SMAD2, SMAD3 and TGF-ß GENE expressions in women suffering from urge urinary incontinence and pelvic organ prolapse.

We evaluated the changes in the levels of TGF-ß and SMAD gene and protein expression in the uterosacral ligament (USL) of patients with concomitant pelvic organ prolapse (POP) and urgency urinary incontinence (UUI) to illuminate the pathophysiology of UUI. The TGF-ß pathway is involved in collagen synthesis and degradation. The Transforming Growth Family-ß (TGF-ß) superfamily has essential intracellular signaling components, such as newly identified SMAD family members. We evaluated the changes in the levels of TGF-ß and SMAD gene and protein expression in the USL of patients with concomitant pelvic organ prolapse (POP) and UUI. This study included 10 patients who had been diagnosed with POP and UUI in the study group and 14 asymptomatic women without complaints of POP and UUI in the control group. Biopsy samples were collected from bilateral USL tissues during vaginal or abdominal hysterectomy. Total RNA was extracted from USL tissue and analyzed by qPCR. The protein expression levels were also analyzed with ELISA. In UUI patients, SMAD3 and TGF-ß1 gene expression levels significantly decreased compared to the control patients (p = 0.008 and p = 0.006, respectively). SMAD2 mRNA levels did not differ between the study and control groups (p = 0.139). No differences was found in the levels of SMAD2, SMAD3, and TGF-ß1 protein expression between the two groups. The reduction in the gene and protein expression levels of SMAD3 and TGF-ß1 in women with UUI and lax uterosacral ligaments may indicate a causal link.Clinical trial registration: NCT04525105.

Urinary and fecal incontinence in patients with advanced ovarian cancer treated with CRS + HIPEC.

PURPOSE: The objective of this work was to analyze the long-term prevalence of urinary and fecal incontinence and their impact on quality of life in patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (CRS + HIPEC). METHODS: This cross-sectional study included a series of patients with advanced and recurrent ovarian cancer treated by CRS + HIPEC, with a disease-free period of at least 12 months after the procedure. Urinary incontinence was evaluated using the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), fecal incontinence using the Wexner test and the Fecal Incontinence Quality of Life (FIQL) questionnaire and global quality of life using the Short Form 36 (SF-36) survey. RESULTS: A total of 64 patients were included in the study, with a median age of 55 years (range 28-78). The urinary incontinence rate was 45% and the fecal incontinence rate was 20%. Up to 14% of the patients presented both types of incontinence. The presence of urinary or fecal incontinence generated a significant negative impact on quality of life in relation to patients without incontinence. DISCUSSION: Urinary and fecal incontinence is frequent in the follow-up of ovarian cancer patients treated with CRS + HIPEC. Reconsidering the approach to the pelvis without peritoneal metastases in the peritoneum could modify the incidence of these pelvic floor dysfunctions.

Vitamin D intake and the 10-year risk of urgency urinary incontinence in women.

Evidence indicates that higher serum 25-hydroxy vitamin D levels may be associated with decreased prevalence of urgency urinary incontinence (UI), but the impact of vitamin D consumption on development of urgency and mixed UI is unclear. The objective was to assess whether greater vitamin D intake was associated with decreased risk of incident urgency and mixed UI over 10 years using 2 large prospective cohorts of middle-aged and older women. We analyzed 38,101 women from the Nurses' Health Study I (NHS I) and 35,190 women from NHS II who were free of UI at baseline. We followed incident UI, defined as new UI occurring at least monthly, separately by subtype (urgency, mixed, stress UI), from 2002-2012. We categorized vitamin D intake from supplements and diet. We estimated relative risk for developing UI according to vitamin D intake using Cox-proportional hazard models with adjustment for covariates. Median vitamin D intake was 580IU in the older women in NHS I (age range 56-71 at baseline) and 487IU in middle-aged women in NHS II (age range 40-57). Among women taking ≥1000IU of vitamin D, median intake in the older women was 1252IU and 1202IU in the middle-aged women. Among the older women, we found no relation of vitamin D intake to risk of developing UI, across all UI subtypes. In multivariable-adjusted analysis for middle-aged women, the relative risk of developing mixed UI among women taking >1000IU was 0.79 (0.63, 0.99) and for urgency UI was 0.88 (0.71, 1.07), versus <200IU. Risks of developing stress UI were not related to vitamin D intake categories. Overall, we did not find a relationship between vitamin D intake and UI incidence in middle-aged and older women; however, the reported intake was moderate.

Pelvic floor muscle displacement during jumps in continent and incontinent women: An exploratory study.

INTRODUCTION: The prevalence of stress urinary incontinence during high-impact activities is high. Enhanced comprehension of pelvic floor muscle (PFM) displacement and activity is clinically relevant for the development of specific approaches in rehabilitation. The aim of the study is to investigate and to compare PFM displacement between the continent and incontinent women during jumps. METHODS: A cross-sectional, exploratory design was applied to investigate PFM displacement during drop jumps (DJ) and countermovement jumps (CMJ). PFM displacement was assessed in craniocaudal translation and forward-backward rotation with an electromagnetic tracking system. RESULTS: Twenty-eight continent and 22 incontinent women were included. During the first landing of DJ, a primary caudal, during the second landing of DJ/CMJ a primary cranial translation and during all jump a primary backward rotation was observed. No significant difference between the groups was found. DISCUSSION: PFM displacement during running demonstrated caudal translation/forward rotation before and cranial translation/backward rotation after heel strike. During the second landing of DJ/CMJ a cranial translation/backward rotation and during the first landing of DJ a caudal translation/backward rotation has been observed after ground contact. This may be due to the longer lasting bodyweight force in the first landing of DJ. No eccentric-concentric stretch-shortening cycle could be seen. CONCLUSION: This study indicates that during jumps two opposite reactions of involuntary PFM displacement happen, but no stretch-shortening cycle with an eccentric-concentric contraction could be found. Jumping stimuli inducing involuntary PFM displacement should be used for future investigations to consider a beneficial effect concerning continence.

Change in urinary storage symptoms following treatment for female stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Sling surgery is common for stress urinary incontinence (SUI). Yet many women have stress-predominant mixed urinary incontinence (MUI). The change in urgency/urge urinary incontinence (U/UUI) following treatment is not well documented. Our aim was to assess changes in U/UUI in women undergoing a sling placement for MUI and correlate this with improvement in quality of life (QOL). METHODS: This was a retrospective review of women treated for SUI with either an autologous rectus fascia pubovaginal sling (AF-PVS) or synthetic retropubic midurethral sling (MUS). Validated questionnaires-Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7), and visual analog scale (VAS) were obtained pre- and postoperatively. The independent association between change in storage symptoms and subjective cure-as defined by improved overall score on UDI-6, VAS score ≥ 7, or both -were assessed using multivariate logistic regression. RESULTS: Nine hundred and twenty-seven women were identified for inclusion; 718 (77.5 %) had preoperative MUI, of whom 487 (67.8 %) received an MUS and 231 (32.2 %) an AF-PVS. Similar objective cure rates were noted following MUS vs. AF-PVS (78.2 % vs. 71.9 %, p = 0.315). Subjectively, women treated with MUS experienced greater improvement in U/UUI (72.8 % vs. 57.6 %, p = <0.001) than AF-PVS. Multivariate analysis showed MUS patients were more than twice as likely to show subjective improvement in UDI-6 and VAS scores than the AF-PVS cohort. Postoperatively, validated questionnaires were significantly associated with storage symptom outcome. CONCLUSIONS: Patients with U/UUI experience significant symptom improvement following treatment for MUI. QoL assessment following surgery is directly correlated with improvement in U/UUI.

Differences in pelvic floor morphology between continent, stress urinary incontinent, and mixed urinary incontinent elderly women: An MRI study.

AIMS: To compare magnetic resonance imaging (MRI) of the pelvic floor musculature (PFM), bladder neck and urethral sphincter morphology under three conditions (rest, PFM maximal voluntary contraction (MVC), and straining) in older women with symptoms of stress (SUI) or mixed urinary incontinence (MUI) or without incontinence. METHODS: This 2008-2012 exploratory observational cohort study was conducted with community-dwelling women aged 60 and over. Sixty six women (22 per group), mean age of 67.7 ± 5.2 years, participated in the study. A 3 T MRI examination was conducted under three conditions: rest, PFM MVC, and straining. ANOVA or Kruskal-Wallis tests (data not normally distributed) were conducted, with Bonferroni correction, to compare anatomical measurements between groups. RESULTS: Women with MUI symptoms had a lower PFM resting position (M-Line P = 0.010 and PC/H-line angle P = 0.026) and lower pelvic organ support (urethrovesical junction height P = 0.013) than both continent and SUI women. Women with SUI symptoms were more likely to exhibit bladder neck funneling and a larger posterior urethrovesical angle at rest than both continent and MUI women (P = 0.026 and P = 0.008, respectively). There were no significant differences between groups on PFM MVC or straining. CONCLUSIONS: Women with SUI and MUI symptoms present different morphological defects at rest. These observations emphasize the need to tailor UI interventions to specific pelvic floor defects and UI type in older women. PATIENT SUMMARY: Older women with UI demonstrate different problems with their pelvic organ support structures depending on the type of UI. These new findings should be taken into consideration for future research into developing new treatment strategies for UI in older women. Neurourol. Urodynam. 35:515-521, 2016. © 2015 Wiley Periodicals, Inc.

Clinical findings associated with bladder trabeculations in women.

INTRODUCTION AND HYPOTHESIS: This study evaluated whether bladder trabeculations are associated with advanced prolapse, urinary urgency, or detrusor overactivity among women undergoing office cystoscopy. It is well established that bladder trabeculations are associated with bladder outlet obstruction (BOO) in men; however, the clinical significance of trabeculations in women is unclear. Whereas an analogous relationship has been proposed between prostatic obstruction in men and advanced pelvic organ prolapse (POP) in women, little data in the medical literature supports this theory. METHODS: A retrospective cohort study was conducted using Current Procedural Terminology (CPT) codes (52000, 52204) to identify all women who underwent office cystoscopy at our urogynecology center between January 2008 and May 2011. The 551 women identified were grouped by the presence or absence of bladder trabeculations. Multivariable logistic regression was used to estimate the association between trabeculations and the primary aim, increasing stage of prolapse, and the secondary aims: bladder outlet obstruction, detrusor overactivity, or urge urinary incontinence (UUI). RESULTS: Of the 551 women meeting inclusion criteria, 86 had trabeculations. Controlling for age, the odds of bladder trabeculations were eightfold greater for women with stage IV POP when compared with women with stage 0 prolapse [odds ratio (OR) 8.2, 95% confidence interval (CI) 1.6-43.1]. The odds of bladder trabeculations were twofold greater for women with detrusor overactivity (OR 2.3, 95% CI 1.3-4.0) found on urodynamic study and also as reflected subjectively by answers to Pelvic Floor Distress Inventory (PFDI) item number 16 (OR 4.2, 95% CI 1.3-14.5). CONCLUSION: In this study, bladder trabeculations were associated with stage IV prolapse in the anterior compartment as well as with detrusor overactivity and UUI.

The effect of solifenacin on urethral sphincter morphology.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to determine whether a 6-week course of 5 mg of solifenacin succinate used to treat mixed incontinence, produces measurable changes in the appearance of the urethral sphincter. METHODS: Twenty-six women undergoing treatment for mixed incontinence were recruited from a urogynaecology unit after failing to improve with conservative treatments and bladder drill. All underwent dual channel subtracted cystometry, which showed mixed urodynamic stress incontinence and detrusor overactivity. All patients underwent a 3D transperineal ultrasound before solifenacin therapy was started and after 6 weeks of treatment. The urethral length, width and volume of the smooth muscle and total sphincter volume were compared before and after the treatment. RESULTS: Clinically, 13 reported no improvement in either stress or urge incontinence. Eight women reported improvement in their urgency symptoms but no benefit in their stress leakage. Four women reported resolution of both stress and urge incontinence. One woman reported worsening of her bladder symptoms. There was no significant change in the urethral length (p = 0.27), width (p = 0.50), volume of smooth muscle (p = 0.87) or total sphincter volume (p = 0.60) before and after treatment with solifenacin. CONCLUSIONS: A 6-week course of solifenacin resulted in no measurable changes in the appearance of the urethral sphincter.

Sonographic basal ganglia alterations are related to non-motor symptoms in multiple sclerosis.

The anatomical basis of cognitive dysfunction and other non-motor symptoms in multiple sclerosis (MS) is poorly understood. In MS patients, transcranial sonography (TCS) shows neurodegenerative disease-like lesions of the substantia nigra (SN) and basal ganglia, thought to reflect iron accumulation. The present study deals with the question of whether sonographic changes of SN, brainstem raphe, lenticular nucleus (LN) or caudate nucleus are related to non-motor symptoms of MS. We used TCS to investigate 54 MS patients and 54 age- and sex-matched healthy subjects. Degree of cognitive (executive) dysfunction, fatigue, depression, and urinary urge incontinence in MS patients was assessed using the Paced Auditory Serial Addition Test, the Faces Symbol Test, the Modified Fatigue Impact Scale, the Beck Depression Inventory, and the Urinary Distress Inventory. Abnormal TCS findings of SN, brainstem raphe, LN, and caudate nucleus were found in 13, 7, 11, and 6% of the healthy subjects, but in 54, 43, 62, and 41% (each, p < 0.001) of the MS patients, with similar frequency in relapsing-remitting and primary or secondary progressive MS patients. Sonographic alteration of the LN correlated with cognitive dysfunction. Combined alteration of both, LN and SN, was clearly associated with cognitive dysfunction and cognitive fatigue. The combined sonographic alteration of SN and brainstem raphe indicated severe urinary urge incontinence irrespective of the presence of spinal MS lesions. No relation was found between depression and any of the TCS findings. These findings suggest that neurodegenerative processes affecting deep brain structures contribute to cognitive and autonomic dysfunction in MS.

Does the presenting bladder volume at urodynamics have any diagnostic relevance?

The aim of this study is to assess the diagnostic relevance of the presenting bladder volume (PBV) at urodynamics in women. Its measurement is most accurately made by adding the voided volume at uroflowmetry and the postvoid residual. The study involved 1,140 women presenting for their initial urogynecological assessment. Multivariate analysis of the relationships between high or low PBVs and different clinical and urodynamic variables. Median PBV was 174 mL. In overall terms, women with lower PBVs (0-174 mL) are significantly more likely to be older, of lower parity (0-1), have the symptom of nocturia, and the final diagnoses of sensory urgency and detrusor overactivity. These women are significantly less likely to have posterior vaginal and apical vaginal prolapse. Women with higher PBVs (over 174 mL) are significantly less likely to have either bladder storage diagnoses. The relatively low median PBV might reduce the demonstration of clinical stress leakage and restrict the interpretation of uroflowmetry data.

Urinary incontinence-assessment in women: stress, urge or both?

BACKGROUND: The aims of assessing urinary incontinence in women are to define the diagnosis, exclude other pathology and guide management. Treatment can be initiated when urinary incontinence is categorised as stress, urge or mixed incontinence. Once conservative measures have been exhausted, the management of stress incontinence is largely surgical, while that of urge urinary incontinence is largely medical. OBJECTIVE: This article discusses the clinical assessment of urinary incontinence in women with emphasis on the primary care assessment and indications for specialist referral. DISCUSSION: History taking is the cornerstone of urinary incontinence assessment and in combination with physical examination allows categorisation of patients into stress, urge or mixed urinary incontinence. Basic assessment includes investigations such as urine testing, bladder residual volume measurement, and a bladder diary. Urodynamic testing is not required in all patients or before initiating conservative treatment. Indications for specialist referral and urodynamic testing are discussed.

Urinary incontinence in women: variation in prevalence estimates and risk factors.

OBJECTIVE: To understand variation in prevalence of urinary incontinence (UI) and risk factors, given different definitions. METHODS: The National Health and Nutrition Examination Survey 2001-2002 data on UI were used. Prevalence, severity, and associated risk factors of stress, urge, mixed, and any UI were estimated in 2,875 adult women. Severe UI was defined as incontinence a few times or more per week. Moderate UI was defined as an incontinence frequency of a few times per month only, and mild UI was defined as incontinence frequency of a few times per year only. Odds ratios for the association of potential risk factors were examined in a logistic regression model. RESULTS: The overall prevalence of stress, urge, mixed, and any UI was 23.7%, 9.9%, 14.5%, and 49.2%, respectively. Prevalence of stress UI peaked at the fifth decade. Prevalence of urge and mixed UI increased with age. The largest number of risk factors and the strongest associations were found with severe UI. Age, ethnic background, and weight were significant risk factors common to all UI severity levels. Although parity and hysterectomy were risk factors for moderate and severe UI, they were not for mild UI. CONCLUSION: Prevalence of UI varies substantially by type and case definition. The stronger associations of known risk factors with severe UI and the lack of risk factors with lesser UI severity types suggest that severe UI includes primarily clinically significant cases, whereas mild UI represents transient or nonpathologic states that may not be clinically significant. LEVEL OF EVIDENCE: III.

Cystocoele and sensory urgency--our experience.

Sensory urgency appears mostly in patients with a specific or non specific cystitis, interstitial cystitis, intravesical foreign bodies, bladder carcinoma and carcinoma of the prostate, infravesical obstruction, estrogen deficiency and in some neurologic and psychiatric diseases. The aim of this study was to analyze and explain the relation between vaginal vault prolapse and sensory urgency. Clinical courses of 64 patients with cystocoele, which between 1999 and January 2006 have been treated on the Clinic of urology, University Hospital, Rijeka, Croatia, were analyzed retrospectively. On physical examination, using the International Society for Continence staging system we found that 4 (0.6%) had grade II, 29 (45.3%) had grade III, and 31 (48.4%) had grade IV cystocoele. Forty-seven (73.4%) women had urgency, for minimally 6 months to many years before the vaginal vault prolapse manifestation. In all but 3 (4.6%) an extended anterior vaginal colporaphy has been done, with only 1 (1.6%) recurrence of cystocele. It seems that sensory urgency may in fact be a predictor of cystocele.

A mouse model of simulated birth trauma induced stress urinary incontinence.

AIMS: To facilitate future applications of transgenic or knockout technologies in studies of simulated birth trauma induced stress urinary incontinence (SUI), we aimed to create a mouse model of SUI and explore the possible pathogenesis of this condition. METHODS: Thirty female C57BL/6 mice were randomly distributed into five groups. Four groups underwent vaginal distention (VD) for 1 hr, using a modified 6-Fr. Foley catheter with a balloon dilated to 0.3, 0.2, or 0.1 ml or sham distention. Four days after VD, all mice underwent leak-point pressure (LPP) measurement via an implanted suprapubic tube (SPT). The normal control group only had SPT placement and LPP measurement. After sacrifice, the urethras of the mice were harvested for routine histological examination and nerve staining. RESULTS: LPPs were significantly lower in groups after VD with 0.3- or 0.2-ml balloon than in control and sham distention groups (10.29 +/- 6.70, 14.65 +/- 6.51, 37.78 +/- 5.10, and 30.30 +/- 5.30 cm H(2)O, respectively). There were no significant differences in LPP between control and sham groups. Histology showed no significant differences in urethral striated muscle among the five groups. The density of immunoreactive neurofilaments in the urethra decreased after VD with 0.3- or 0.2-ml balloon. CONCLUSION: As a model of birth trauma, VD can induce SUI in female mice, the severity of which is related to intravaginal balloon size. Partial urethral denervation plays a plausible role in the pathogenesis of SUI. This novel mouse model could be used for further mechanistic studies of female SUI.

[New methods of patient selection for improved anticholinergic therapy]. / Neue Verfahren der optimalen Patientenselektion für die anticholinerge Therapie.

BACKGROUND: M3-specific inhibitors are currently preferred for anticholinergic therapy of OAB. However, not all of the patients profit from this regimen. This might reflect a heterogeneity of the patient group. The aim of this work is to define subgroups of patients with specific alterations of receptor expression and to profile the receptor expression individually. These receptor profiles might be used for the development of evidence-based "tailored" therapies. PATIENTS AND METHODS: Detrusor probes from bladder carcinoma patients (BCa, n=9 F, n=7 male) and interstitial cystitis patients (IC, n=9 female) were examined using confocal immunofluorescence and PCR. RESULTS: M2, M3, P2X1-3, and H1-3 mRNAs were demonstrated in detrusor tissue. As revealed by immunofluorescence, the M2 receptor expression was significantly higher in female compared to male BCa tissues. In addition, the M2 receptor was further upregulated in IC vs BCa in female detrusor. CONCLUSIONS: IC patients showed specific alterations of their receptor profile. Individual receptor profiles might be used to optimize medicinal therapies.

[Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions]. / Struktur und Funktion der suburothelialen Myofibroblasten in der humanen Harnblase unter normalen und pathologischen Bedingungen.

BACKGROUND: Myofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders. PATIENTS AND METHODS: Bladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells. RESULTS: Myofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes. CONCLUSIONS: Upregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the etiology of urge incontinence. A multi-step model is presented as a working hypothesis.