Skeletal Muscle-Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study.

BACKGROUND AND AIMS: Fecal incontinence (FI) improvement following injection of autologous skeletal muscle-derived cells has been previously suggested. This study aimed to test the efficacy and safety of said cells through a multicenter, placebo-controlled study, to determine an appropriate cell dose, and to delineate the target patient population that can most benefit from cell therapy. METHODS: Patients experiencing FI for at least 6 months were randomized to receive a cell-free medium or low or high dose of cells. All patients received pelvic floor electrical stimulation before and after treatment. Incontinence episode frequency (IEF), FI quality of life, FI burden assessed on a visual analog scale, Wexner score, and parameters reflecting anorectal physiological function were all assessed for up to 12 months. RESULTS: Cell therapy improved IEF, FI quality of life, and FI burden, reaching a preset level of statistical significance in IEF change compared with the control treatment. Post hoc exploratory analyses indicated that patients with limited FI duration and high IEF at baseline are most responsive to cells. Effects prevailed or increased in the high cell count group from 6 to 12 months but plateaued or diminished in the low cell count and control groups. Most physiological parameters remained unaltered. No unexpected adverse events were observed. CONCLUSIONS: Injection of a high dose of autologous skeletal muscle-derived cells followed by electrical stimulation significantly improved FI, particularly in patients with limited FI duration and high IEF at baseline, and could become a valuable tool for treatment of FI, subject to confirmatory phase 3 trial(s). (ClinicalTrialRegister.eu; EudraCT Number: 2010-021463-32).

Cucurbita pepo-Rhus aromatica-Humulus lupulus Combination Reduces Overactive Bladder Symptoms in Women - A Noninterventional Study.

This prospective, noninterventional, multicenter 12-wk study in women with overactive bladder investigated the effectiveness of Granu Fink femina, a herbal combination of seed oil from Uromedic pumpkin (cultivar of Cucurbita pepo), Rhus aromatica (fragrant sumach) bark extract, and Humulus lupulus (hop) cone extract in a clinical setting. Patients documented overactive bladder symptoms and quality of life using questionnaires as well as diaries recording day- and nighttime micturition frequencies, urine leakages during physical activity or at sneezing or coughing, and use of incontinence pads. The full analysis set included 117 women (age: 21 - 78 y). Urination frequency decreased significantly with improvement during daytime in 49, 71, and 77 (out of 99) patients and at night in 45, 63, and 70 (out of 100) patients after 1, 6, and 12 wk, respectively. The mean frequency of leakages and used pads decreased significantly from 0.9 leakages and 2.0 pads at baseline to 0.4 leakages and 1.4 pads after 12 wk. In all measured aspects of overactive bladder-related quality of life, (coping, concern, sleep, social), statistically significant improvement was reached after 1 wk, with further improvement at 6 and 12 wk. Ninety-nine percent of the physicians and 95.4% of the patients rated tolerability as "very good" or "good". Treatment with Granu Fink femina progressively improved overactive bladder symptoms and related quality of life with significant improvements already after 1 wk. Based on these effects and the observed excellent tolerability profile, Granu Fink femina may be considered a valuable therapeutic option for overactive bladder.

Paravaginal defect: A new classification of fascial and muscle tears in the paravaginal region.

The lateral support of the vaginal wall depends on the integrity of the paravaginal section of the visceral pelvic fascia, levator ani, and their connection. Various defects of the muscle and fascia can result in identical clinical findings-ie, the descent of the lateral vaginal sulcus. In this study, we created a realistic scheme for classifying paravaginal defects, based on the complex relationship of the pelvic fascia with the levator ani. Surgical observations, cadaver examinations, and a complex magnetic resonance imaging (MRI)-based 3-dimensional (3D) model were used to analyze the spatial relationships of normal and defective anatomy of the female pelvic floor. Descent of the lateral vaginal sulcus can result from a defect in the paravaginal visceral pelvic fascia, levator ani, or both. The fascial defect can be partial or complete, and the muscle defect can vary in location. A detailed illustrated classification is presented. We present a new model of the pathology that underlies a common clinical finding.

The MiniArc sling system in the treatment of female stress urinary incontinence.

AIMS: To assess the technical feasibility of a new mini-invasive sling procedure (MiniArc) and present short-term results in the treatment of female urinary incontinence. MATERIALS AND METHODS: A total of 97 women with mixed or stress urinary incontinence (SUI) were treated by placement of the new single-incision sling. Pelvic organ prolapse was graded using the POP-Q system (pelvic organ prolapse quantification system). Preoperative workup included urodynamic evaluation, cough stress test and introital ultrasound. Postoperatively, introital ultrasound was performed to determine residual urine and check tape position. Quality of life was measured using King's Health Questionnaire. A voiding diary and pad count served to verify the patients' subjective complaints. RESULTS: The MiniArc single-incision sling procedure was the initial intervention in 37 (38.2%) patients and the second intervention in 60 (61.7%) patients with recurrent incontinence. The cough stress test was negative in 79 (83.1%) women 6 weeks after the sling procedure and in 74 (77.8%) at 12 months. De novo urge occurred in 32 (36.8%) women. Quality of life was significantly improved at 12-month follow-up in 65 (69.1%) patients (p < 0.001). The number of pads decreased significantly from 2.2 to 0.6 (p < 0.001) after the procedure. One patient developed an hematoma and bladder perforation occurred in another. CONCLUSIONS: Our short-term clinical results suggest that the MiniArc is a safe and effective minimally invasive sling procedure for treating female SUI. Randomized comparative controlled trials and long-term results are still required to define the role of the new sling system in comparison to established mid-urethral tape techniques for treating incontinence.

MRI morphology of the levator ani muscle, endopelvic fascia, and urethra in women with stress urinary incontinence.

OBJECTIVE: To evaluate pathomorphologic changes of the levator ani muscle, endopelvic fascia, and urethra in women with stress urinary incontinence (SUI) by MRI. STUDY DESIGN: Fifty-four women with SUI were examined by MRI (1.5T): body phased-array coil, axial and coronal proton-density-weighted sequences. RESULTS: The urethral sphincter muscle showed a reduced thickness of its posterior portion (37%), an omega shape (13%) or higher signal intensity (50%); its abnormal configuration was associated with an increased signal intensity in 70% (p=0.001). The levator ani muscle comprised an unilateral loss of substance in 30%, a higher signal intensity in 28%, and altered origin in 19%. Central defects of the endopelvic fascia were present in 39% (n=21), lateral defects in 46%. There was a significant association between loss of the symphyseal concavity of the anterior vaginal wall and lateral fascial defects (p=0.001) and levator ani changes (p=0.016). CONCLUSION: MRI yields findings supporting current theories on the pathogenesis of SUI.

Uterine arterial embolization with tris-acryl gelatin microspheres: a histopathologic evaluation.

Uterine artery embolization (UAE) as an alternative to surgery for the treatment of uterine fibroids and adenomyosis uteri became increasingly popular. While the clinical success of this new treatment strategy is without doubt, there is still considerable uncertainty with respect to the morphologic changes induced by UAE. In this study, a total of 173 women were treated with UAE using tris-acryl gelatin microspheres (TGMS), a new particulate spherical embolic agent, for either symptomatic adenomyosis or leiomyoma. Surgical specimens of 8 women who underwent subsequent myomectomy or hysterectomy were evaluated by conventional histology and immunohistochemistry. TGMS were readily apparent in both macroscopy and routine histology. In patients with fibroids, TGMS accumulated in medium-sized vessels in the direct tumor vicinity, a minor fraction of particles was detected in the outer half of the myometrium and within leiomyomata. In patients with adenomyosis, a random distribution of TGMS was noted throughout the outer half of the myometrium. Freshly infused particles occluded the respective arteries without a significant tissue reaction. In the course of time, a granulomatous foreign body reaction in the vicinity of particles occurred, eventually followed by complete vessel destruction. Leiomyoma treated with UAE showed either hyaline necrosis, coagulative necrosis, or no change at all. Foci of adenomyosis remained unaltered. In conclusion, after UAE with TGMS, particles were identified predominately but not exclusively at the periphery of fibroids. Pathologists must be aware of the morphologic changes induced by UAE in leiomyoma to avoid misinterpretation of induced tissue alterations as signs of malignant tumor growth.

Vesicovaginal fistula after Irving sterilization: a case report.

BACKGROUND: Patients scheduled for gynecologic surgery must be informed about the development of urogenital fistulae as a possible complication. CASE: A 49-year-old woman underwent Irving sterilization with subsequent abdominal hysterectomy due to intraabdominal abscess formation. Inadvertent damage complication to the bladder during hysterectomy led to development of a vesicovaginal fistula despite intraoperative management. The fistula was repaired at once in a second session. As a sequela of bladder injury, the patient had recurrent vesical diverticula and urolithiasis with repeated removal of the diverticula and stones. A subsequent intervention performed laparoscopically led to development of a second vesicovaginal fistula. In addition, an anesthesia-induced complication resulted in cerebral hypoxia with postoperative development of Parkinson's disease. CONCLUSION: Retrospectively, there is doubt whether the proper surgical procedures were employed in this case. The fact that the patient had type 1 diabetes mellitus gives rise to the question of why no conservative method of contraception was chosen. The type of operative approach in elective surgery should always be planned on the basis of the individual patient's overall condition and in relation to the anatomic situation.

[Follow-up at 24 months after treatment of overactive bladder with 0.2 % sodium chondroitin sulfate]. / Zwei-Jahres-Follow-up nach Einsatz von 0,2 % Natrium-Chondroitinsulfat bei der Behandlung der "Uberaktiven Blase".

AIM: A retrospective study was performed to investigate whether the improvement of symptoms achieved with 0.2 % sodium chondroitin sulfate in treating overactive bladder (OAB) persists after 24 months. MATERIALS AND METHODS: Two years ago, a total of 82 patients with chronic OAB were randomly assigned to receive either anticholinergic treatment (Tolterodin; group A, n = 41) or 0.2 % sodium chondroitin sulfate (Gepan instill; group B, n = 41). Diagnostic assessment included a gynecological examination and history, urodynamic test-ing, introital ultrasound, and cystoscopy. Duration of treatment was 12 months. The patients underwent repeat follow-up after 24 months and the findings were compared with the results at 12 months. RESULTS: In group A, 15 / 35 (43 %) women reported an improvement of symptoms after 12 months as opposed to only 5 / 35 (14 %) after 24 months. In group B, there was an improvement in 23 / 32 (72 %) at 12 months and in 18 / 32 (56 %) after 24 months (p = 0.001). The subjective results were corroborated by means of urodynamic test-ing, pad counts, voiding frequency and nycturia (voiding diary). CONCLUSION: Our findings suggest that instillation treatment with 0.2 % sodium chondroitin sulfate results in a more sustained improvement or cure of the symptoms of overactive bladder due to development of a glycosaminoglycan layer. Long-term results are needed for confirmation.

Effect of vaginal polypropylene mesh implants on sexual function.

OBJECTIVE: Published studies report a very high rate of dyspareunia and impairment of sexual function in women who have undergone vaginal mesh repair. The present study investigates these problems with a view to sex therapy. STUDY DESIGN: A validated questionnaire was administered to 120 women to explore sex life before and after polypropylene mesh insertion (Apogee/Perigee). Postoperative exploration took place 1 year after surgery. In addition, gynecologic examinations were performed preoperatively and postoperatively to assess urogenital anatomy and function. RESULTS: Fifteen women reported dyspareunia before surgery, which was related to vaginal prolapse. No woman complained of dyspareunia at 1-year follow-up. In 40 patients (33.3%), analysis of the validated questionnaires revealed more deeply rooted sexual disorders based on partnership problems and unrelated to surgery. CONCLUSION: The results presented here show that vaginal mesh repair does not interfere with a healthy sex life. Our data on sexual function and activities suggests that sexuality is complex and cannot be reduced to mere genital aspects. Sexual dysfunction is only rarely associated with urogynecologic surgery.

Denial of pregnancy--characteristics of women at risk.

BACKGROUND: Denial of pregnancy is a woman's subjective lack of awareness of being pregnant. Denial throughout most of gestation or until delivery may be associated with significant risks for both mother and fetus. We wanted to investigate if maternal characteristics were useful in order to identify women at risk. METHODS: A 1-year prospective study was performed to recruit all women with denied pregnancies in Berlin, Germany. Maternal parameters were analysed and sociodemographic variables were compared with the regional birth register. RESULTS: Sixty-five women were recruited. Maternal age was between 15 and 44 years (median 27 years). Only 21 women had never been pregnant before. A large majority (83%) had a close partner. Three women had a psychiatric diagnosis of schizophrenia, and only one a current abuse of analgesics/tranquilizer. CONCLUSIONS: The group of women with denied pregnancy was heterogeneous, and a clear-cut typology of a 'pregnancy denier' could not be established.

Use of the 4F Rösch inferior mesenteric catheter in embolization procedures in the pelvis: a review of 300 cases.

The aim of this study is to evaluate the use of a 4F Rösch inferior mesenteric (RIM) catheter for pelvic embolization procedures. Between October 2000 and January 2006, 364 patients (357 female, 7 male; age: 23-67 years) underwent embolization of various pathologies [uterine fibroids (n = 324), pure adenomyosis of the uterus (n = 19), postpartum hemorrhage (n =1), traumatic or postoperative hemorrhage (n = 9), bleeding related to cervical cancer (n =7), AV malformation of the uterus (n = 2) and high-flow priapism (n = 2)] at a single institution. In all cases, bilateral catheterization was primarily attempted with the use of a 4F hook-shaped braided endhole catheter (Rösch-Inferior-Mesenteric, RIM-Catheter, Cordis, Miami, FL). Frequency of initial failure to catheterize the vascular territory of interest and carry out the embolization were recorded and the types of difficulty encountered were noted. Catheterization of the main stem of the vessel territory of interest with the use of a unilateral femoral approach and the 4F RIM catheter was successful in 334/364 (91.8%) the embolization cases. Bilateral catheterization of the internal iliac arteries using a single common femoral artery access and the 4F RIM catheter was achieved in 322/364 (88.5%) patients. In 12/364 (3.3%) patients, a contralateral puncture was performed and the same 4F catheter was used. In 28/364 (7.7%) cases the 4F RIM catheter was exchanged for a catheter with a cobra-shaped or sidewinder configuration. The 4F RIM catheter is a simple and valuable alternative to catheters and techniques commonly employed for pelvic artery embolization.

Clinical experience with urethral retro-resistance pressure measurement: a prospective pre- and postoperative evaluation in women with stress urinary incontinence.

AIMS: To identify possible correlations of urethral retro-resistance pressure (URP) with clinically and urodynamically proven stress urinary incontinence (SUI) and the outcome of anti-incontinence surgery. MATERIALS AND METHODS: URP was measured using the Monitorr system in women with clinically and urodynamically proven SUI without prolapse before and after anti-incontinence surgery (colposuspension n = 8, tension-free vaginal tape n = 6, tension-free transobturator tape n = 34). RESULTS: Forty-eight women (mean age 61.8 +/- 8.9 years) were evaluated preoperatively and on average 10 weeks postoperatively. Mean URP was 75.6 +/- 20.8 cm H(2)O preoperatively versus 75.4 +/- 17.9 cm H(2)O postoperatively (P = 0.898). The type of anti-incontinence surgery performed had no significant effect on postoperative URP. While no association was found between age and URP (P = 0.35), there was a positive correlation between URP and body mass index (BMI; r = 0.49, P = 0.0004). There was no correlation of URP with the preoperative pad test (P = 0.17) and urethral closure pressure at rest (P = 0.51). Finally, URP did not correlate significantly with the preserved length of the continence zone (0-1/3-2/3-3/3) as determined by the urethral stress profile (P = 0.37-0.72) or with the objective cure rate (negative pad test). CONCLUSIONS: Preoperative URP does not correlate with SUI in all women, has no predictive value, and does not correlate with the outcome of anti-incontinence surgery. However, there seems to be an association with biomechanical factors such as obesity, which may open up a new area of application for URP measurement in urogynecologic diagnosis.

Intra-operative introital ultrasound in Burch colposuspension reduces post-operative complications.

OBJECTIVE: To determine the effect of intra-operative monitoring of bladder neck elevation on cure rate and post-operative complications in patients undergoing colposuspension. DESIGN: Prospective, observational study. SETTING: Urogynaecology units, university hospitals. POPULATION: Ninety women operated on for genuine stress urinary incontinence. METHODS: The topography of the bladder neck and proximal urethra was assessed with pre-, intra- and post-operative introital ultrasound. These measurements were repeated during follow up for up to 48 months after surgery. Burch colposuspension of the bladder neck was performed under intra-operative introital ultrasound control, with reference to the patients' individual pre-operative ultrasound, to achieve a vertical height correction of 1-10 mm. MAIN OUTCOME MEASURES: Mid-term surgical outcome and post-operative complications. RESULTS: Ninety patients underwent colposuspension and 50 (56%) completed 48 months of follow up; 85 women (94%) were objectively continent at 12-month follow up and 42 of 50 (82%) at 48-month follow up. Surgical elevation of the bladder neck resulted in a median intra-operative elevation of 9 mm (7 mm at 48 months). All post-operative measurements demonstrated a significant decrease in linear dorsocaudal movement of the bladder neck during straining (P < 0.001). Funnelling and hypermobility were still decreased 48 months after incontinence surgery (P < 0.001). Voiding difficulty and urgency were uncommon and associated with evidence of funnelling and hypermobility. CONCLUSION: Intra-operative introital ultrasound standardises Burch colposuspension and thus might help to avoid overelevation and associated post-operative complications such as voiding difficulties and de novo urge incontinence without compromising the success of the operation.

The Miniarc® sling system in the treatment of female stress urinary incontinence

AIMS: To assess the technical feasibility of a new mini-invasive sling procedure (MiniArc®) and present short-term results in the treatment of female urinary incontinence. MATERIAL AND METHODS: A total of 97 women with mixed or stress urinary incontinence (SUI) were treated by placement of the new single-incision sling. Pelvic organ prolapse was graded using the POP-Q system (pelvic organ prolapse quantification system). Preoperative workup included urodynamic evaluation, cough stress test and introital ultrasound. Postoperatively, introital ultrasound was performed to determine residual urine and check tape position. Quality of life was measured using King's Health Questionnaire. A voiding diary and pad count served to verify the patients' subjective complaints. RESULTS: The MiniArc® single-incision sling procedure was the initial intervention in 37 (38.2 percent) patients and the second intervention in 60 (61.7 percent) patients with recurrent incontinence. The cough stress test was negative in 79 (83.1 percent) women 6 weeks after the sling procedure and in 74 (77.8 percent) at 12 months. De novo urge occurred in 32 (36.8 percent) women. Quality of life was significantly improved at 12-month follow-up in 65 (69.1 percent) patients (p < 0.001). The number of pads decreased significantly from 2.2 to 0.6 (p < 0.001) after the procedure. One patient developed an hematoma and bladder perforation occurred in another. CONCLUSIONS: Our short-term clinical results suggest that the MiniArc® is a safe and effective minimally invasive sling procedure for treating female SUI. Randomized comparative controlled trials and long-term results are still required to define the role of the new sling system in comparison to established mid-urethral tape techniques for treating incontinence.

Disintegration and stepwise expulsion of a large uterine leiomyoma with restoration of the uterine architecture after successful uterine fibroid embolization: case report.

Uterine fibroid embolization (UFE) is a new minimally-invasive treatment option for leiomyomata of the uterus leading to symptomatic improvement and shrinkage of the fibroids. We present a case of restoration of the uterine architecture after disintegration and stepwise expulsion of infarcted leiomyoma tissue 7 months after UFE for leiomyoma-related menorrhagia.

Postoperative funneling after anti-incontinence surgery--a prognostic indicator?--Part 1: colposuspension.

AIMS: How does funneling of the bladder neck after open colposuspension affect the postoperative cure rate? METHODS: In a retrospective study, 310 patients who underwent primary colposuspension for urodynamically proven genuine stress urinary incontinence were assessed by introital ultrasound before and immediately after surgery as well as at 6, 12, 24, 36, and 48 months. A total of 152 women completed 48-month follow-up. Objective cure rates at the different follow-up times were calculated and correlated with the presence of postoperative bladder neck funneling. RESULTS: The objective cure rate up to 6 months after colposuspension was 90.0 versus 76.8% up to 48-month follow-up. Urge symptoms occurred in 11.6% (36/310) of the women and de novo urge incontinence in 1.6% (5/310). Bladder neck funneling was significantly reduced after anti-incontinence surgery, from 55.2% before surgery to 12.3% (38/310) at 6-month follow-up (P < 0.0001). Postoperative funneling was associated with a higher recurrence rate. In the funneling group, 58.8 and 40.6% of the patients were continent up to 6 and 48 months, respectively, as opposed to 93.8 and 81.3% in the group without funneling (P < 0.0001). Urgency and de novo urge incontinence were more common in the funneling group (23.5 and 28.3% up to 6 and 48 months, respectively, vs. 12.7 and 13.5%; P < 0.05). CONCLUSIONS: Patients in whom funneling of the bladder neck diagnosed before surgery persists after colposuspension have a higher risk of recurrence and are more likely to develop postoperative complications.