Current Treatment of Stress Urinary Incontinence by Bulking Agents and Laser Therapy-An Update.

Stress urinary incontinence (SUI) affects around 20% of women. In addition to the established suburethral sling insertion, two less invasive approaches are of interest today: urethral bulking agents and vaginal laser therapy. This review discusses articles through December 2023 identified by a PubMed literature search using the keywords "incontinence" and "bulking" or "laser". Although the two approaches are less effective than sling insertions, there are specific conditions in which one or the other technique is more advantageous. Injecting bulking agents into the urethra only takes some minutes and works without general anesthesia. The method is particularly suited for elderly, frail, or obese patients with multiple comorbidities, but is also applicable for all patients and in combination with other therapies. Generally, the safety profile is good but differs between bulking materials. Two laser types-the Erbium:YAG laser with SMOOTH-mode and the fractional ablative CO2 laser-deliver heat into the tissue to induce tissue tightening and regeneration. Intravaginal laser therapy improves mild to moderate SUI, while studies describe how intraurethral laser therapy is also beneficial for severe SUI. Young women between childbirths, as well as postmenopausal women, may benefit from laser therapy. The method is safe, can be performed on an outpatient basis, and does not require any artificial material.

Vaginal erbium laser treatment for stress urinary incontinence: A multicenter randomized sham-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of non-ablative vaginal Er:YAG laser device in stress urinary incontinence (SUI) treatment. METHODS: We conducted a multicenter blinded randomized sham-controlled trial in which women with urodynamic SUI were randomization to active arm using Er:YAG laser therapy, and sham arm using sham handpiece. Patients received two treatments 1 month apart. The primary outcomes measure was 1 h pad weight test measured at 6 months. Secondary outcomes were durability of treatment success at 12 months, and questionnaires for assessment of SUI severity (ICIQ-UI SF), sexual function (PISQ-12) and HRQoL (KHQ), and incidence and severity of device related adverse events and pain (VAS). RESULTS: A total of 110 participants with SUI were recruited; 73 in the active arm and 37 in the sham arm. Two participants were excluded; one was assigned the wrong treatment and one withdrew their consent. Treatment success was observed in 36% of the sham arm and 59% of the active arm; in the latter, odds of achieving treatment success were more than three-fold higher (OR 3.63, 95% CI: 1.3-11.2, P = 0.02). HRQoL by KHQ showed significant improvement in the active versus the sham arm (OR 0.36, 95% CI: 0.15-0.87, P = 0.003). Similarly, subjective patient assessment of general and sexual function improvement with PISQ-12 and PGI-I showed superior effect over sham (OR 2.8, 95% CI: 1.2-7.0, P = 0.02 and OR 0.13, 95% CI: 0.05-0.36, P < 0.001, respectively). CONCLUSION: Non-ablative vaginal Er:YAG laser therapy significantly improves SUI symptoms versus sham treatment. Er:YAG laser therapy should be considered as a non-surgical treatment option for SUI patients.

Nd:YAG/Er:YAG dual laser compared with topical steroid to treat vulvar lichen sclerosus: A randomised controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of a novel non-ablative Nd:YAG/Er:YAG dual laser treatment for vulvar lichen sclerosus (LS) in comparison with the recommended first-line therapy with topical steroid. DESIGN: A randomised investigator-initiated active-controlled trial. SETTING: Single tertiary referral centre. POPULATION: Women with vulvar LS. METHODS: Randomisation (2:1) to Nd:YAG/Er:YAG laser therapy or topical clobetasol proprionate therapy. Four laser treatments at 0, 1, 2 and 4 months or decreasing doses of steroid for 6 months. MAIN OUTCOME MEASURES: The primary outcome was the change in objective validated clinical LS score in the laser arm between baseline and 6 months. Secondary outcomes were laser tolerability/safety, symptom scores and patient satisfaction. RESULTS: Sixty-six women were included, 44 in the laser group and 22 in the steroid group. The total LS score decreased by -2.34 ± 1.20 (95% CI -2.71 to -1.98) in women treated with laser compared with a decrease of -0.95 ± 0.90 (95% CI -1.35 to -0.56) in those receiving steroid applications (p < 0.001). Laser treatment was safe and well tolerated. Subjective severity scores (on visual analogue scale) and vulvovaginal symptoms questionnaire scores improved similarly for the laser and steroid arms without significant differences between the two treatments. Patient satisfaction was higher in the laser arm than in the steroid arm (p = 0.035). CONCLUSIONS: Non-ablative dual Nd:YAG/Er:YAG laser therapy was safe and significantly improved clinical outcome and subjective symptoms at the 6-month follow up. This suggests that laser may be a promising alternative to corticosteroid therapy. However, the authors caution regular follow ups because of the premalignant nature of the disease.

Nd:YAG/Er:YAG dual laser vs. topical steroid to treat vulvar lichen sclerosus: study protocol of a randomized controlled trial.

PURPOSE: Vulvar lichen sclerosus (LS) is a chronic debilitating inflammatory skin disease. Today, the gold standard is a life-long topical steroid treatment. Alternative options are highly desired. We present a study protocol of a prospective, randomized, active-controlled, investigator-initiated clinical trial comparing a novel non-invasive dual Nd:YAG/Er:YAG laser therapy with the gold standard for the management of LS. METHODS: We recruited 66 patients, 44 in the laser arm and 22 in the steroid arm. Patients with a physician-administered clinical LS score ≥ 4 were included. Participants received either four laser treatments 1-2 months apart, or 6 months of topical steroid application. Follow-ups were planned at 6, 12, and 24 months. The primary outcome looks at the efficacy of the laser treatment at the 6-month follow-up. Secondary outcomes look at comparisons between baseline and follow-ups within the laser or the steroid arm, and comparisons between laser vs. steroid arm. Objective (LS score, histopathology, photo documentation) and subjective (Vulvovaginal Symptoms Questionnaire, symptom VAS score, patient satisfaction) measurements, tolerability, and adverse events are evaluated. CONCLUSION: The findings of this trial have the potential to offer a novel treatment option for LS. The standardized Nd:YAG/Er:YAG laser settings and the treatment regime are presented in this paper. CLINICAL TRIAL IDENTIFICATION NUMBER: NCT03926299.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 015/091, January 2022): Part 2 with Recommendations on Interventional/Surgical Therapy of Overactive Bladder, Surgical Treatment of Stress Urinary Incontinence and Diagnosis and Therapy of Iatrogenic Urogenital Fistula.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the surgical treatment of female patients with stress urinary incontinence and urge incontinence. Specific solutions for the diagnostic workup and treatment of uncomplicated and complicated urinary incontinence are discussed. The diagnostics and surgical treatment of iatrogenic urogenital fistula are presented.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/091, January 2022): Part 1 with Recommendations on Diagnostics and Conservative and Medical Treatment.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, etiology, classification, symptoms, diagnostics, and treatment of female patients with urinary incontinence. Specific solutions for the diagnostic workup and appropriate conservative and medical therapies for uncomplicated and complication urinary incontinence are discussed.

Combination therapy with botulinum toxin and bulking agent-An efficient, sustainable, and safe method to treat elderly women with mixed urinary incontinence.

AIMS: To evaluate the efficacy, sustainability and safety of combined botulinum toxin and polyacrylamide hydrogel (PAHG) therapy to treat urgency and stress components of therapy-refractory mixed urinary incontinence (MUI) in an elderly study population. METHODS: Fifty-five women with therapy-refractory MUI were treated with botulinum toxin and PAHG in one surgical procedure. Urgency urinary incontinence (UUI) and stress urinary incontinence (SUI) outcomes were separately assessed after 4 and 12 months by objective UUI episodes/24 h and cough test, subjective impact of UUI and SUI on quality of life, and subjective International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). MUI outcome was calculated by combining UUI and SUI outcomes. Complications were monitored throughout the study. RESULTS: At 4 months, objective cure rates were 73%, 53%, and 42%, and subjective cure rates were 71%, 52%, and 50% for SUI, UUI, and MUI. At 12 months, objective cure rates were 73%, 56%, 50% and subjective cure rates were 78%, 42%, and 40% for SUI, UUI, and MUI. The ICIQ-UI SF score decreased by 9.0 and 8.7 points after 4 and 12 months. All complications were transient and included 22% clean intermittent catheterization immediately after surgery, 33% postvoid residual volumes >100 ml at 14 days, and 13% symptomatic urinary tract infection within the first postoperative month. CONCLUSIONS: The combination of botulinum toxin and PAHG is effective, sustainable and safe to treat therapy-refractory MUI, even in an elderly and frail study population. Patients benefit from the short surgical procedure without the need for general anaesthesia or discontinuation of anticoagulation.

Erbium:YAG laser treatment of female stress urinary incontinence: midterm data.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is treated using intravaginal laser therapy. We wanted to find out how incontinence severity at baseline and the number of laser interventions affect success rate, and whether the effect of laser therapy was obvious 6 months and 2 years after the last laser intervention. METHODS: Fifty-nine women, 32 with SUI I, 16 with SUI II, and 11 with SUI III were treated using an erbium-doped yttrium aluminium garnet (Er:YAG) laser following the IncontiLase® protocol. Therapy included five laser sessions with a 1-month interval between sessions. Objective (1-h pad test) and subjective data (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form [ICIQ-UI SF], Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire [PISQ-12]) were assessed at baseline, after two and four laser sessions and 6 months and 2 years after the fifth laser session. RESULTS: Objective cure/improve rates for mild SUI I were 69%, 78%, 91%, and 78% after two, four, and five laser sessions at the 6-month and 2-year follow-ups. Subjective cure rates (ICIQ-UI SF) were 53%, 69%, 72%, and 66%, and sexual function (PISQ-12) also improved. For SUI II, objective cure/improve rates were 31%, 63%, 69%, and 50%. Subjective cure rate was 13% at the 2-year follow-up. For SUI III, only one patient had an objective improvement after two and four laser sessions. CONCLUSIONS: Intravaginal laser therapy led to cure/improvement for SUI I and SUI II, but not for severe SUI III. Outcome was better after four to five laser sessions than after two laser sessions. Follow-up data 6 months and 2 years after laser intervention showed sustainability of the treatment.

[Acute and recurrent urinary tract infections in women presenting in primary practice]. / Akute und rezidivierende Harnwegsinfekte der Frau in der allgemeinmedizinischen Praxis.

Acute and recurrent urinary tract infections in women presenting in primary practice Abstract. Acute and recurrent urinary tract infections in women of all age groups are becoming an increasing problem in primary care and medical practice. Symptoms can be relieved by a guideline-oriented acute therapy and a multimodal infection prophylaxis. The restoration of the body's natural defence mechanisms plays a central role. This article informs about the causes, the basic diagnostic examinations and the practical use of therapeutic and prophylactic measures.

Current Treatment Concepts for Stress Urinary Incontinence.

Initially, stress urinary incontinence should be treated by conservative measures, such as weight reduction, hormonal substitution, physiotherapy, pelvic floor exercise and/or the use of pessaries. Incontinence surgeries are only recommended in case of unsuccessful conservative therapy. Today, tension-free suburethral sling insertions represent the gold standard of incontinence surgery yielding very good outcomes (cure rates of 80­90 %). Pelvic-floor sonography provides important information on decision of surgical methods and the management of complications. Furthermore, intra- or paraurethral injection of bulking agents is a promising, minimally invasive surgical alternative. This article discusses treatment concepts, pre-, intra- and post-operative examinations, decision on surgical methods, operational details for surgical success, and the prevention and management of complications.

Re: Sheng W, Zhang H, Kirschner-Hermanns R. Could urinary nerve growth factor be a biomarker for overactive bladder? A meta-analysis. Neurourol Urodyn. 2017;9999:1-8. doi: 10.1002/nau.23210.

Sheng et al (Neurourology and Urodynamics 2017; DOI: 10.1002/nau.23210) presented a meta-analysis based on 17 publications to show that urinary nerve growth factor (NGF) may be a useful biomarker for overactive bladder syndrome (OAB). Unfortunately, 13 of the 17 studies used an unspecifc enzyme-linked immunosorbent assay (ELISA), the Promega NGF Emax Immunoassay, to quantify NGF in urine. This assay did not detect NGF in urine, but other urinary components, such as immunoglobulin G, and in 2014, it was withdrawn from the market. With other NGF-ELISAs, urinary NGF concentrations were found to be below detection level for both, OAB and healthy controls. Currently, ELISA techniques are not sensitive enough to detect NGF in urine, and urinary NGF cannot be used as a biomarker for OAB.

Role of intrinsic sphincter deficiency with and without urethral hypomobility on the outcome of tape insertion.

AIMS: Intrinsic sphincter deficiency (ISD) is a known risk factor for therapy failure after tension-free vaginal tape (TVT) insertion. The purpose of this study was to investigate if the severity of ISD alone or other factors such as urethral mobility and tape localization influence outcomes. METHODS: One hundred and nine women with urodynamically determined ISD, a TVT insertion, and a 6-month follow-up visit were included. Urethral length, mobility, and tape localization were evaluated by pelvic floor sonography. Patients were classified into three urethral mobility groups (hypomobile, normomobile, hypermobile). Surgical outcome was assessed by a combination of objective and subjective criteria. RESULTS: Therapeutic success rate after TVT insertion was 81.6%. The severity of ISD did not associate with therapy failure. But urethral mobility (P < 0.0001), relative tape position (P = 0.0003), and tape-urethra distance (P < 0.0001) differed between cured and not cured patient groups. Patients with a relative tape position toward 1/2 of urethral length had a higher cure rate. Significantly different cure rates (P = 0.0003) were found for hypomobile (67%), normomobile (76%), and hypermobile (100%) urethras. For ISD patients with a hypomobile urethra, highest cure rates were obtained for tape-urethra distances between 2.5 and 3.5 mm. CONCLUSIONS: The reduced cure rate for ISD patients was due to the subgroup with a hypomobile urethra. A prospective study is needed to confirm that slightly shorter tape-urethra distances and a relative tape position more toward the mid-urethra will lead to better outcomes for this patient group.

Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial.

BACKGROUND: Escherichia coli infections are increasing worldwide in community and hospital settings. The E coli O-antigen is a promising vaccine target. We aimed to assess the safety and immunogenicity of a bioconjugate vaccine containing the O-antigens of four E coli serotypes (ExPEC4V). METHODS: In this multicentre phase 1b, first-in-human, single-blind, placebo-controlled trial, we randomly assigned (1:1) healthy adult women with a history of recurrent urinary tract infection (UTI) to receive a single injection of either intramuscular ExPEC4V or placebo. The primary outcome was the incidence of adverse events among vaccine and placebo recipients throughout the study. Secondary outcomes included immunogenicity and antibody functionality, and the incidence of UTIs caused by E coli vaccine serotypes in each group. This study is registered with ClinicalTrials.gov, number NCT02289794. FINDINGS: Between Jan 20, 2014, and Aug 27, 2014, 93 women received target-dose ExPEC4V and 95 received placebo. The vaccine was well tolerated: no vaccine-related serious adverse events occurred. Overall, 56 (60%) target-dose vaccines and 47 (49%) placebo recipients experienced at least one adverse event that was possibly, probably, or certainly related to injection. Vaccination induced significant IgG responses for all serotypes: at day 30 compared with baseline, O1A titres were 4·6 times higher, O2 titres were 9·4 times higher, O6A titres were 4·9 times higher, and O25B titres were 5·9 times higher (overall p<0·0001). Immune responses persisted at 270 days but were lower than those at 30 days. Opsonophagocytic killing activity showed antibody functionality. No reduction in the incidence of UTIs with 103 or more colony-forming units per mL of vaccine-serotype E coli was noted in the vaccine compared with the placebo group (0·149 mean episodes vs 0·146 mean episodes; p=0·522). In post-hoc exploratory analyses of UTIs with higher bacterial counts (≥105 colony-forming units per mL), the number of vaccine serotype UTIs did not differ significantly between groups (0·046 mean episodes in the vaccine group vs 0·110 mean episodes in the placebo group; p=0·074). However, significantly fewer UTIs caused by E coli of any serotype were noted in the vaccine group compared with the placebo group (0·207 mean episodes vs 0·463 mean episodes; p=0·002). INTERPRETATION: This tetravalent E coli bioconjugate vaccine candidate was well tolerated and elicited functional antibody responses against all vaccine serotypes. Phase 2 studies have been initiated to confirm these findings. FUNDING: GlycoVaxyn, Janssen Vaccines.

Sensory Hyperinnervation Distinguishes Bladder Pain Syndrome/Interstitial Cystitis from Overactive Bladder Syndrome.

PURPOSE: Pain is the key symptom that distinguishes bladder pain syndrome/interstitial cystitis from overactive bladder syndrome but overlap occurs. To find a discriminating marker for these bladder diseases we examined sensory hyperinnervation and neurotrophin receptor expression in bladder biopsies as well as nerve growth factor levels in urine. MATERIALS AND METHODS: Bladder biopsies from patients with bladder pain syndrome/interstitial cystitis, including 12 with and 19 without Hunner lesions, 13 with overactive bladder syndrome and 12 healthy controls, were analyzed by immunohistochemistry with antibodies to the nerve cell marker PGP9.5 (neuron-specific protein gene product 9.5), p75NTR (p75 neurotrophin receptor), the B-lymphocyte marker CD20 and mast cell tryptase. Urinary nerve growth factor was quantified by enzyme-linked immunosorbent assay. RESULTS: Subepithelial sensory hyperinnervation on PGP9.5 staining had 97% sensitivity and 76% specificity, increased lymphocytic infiltration had 90% sensitivity and 80% specificity, and urothelial defects had 97% sensitivity and 76% specificity to distinguish bladder pain syndrome/interstitial cystitis with and without Hunner lesions from overactive bladder syndrome and healthy controls. Increased sensory innervation was associated with submucosal mast cell localization. Staining of p75NTR in basal urothelial cells was indicative of bladder pain syndrome/interstitial cystitis. Urinary nerve growth factor levels were below the detection level and did not differentiate bladder diseases from healthy controls. CONCLUSIONS: Sensory hyperinnervation and basal urothelial p75NTR staining together with assessment of inflammatory lymphocytes and urothelial integrity allow for the differentiation of bladder pain syndrome/interstitial cystitis and overactive bladder syndrome even in the absence of Hunner lesions. Furthermore, these histopathological criteria enable the identification of early disease stages or oligosymptomatic/asymptomatic cases and may permit timely treatment to prevent disease progress.

Urethral bulking for recurrent stress urinary incontinence after midurethral sling failure.

AIMS: To assess the effectiveness of a polyacrylamide hydrogel (PAHG; Bulkamid®) in treating recurrent stress urinary incontinence (SUI) following a previous midurethral sling (MUS) implant. METHODS: This observational study, conducted since 2009, included 60 patients with recurrent SUI or mixed urinary incontinence (MUI) after a previous MUS and who chose to be treated with PAHG. Objective and subjective outcomes were assessed at 1, 6, and 12 months after the initial injection. Patients were classified as cured based on a negative cough test (supine and standing) and <2 g urine on 1-hr pad test and a VAS score improved by ≥90%. Improved were those with the loss of only a few drops of urine during the cough test and 2-10 g urine on 1-hr pad test or a reduction >50% compared with preoperative urine loss and a VAS score improved by ≥75%. RESULTS: The volume of PAHG injected in the current study ranged from 1-3 ml. Cured/improved rates were 93.3% (56/60), 88.3% (53/60), and 83.6% (46/55) at 1, 6, and 12 months, respectively. Patients with MUI had a cured urgency urinary incontinence rate of 36.8%, 47.4%, and 38.9%, respectively. Voiding dysfunction rates were 13.3% (8/60), 8.3% (5/60), and 1.8% (1/55) at 1, 6, and 12 months and urinary tract infection rates were 5% (3/60), 11.7% (7/60), and 3.6% (2/55), respectively. Other adverse events were short-term and/or observed in <4% of patients. CONCLUSIONS: PAHG can be used to treat recurrent SUI after MUS failure with good outcome and low complication rates. Neurourol. Urodynam. 36:722-726, 2017. © 2016 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.