health Questionnaire) are reported for up to 6 treatments. Consistency of the response to repeat onabotulinumtoxinA treatments was evaluated by classifying patients by the I-QOL response to the first treatment and analyzing responses to treatments 2 to 6. RESULTS: After onabotulinumtoxinA treatments 1 to 6, improvements in I-QOL scores were consistently 2 to 3 times the minimally important difference, and improvements in KHQ role limitations and social limitations domain scores were 5 to 6 and 3 to 4 times the minimally important difference, respectively. Most patients achieved or exceeded the minimally important difference for I-QOL and KHQ domain scores. Furthermore, 72.9% of patients who achieved or exceeded the minimally important difference for I-QOL after treatment 1 did so for all subsequent treatments. Of patients with a poor response after treatment 1, 38.3% achieved improvements greater than the minimally important difference for all subsequent treatments. CONCLUSIONS: In patients with overactive bladder and incontinence consistent and clinically meaningful improvements in health related quality of life were observed with repeat onabotulinumtoxinA 100 U treatments. A positive response after treatment 1 tended to predict similar responses to subsequent treatments, whereas a lack of response to treatment 1 did not preclude positive response(s) to later treatments.

Mixed urinary incontinence: what first?

Mixed urinary incontinence (MUI) is the involuntary loss of urine associated with the sensation of urgency and also with exertion, effort, sneezing, or coughing. The underlying cause of MUI is poorly understood. Without clearly understanding the pathophysiological and anatomical changes associated with MUI, treatment is often misdirected. This review presents an analysis of the most recent studies and pathophysiological mechanisms thought to be associated with MUI-related voiding dysfunction. A suggested algorithm is provided for the workup of these women with a review of medical and surgical treatment options used to treat MUI.

A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the ß3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder.

OBJECTIVE: To assess the efficacy and tolerability of mirabegron 25 mg and 50 mg once-daily vs placebo in patients with overactive bladder (OAB). MATERIALS AND METHODS: Patients ≥18 years with OAB symptoms were recruited to a 2-week, single-blind, placebo run-in. Those with ≥8 micturitions per 24 hours and ≥3 urgency episodes were randomized 1:1:1 to once-daily mirabegron 25 mg or 50 mg, or placebo for 12 weeks. Primary endpoints were changes to final visit in mean number of incontinence episodes and micturitions per 24 hours. Key secondary endpoints were changes to final visit in mean volume voided or micturition, change to week 4 in mean number of incontinence episodes and micturitions per 24 hours, changes to final visit in mean level of urgency, number of urgency incontinence episodes, and urgency (grade 3 or 4) episodes per 24 hours. Patient-reported outcomes were assessed using the OAB-questionnaire, Patient Perception of Bladder Condition, and Treatment-Satisfaction-Visual Analog Scale. RESULTS: Both mirabegron groups demonstrated statistically significant improvements in coprimary endpoints vs placebo. Mirabegron 50 mg demonstrated significantly greater improvements vs placebo in the following: change to final visit in mean volume voided per micturition and change to week 4 in mean number of incontinence episodes per 24 hours. Statistically significant improvements vs placebo were demonstrated by mirabegron 50 mg in all patient-reported outcome scales with no increase in the incidence of treatment-emergent adverse events vs placebo. CONCLUSION: Mirabegron 25 mg and 50 mg were associated with significant improvements in efficacy measures of incontinence episodes and micturition frequency. Mirabegron was well tolerated vs placebo.

Role of botulinum toxin-A in refractory idiopathic overactive bladder patients without detrusor overactivity.

BACKGROUND: To evaluate the efficacy of intradetrusor botulinum toxin-A (BTX-A) in idiopathic overactive bladder patients (OAB) refractory to anti-muscarinic therapy, without detrusor overactivity (DOA) on urodynamics. METHODS: Patients with refractory idiopathic OAB without DOA on urodynamics were prospectively enrolled. Subjects completed a 3-day voiding diary (3-VD), urogenital distress inventory-6 questionnaire (UDI-6) and graded their quality of life on a 10-cm visual analog scale (VAS) prior to study enrollment and at week 12 postinjection. All patients underwent multichannel urodynamics at study enrollment and 12 weeks postinjection. Improvement was analyzed based on 3-VD, UDI-6 questionnaire, VAS scores, and urodynamic parameters at week 12 postinjection compared to study enrollment. RESULTS: The study included 32 patients. Mean ± SD age was 56 ± 16. There were 27 women and 5 men. Nineteen patients had OAB without incontinence (OAB-dry) and 13 patients had OAB with incontinence (OAB-wet). In OAB-dry patients, mean ± SD urinary frequency dropped from 24 ± 11 to 10 ± 4 by week 12. In OAB-wet patients, mean ± SD urge incontinence episodes dropped from 7.9 ± 5 to 0 ± 2.6 by week 12. Mean UDI-6 and VAS scores improved significantly in both groups by week 12 (P = 0.0001). On comparing urodynamic parameters, OAB-wet patients showed significant decrease in maximum detrusor pressure during the voiding phase at week 12 compared to baseline values (P = 0.02). CONCLUSIONS: Refractory idiopathic OAB patients without DOA on urodynamics may benefit from intradetrusor BTX-A.

Bladder dysfunction in patients with diabetes.

With diabetes mellitus (DM) reaching epidemic proportions, the identification of voiding dysfunction as a common and burdensome complication of this disease is critical. Research into diabetic voiding dysfunction significantly lags behind other complications of DM, such as retinopathy and nephropathy. Recent studies have revealed that DM predisposes patients to a wide range of lower urinary tract dysfunction, from the classic diabetic cystopathy of incomplete emptying to urgency incontinence. In this review, we discuss the current concepts of diabetic voiding dysfunction with a critical analysis of the available evidence.

Voiding dysfunction in the female patient: is the "syndrome" paradigm valid?

Voiding dysfunction in the female patient significantly affects the patient's quality of life. The condition is poorly understood, has varied etiology and clinical presentation, and lacks standard definitions with no consensus on diagnostic criteria. It consists of a constellation of symptoms involving both phases of the micturition cycle. Appropriate diagnosis and treatment of female lower urinary tract symptoms (LUTS) is of paramount importance. However, the differentiation of female LUTS into various syndromes is currently controversial. This article comprehensively reviews the commonly encountered female non-neurogenic LUTS (overactive bladder, interstitial cystitis, and painful bladder syndrome); discusses the contemporary management of these syndromes; and emphasizes a syndromic approach to the condition.

Repeat intradetrusor injections of onabotulinum toxin a for refractory idiopathic overactive bladder patients: a single-center experience.

OBJECTIVES: : The objective of the study was to evaluate the safety and efficacy of repeat intradetrusor onabotulinum toxin A injection in patients with idiopathic overactive bladder refractory to anticholinergic medications. Furthermore, 2 doses, 100 and 150 U, were compared. METHODS: : We prospectively enrolled 60 patients in our investigator-initiated, single-center randomized trial. Thirty patients were randomized to each dosage arm. Total study duration was 3 years. Patients were eligible to receive 6 onabotulinum toxin A injections. Subjects completed a 3-day voiding diary and Urogenital Distress Inventory 6 (UDI-6) questionnaire and graded their quality of life on a visual analog scale (VAS) before study enrollment and at week 6 after every injection. The outcome was based on the amount of improvement noted on the UDI-6 and VAS scores at 6 weeks post every injection as compared with study enrollment. RESULTS: : There were 9 men and 51 women. The mean UDI-6 and VAS scores improved significantly (P = 0.0001) at week 6 after initial onabotulinum toxin A injection, and no change was seen when comparing repeat injections; 20% and 10% of the patients randomized to 150 and 100 U required performing clean intermittent catheterization, respectively. The mean UDI-6 scores after repeat onabotulinum toxin A injections did not differ significantly between 100 and 150 U. CONCLUSIONS: : Repeat injections of onabotulinum toxin A are capable of significantly improving UDI-6 scores and quality of life in refractory patients with idiopathic overactive bladder. There was no evidence of decreased efficacy after repeat injections. Lower clean intermittent catheterization rates were noted in patients randomized to 100 U as compared with 150 U. Both doses, 100 and 150 U, were equally efficacious.

What is the predictive value of urodynamics to reproduce clinical findings of urinary frequency, urge urinary incontinence, and/or stress urinary incontinence?

INTRODUCTION AND HYPOTHESIS: The aim of this study was to determine the predictive value of urodynamics to reproduce clinical findings of urinary frequency (UF), urge urinary incontinence (UUI), and/or stress urinary incontinence (SUI). METHODS: We retrospectively reviewed the data of patients diagnosed with UF, UUI, and/or SUI and subsequently underwent urodynamics. Urodynamic findings were correlated with clinical findings to determine the predictive value of urodynamics. RESULTS: A total of 537 patients (366 females and 171 males) met study criteria. Two hundred seventy-eight patients had symptoms of UUI; 59% demonstrated detrusor overactivity on urodynamics. Three hundred eight patients had SUI on history and physical examination; 45% had urodynamic stress incontinence. A low maximum cystometric capacity (<200 ml) was not significantly associated with urinary frequency (p = 0.4). CONCLUSIONS: Urodynamics has a low predictive value to reproduce clinical findings of UF, UUI, and/or SUI. Many patients with evidence of UF, UUI, and/or SUI on history and/or physical examination do not demonstrate supporting urodynamic evidence.

Predictors of response to intradetrusor botulinum toxin-A injections in patients with idiopathic overactive bladder.

OBJECTIVES: To evaluate whether there are any demographic or urodynamic differences in patients with idiopathic overactive bladder (I-OAB) that respond and do not respond to intradetrusor injections of botulinum toxin-A (BTX-A). METHODS: This represents a secondary analysis of data collected from an investigator initiated randomized trial designed to evaluate clinical differences in outcomes for 100 versus 150 U BTX-A in patients with I-OAB. Preinjection demographic and urodynamic data were collected. Patients were evaluated 12 weeks after injection and were determined to be responders or nonresponders as defined by our criteria. Statistical comparisons were made between groups. RESULTS: In patients with overactive bladder without incontinence (OAB-Dry), there were no variables that could be used to predict response to BTX-A. On univariate analysis, younger patients with overactive bladder with incontinence (OAB-Wet) were more likely to respond to BTX-A than older patients. However, this relationship was no longer statistically significant on multivariate analysis. CONCLUSIONS: We were unable to identify any preinjection demographic or urodynamic parameters that could aid in predicting which patients will achieve clinical response to BTX-A. Future studies are necessary to further evaluate this question.

Medical management of stress urinary incontinence: is there a future?

Stress urinary incontinence (SUI) is a common problem among women worldwide. Multiple treatment modalities exist, ranging from physiotherapy to surgery. Numerous reports demonstrate mixed results for efficacy and safety of several oral agents used to treat SUI. Although there are data suggesting reasonable efficacy for several medications, surgery still remains the mainstay of treatment for most women. This article reviews the available oral agents that have been studied and assesses the data supporting their use while highlighting the limitations of each.

Preliminary results of a dose-finding study for botulinum toxin-A in patients with idiopathic overactive bladder: 100 versus 150 units.

AIMS: To evaluate the clinical outcomes of two different doses of BTX-A in patients with I-OAB. METHODS: This investigator initiated, randomized trial was designed to evaluate clinical differences in outcomes for 100 versus 150 U BTX-A in patients with I-OAB. Patients with OAB-Wet and OAB-Dry were randomized to receive 100 or 150 U BTX-A intra-detrusor injection. For patients with OAB-Wet, the primary outcome of interest was change in daily UUI episodes, and for those with OAB-Dry the primary outcome measure was change in number of daily voids as determined by 3-VD. Statistical comparisons were made both pre- and post-injection and also between different treatment groups to assess the superiority of one dose versus the other. RESULTS: Forty-four patients enrolled in the study; 10 OAB-Dry and 12 OAB-Wet patients received 100 U and another 10 OAB-Dry and 12 OAB-Wet patients received 150 U. No significant differences in outcome measure were noted between those receiving 100 versus 150 U. Patients with OAB-Wet tended to be completely dry more frequently if they received the 150 U dose, but this was not statistically significant. No differences in urodynamics outcomes were noted between the groups. QOL was significantly improved in both groups with no difference between the different doses. CONCLUSIONS: In patients with I-OAB, preliminary results indicate that 100 U BTX-A and 150 U BTX-A are equivalent in terms of symptom reduction and QOL improvement.

A historical perspective on cystocele repair--from honey to pessaries to anterior colporrhaphy: lessons from the past.

PURPOSE: Ancient reports of the treatment of anterior vaginal wall prolapse (cystocele) include the use of honey, astringents and even turning the woman upside down. Various objects were inserted into the vagina to correct this condition. These have since evolved to modern day pessaries. There is limited information on the historical surgical management of cystocele. In this review we provide a historical perspective on the treatment of cystocele. MATERIALS AND METHODS: A MEDLINE search was conducted using the words prolapse, cystocele, etiology, anatomy, pathophysiology, classification systems and the modifications in the nonsurgical and surgical techniques involved in cystocele repair. RESULTS: Development of pelvic surgery finds its roots in the Ebers papyrus (1550 BC) and evolved from Hippocrates (400 BC) who used pessaries with pomegranate to reduce uterine prolapse. Other maneuvers were also used. Vesalius was the first to provide a detailed description of the entire female genital tract. Adolf Retzius defined the boundaries of the prevesical space in 1849. The current concepts regarding the etiology of cystocele were proposed in 1912. Modern pelvic organ surgeons have modified these concepts to popularize new surgical approaches to this ancient clinical problem. CONCLUSIONS: These contributions provide a sound basis for future surgical developments.

Duloxetine compared with placebo for the treatment of women with mixed urinary incontinence.

AIMS: Evaluate duloxetine in the treatment of women with mixed urinary incontinence (MUI). MATERIALS AND METHODS: 588 women, 19-85 years old with >or=4 incontinence episodes/week were randomly assigned to duloxetine 80 mg/day (N = 300) or placebo (N = 288). Patients were classified into three symptom subgroups: stress or urge predominant MUI (SPMUI or UPMUI) or balanced MUI (BMUI) based on their responses to the validated Stress/Urge Incontinence Questionnaire. Half the population was randomly assigned to have urodynamics; SPMUI, UPMUI, and BMUI condition diagnoses were based on signs, symptoms, and urodynamic observations. The primary outcome measure was the change in incontinence episode frequency (IEF). Secondary outcome measures included the Incontinence Quality of Life (I-QOL) scores, the ICI Quality of Life (ICIQ-SF) score, and the Patient Global Impression of Improvement (PGI-I) rating. RESULTS: At baseline, women with SPMUI averaged 15.9 IEF/week (61% stress), those with UPMUI averaged 13.2 (70% urge), and those with BMUI averaged 16.5 (52% urge). Overall IEF decreases were significantly greater with duloxetine than placebo (median percent reduction 60% vs. 47%, P < 0.001); both UUI and SUI episodes were significantly decreased with duloxetine (median SUI IEF reduction 59% vs. 43%, P = 0.001; UUI IEF reduction 58% vs. 40%, P < 0.001). Duloxetine IEF decreases were significantly greater for patients with SPMUI conditions and symptoms and for those with UPMUI conditions but not symptoms. Significant benefits were also demonstrated with duloxetine for improvements in I-QOL total score (11.5 points vs. 8.1 points, P = 0.002), all three I-QOL subscale scores, and for the ICIQ-SF score (-2.6 vs. -1.7, P = 0.002) as well as for PGI-I ratings (much/very much better 44.2% vs. 27.3%, P = 0.001). CONCLUSION: Duloxetine demonstrated significant efficacy in this population of women with MUI.