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.

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.

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.

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.

Are mast cells still good biomarkers for bladder pain syndrome/interstitial cystitis?

PURPOSE: ESSIC identifies mast cell infiltrates of detrusor muscle as a diagnostic criterion for bladder pain syndrome/interstitial cystitis. However, an increased mast cell count is also characteristic of overactive bladder syndrome. The lack of uniformity in mast cell detection methods hampers data comparison. Using state-of-the-art techniques we investigated whether mast cells differ among bladder conditions. MATERIALS AND METHODS: We analyzed bladder biopsies from 56 patients, including 31 with bladder pain syndrome/interstitial cystitis with (12) or without (19) Hunner lesions, 13 with overactive bladder syndrome and 12 without bladder symptoms to determine the quantity, location, distribution and activation of mast cells using immunohistochemistry with anti-mast cell tryptase. Patients were allocated to study groups by key bladder symptoms commonly used to define conditions (pain and major urgency). RESULTS: Subepithelial mast cell localization (p <0.001) and an increased detrusor mast cell count (p = 0.029) were characteristic of bladder pain syndrome/interstitial cystitis with Hunner lesions. The optimal cutoff of 32 detrusor mast cells per mm(2) achieved only 68% accuracy with 38% positive predictive value. No difference was observed between bladder pain syndrome/interstitial cystitis without Hunner lesions and overactive bladder syndrome. Patient groups differed in lymphocyte infiltration (p = 0.001), nodular lymphocyte aggregates (p <0.001) and urothelium integrity (p <0.001). CONCLUSIONS: Subepithelial mast cell distribution was characteristic of bladder pain syndrome/interstitial cystitis with Hunner lesions. Detrusor mastocytosis had poor predictive value for bladder pain syndrome/interstitial cystitis. Mast cell assessment did not distinguish bladder pain syndrome/interstitial cystitis without Hunner lesions from overactive bladder syndrome.

Local immune response in bladder pain syndrome/interstitial cystitis ESSIC type 3C.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome/interstitial cystitis (BPS/IC) is identified based on subjective symptoms which lead to heterogeneous patient populations. Previous studies using gene expression arrays for BPS/IC with Hunner's lesions [European Society for the Study of Interstitial Cystitis (ESSIC) type 3C], a subtype of the condition discernible by cystoscopy, have revealed characteristic immune responses and urothelial abnormalities. This current study aimed to further characterize this subtype using a gene expression panel. We hypothesized that B-cell activation with high levels of urinary antibody concentration would be found. METHODS: Cold-cup bladder biopsies, catheterized urine and blood were collected from 15 BPS/IC ESSIC type 3C patients, 11 non-inflammatory overactive bladder (OAB) patients and eight healthy controls. Gene expression in biopsies was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry was performed on bladder tissue and urinary immunoglobulins G and A were quantified by enzyme-linked immunosorbent assay. Statistical analyses included the Kruskal-Wallis test for non-parametric data and post hoc tests identified differences between groups. RESULTS: High expression of T- and B-cell markers (CTLA4, CD20, CD79A, IGH@), low expression of urothelial markers (KRT20, UPK1B, UPK3A), focal lymphoid aggregates in the submucosa and high immunoglobulin concentration in urine were found exclusively in BPS/IC ESSIC type 3C patients. Results for OAB were in intermediate ranges between the other two groups and UPK1B even reached significantly lower expression when compared to healthy controls. CONCLUSIONS: BPS/IC ESSIC type 3C is characterized by a local adaptive immune response with elevated urinary antibody concentrations. Quantification of urinary immunoglobulin levels could be used for a non-invasive diagnosis of BPS/IC ESSIC type 3C.

Gene expression profile of bladder tissue of patients with ulcerative interstitial cystitis.

BACKGROUND: Interstitial cystitis (IC), a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. By cystoscopic examination, IC can be classified into an ulcerative and a non-ulcerative subtype. To better understand this debilitating disease on a molecular level, a comparative gene expression profile of bladder biopsies from patients with ulcerative IC and control patients has been performed. RESULTS: Gene expression profiles from bladder biopsies of five patients with ulcerative IC and six control patients were generated using Affymetrix GeneChip expression arrays (Affymetrix--GeneChip Human Genome U133 Plus 2.0). More than 31,000 of > 54,000 tested probe sets were present (detection p-value < 0.05). The difference between the two groups was significant for over 3,500 signals (t-test p-value < 0.01), and approximately 2,000 of the signals (corresponding to approximately 1,000 genes) showed an IC-to-healthy expression ratio greater than two. The IC pattern had similarities to patterns from immune system, lymphatic, and autoimmune diseases. The dominant biological processes were the immune and inflammatory responses. Many of the up-regulated genes were expressed in leukocytes, suggesting that leukocyte invasion into the bladder wall is a dominant feature of ulcerative IC. Histopathological data supported these findings. CONCLUSION: GeneChip expression arrays present a global picture of ulcerative IC and provide us with a series of marker genes characteristic for this subtype of the disease. Evaluation of biopsies from other bladder patients with similar symptoms (e.g. patients with non-ulcerative IC) will further indicate whether the data presented here will be valuable for the diagnosis of IC.