Marie Westergren Söderberg

Influence of different sling materials on connective tissue metabolism in stress urinary incontinent women.

Abstract: The aim of this study was to investigate the influence on the paraurethral connective tissue of different sling materials used in incontinence surgery. Biopsies from the paraurethral connective tissue were obtained intraoperatively from 16 women with stress urinary incontinence; all were operated on with the TVT procedure, 6 with Mersilene as the sling material and 10 with Prolene. Biopsies from 4 continent women with uterine bleeding irregularities, matched for age and parity, served as controls. New biopsies were obtained from all women after 2 years. The biopsies were examined histologically and analyzed for collagen concentration and solubility. An obvious inflammatory reaction with a significant increase in collagen extractability by pepsin was identified in patients where Mersilene was used as the sling material. A minimal inflammatory reaction without a significant change in collagen solubility was found in the Prolene group. In the control group no inflammatory reaction was seen. Mersilene gave rise to a significant foreign-body reaction in the paraurethral connective tissue after surgery. Such a reaction was not found with Prolene.

Young women with genital prolapse have a low collagen concentration

Background.  Genital prolapse is a common and handicapping form of pelvic floor dysfunction. To explain its genesis as a result of endopelvic connective tissue weakness, the collagen state was analyzed in women with and without genital prolapse.

Pelvic floor sex steroid hormone receptors, distribution and expression in pre- and postmenopausal stress urinary incontinent women

Background. Hormonal influence on stress urinary incontinence (SUI) is under debate. Sex steroid hormonal activity is mediated by nuclear receptor proteins. The aim of this study is to identify receptor isoforms and their genetic expression in the pelvic floor extra cellular matrix (ECM), and to compare women with and without SUI before and after menopause. Methods. Sub‐mucosal para‐urethral biopsies from 4 pre‐menopausal and 8 postmenopausal patients with SUI were analysed immunohistochemically regarding estrogen receptors (ER) α and β, the progesterone receptor (PR) (A+B) and B, and the androgen receptor (AR). Six pre‐menopausal and 5 postmenopausal women served as controls. All receptors were scored manually. Additionally, ER‐α and ER‐β were quantified by image analysis. Biopsies from 7 pre‐menopausal and 7 postmenopausal women suffering from SUI were studied by real‐time RT‐PCR for expression of ER‐α, ER‐β, PR and AR. The control group consisted of 5 pre‐menopausal and 5 postmenopausal women. Results. Immunohistochemistry revealed receptor‐positive cells for all isoforms in all groups. Higher ER‐β scores were seen in the pre‐menopausal SUI group compared to controls. Lower PR‐B scores were found after menopause in both groups. The image analysis confirmed that ER‐β was significantly increased in the pre‐menopausal SUI group compared to controls (p = 0.02). By real‐time RT‐PCR, no difference of mRNA expression regarding any receptor was detected between any SUI and control group. ER‐β mRNA levels were low or undetectable. There was a significant down‐regulation of PR among postmenopausal women (p = 0.001). Conclusions. The para‐urethral ECM is a target for sex steroid hormones mediated by the respective receptor. The significant higher expression of ER‐β protein in the pre‐menopausal SUI‐group was not reflected by a corresponding up‐regulation of mRNA which was poorly expressed in all groups.

Gene expressions of small leucine-rich repeat proteoglycans and fibulin-5 are decreased in pelvic organ prolapse

Few studies are performed on the sustainability of the pelvic floor extracellular matrix important for preventing development of pelvic organ prolapse (POP). Collagens I and III, the elastin-associated proteins fibrillin-1 and fibulin-5 and the small leucine-rich repeat proteoglycans (SLRPs) decorin, lumican and fibromodulin are involved in giving the tissue its mechanical properties. Para-urethral biopsies were obtained from 15 women, 6 pre- and 9 post-menopausal, with POP. Real-time reverse transcription-polymerase chain reaction and immunohistochemistry for collagen I, collagen III, fibrillin-1, fibulin-5, decorin, lumican and fibromodulin were performed and compared with 14 controls, 8 pre- and 6 post-menopausal. Statistical comparisons controlled for age changes in gene expressions. A 16-fold decrease in decorin mRNA expression, P = 0.0001, and 8-fold in lumican mRNA expression, P = 0.001, were discovered in premenopausal POP compared with matched controls. In all women with POP, there were lower gene expressions of fibromodulin, P = 0.004, and fibulin-5, P = 0.001, compared with all controls. All proteins were detectable by immunohistochemistry, showing a weaker staining for decorin in premenopausal POP. For the first time, we show substantially decreased gene signal for production of SLRPs, regulators of collagen fiber assembly and impairment in elastic fiber assembly by down-regulation of fibulin-5 in POP.

Decreased gene expression of fibrillin-1 in stress urinary incontinence†‡

Studies to show impairments in the pelvic floor extracellular matrix (ECM) associated with stress urinary incontinence (SUI) has earlier been performed, but the results are contradictory. Collagen I and III, the elastin associated proteins fibrillin‐1 and fibulin‐5 and the small leucine‐rich repeat proteoglycans (SLRPs) decorin, lumican and fibromodulin are involved in giving the tissue its mechanical properties. Their gene signals and tissue localizations were investigated.

New concepts and trends in vaginal prolapse surgery

Despite poor results in prolapse surgery, the operative procedures have basically remained unchanged for 100 years. It has been postulated that lifting restrictions and other measures of inactivation are crucial for the success. Even though most of what is done in prolapse repair is not evidence based, few have challenged the prevailing concepts. However, tradition‐based policies are now being scrutinized and in accordance with other operations, time of hospitalization is sharply reduced at many institutions. The reintroduction of local anesthesia and sedation offers potential advantages compared to regional‐ or general anesthesia. Although augmentation by foreign material is not altogether a new concept, the introduction of commercial kits make mesh procedures more standardized, but not necessarily technically more easy to perform. As molecular biology provides more and more evidence about the importance of the quality of the connective tissue, it is conceivable that foreign material in prolapse repair is here to stay. In this period of time it is more essential than ever to scientifically document the results of the new concepts. In the Nordic countries, where the first registries were set up for Tensionfree Vaginal Tape (TVT), a cooperative effort among 53 institutions is under way to evaluate mesh repairs in prolapse surgery.