RETRACTED ARTICLE: Transurethral ultrasonography-guided injection of adult autologous stem cells versus transurethral endoscopic injection of collagen in treatment of urinary incontinence

In the last years preclinical studies have paved the way for the use of adult muscle derived stem cells for reconstruction of the lower urinary tract. Between September 2002 and October 2004, 42 women and 21 men suffering from urinary stress incontinence (age 36–84 years) were recruited and subsequently treated with transurethral ultrasonography-guided injections of autologous myoblasts and fibroblasts obtained from skeletal muscle biopsies. The fibroblasts were injected into the urethral submucosa, while the myoblasts were implanted into the rhabdosphincter. In parallel, 7 men and 21 women (age 39–83 years) also diagnosed with urinary stress incontinence were treated with standard transurethral endoscopic injections of collagen. Patients were randomly assigned to both groups. After a follow-up of 12 months incontinence was cured in 39 women and 11 men after injection of autologous myoblasts and fibroblasts. Mean quality of life score (51.38 preoperatively, 104.06 postoperatively), thickness of urethra and rhabdosphincter (2.103 mm preoperatively, 3.303 mm postoperatively) as well as contractility of the rhabdosphincter (0.56 mm preoperatively, 1.462 mm postoperatively) were improved postoperatively. Only in two patients treated with injections of collagen incontinence was cured. The present clinical results demonstrate that, in contrast to injections of collagen, urinary incontinence can be treated effectively with ultrasonography-guided injections of autologous myo- and fibroblasts.     

The effect of mode of delivery on pelvic floor functional anatomy

The objective of this study is to investigate and compare the effects of different modes of delivery on urethral sphincter volume, bladder neck mobility, and changes to levator hiatus distensibility using ultrasound imaging. This study is a prospective observational cohort study. The setting of this study is at a London teaching hospital. The population is composed of 156 women recruited in their first ongoing pregnancy. Primigravid women were recruited between 32 weeks and term. Antenatal ultrasound measurements of levator hiatus and bladder neck mobility were assessed at rest, maximum strain, and maximum valsalva using transvaginal ultrasound imaging. Urethral sphincter volume was calculated using a three-dimensional transvaginal probe. The investigations were repeated at 6 weeks and at 6 months postpartum. Total urethral sphincter volume, rhabdosphincter volume, bladder neck position at rest, and rotational mobility from maximum contraction to maximum valsalva were measured in this study. Levator hiatus area at rest and levator hiatus on valsalva and squeeze were also measured. The 156 women underwent antenatal ultrasound pelvic floor assessment. One hundred ten (71%) completed the 6-month follow-up. There were no differences in the urethral sphincter volume between the different modes of delivery. Overall, the urethral sphincter was smaller after delivery compared to the third trimester. Vaginal delivery was associated with a significantly larger levator hiatus area on valsalva antenatally and at rest, squeeze, and valsalva postnatally compared to caesarean section. Antenatal and postpartum bladder neck mobility was also significantly greater in the women who delivered vaginally. Urethral sphincter changes postpartum are independent of mode of delivery. Vaginal delivery is strongly associated with a larger, more distensible levator hiatus and a greater degree of bladder neck mobility both antenatally and postpartum.     

Histotopography of the female cavernous nerve: a study using donated fetuses and adult cadavers

The purpose of this study was to identify the histotopography of the female cavernous nerve. The study used semi-serial horizontal sections of seven fetuses and ten adult cadavers. In fetuses, the female cavernous nerve ran anteriorly between the distal vagina and the levator ani and entered the corpus cavernosum clitoridis. Its course through the argental hiatus was similar to that of the male cavernous nerve. However, the fascial arrangement along the female cavernous nerve was different from that of the three male fetuses included in this study. In female adults, the putative cavernous nerve was found running along the lateral aspect of the rhabdosphincter, along the superior surface of the urethrovaginal sphincter and around the lateral end of the latter sphincter. Because the female cavernous nerve and lateral vaginal wall are closely related, surgical treatment along the mid- and distal urethra should be conducted cautiously so as not to injure the perivaginal autonomic nerves.     

Adult stem cell therapy of female stress urinary incontinence

OBJECTIVES: To investigate the efficacy of transurethral ultrasound (TUUS)-guided injections of autologous myoblasts and fibroblasts in women with incontinence. METHODS: Between January and June 2005, 20 female patients suffering from stress urinary incontinence (SUI) were included. Skeletal muscle biopsies were taken from the left arm to obtain cultures from autologous fibroblasts and myoblasts. By TUUS guidance the fibroblasts were injected into the urethral submucosa and the myoblasts were injected into the rhabdosphincter. A defined incontinence score, quality-of-life score and urodynamic, electromyographic, and laboratory parameters, as well as morphology and function of urethra and rhabdosphincter were evaluated before and up to 2 yr after therapy. RESULTS: Eighteen of 20 patients were cured 1 yr after injection of autologous stem cells and in 2 patients SUI was improved. Two years after therapy 16 of the 18 patients presented as cured, 2 others were improved, and 2 were lost to follow-up. Incontinence and quality-of-life scores were significantly improved postoperatively. The thickness of urethra and rhabdosphincter as well as activity and contractility of the rhabdosphincter were also statistically significantly increased after therapy. CONCLUSIONS: Clinical results demonstrate that SUI can be treated effectively with autologous stem cells. The present data support the conclusion that this therapeutic concept represents an elegant and minimally invasive treatment modality to treat SUI.     

Origins and courses of the nervous branches to the male urethral sphincter

The striated sphincter of the male urethra, the so-called rhabdosphincter, contributes significantly to urethral closure pressure. It is generally agreed that the somatic nerve fibers from the pudendal nerve innervate the rhabdosphincter, and the autonomic nerve fibers innervate the smooth muscle of the urethra. Although it is difficult to clearly identify the rhabdosphincter macroscopically, we minutely investigated the nerve branches to the urethral sphincter muscle region in 10 male pelvic halves. In addition, the origins and courses of the pudendal plexus in 88 male pelvic halves were investigated. To this region were given branches of the pudendal nerve and the pelvic plexus. The branches from the pelvic plexus to the region generally originated from S4 as the lowest branch of the pelvic splanchnic nerve, and ran along the rectal attachment of the levator ani. The caudal root of the pelvic splanchnic nerve formed a common trunk with the nerve to the levator ani (94%). Various connections were sometimes observed between the pudendal nerve and the branches medial to the levator ani. It is suggested that the somatic nerve fibers from the nerve to the levator ani or from the pudendal nerve might also join the nerve branches to the region from the pelvic plexus.

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Origine et trajet des branches nerveuses destinées au sphincter uréthral de l'homme

Résumé Le sphincter strié de l'urètre de l'homme, aussi appelé rhabdosphincter, contribue significativement a la pression de clôture de l'urètre. Il est généralement admis que les fibres somatiques du nerf pudendal innervent le sphincter strié, et que les fibres nerveuses autonomes innervent le muscle lisse de l'urètre. Ben qu'il soit difficile d'identifier macroscopiquement le sphincter strié, nous avons observé microscopiquement les branches nerveuses destinées aux muscle sphincter urétral sur dix hémi-pelvis masculins. De plus, l'origine et le trajet du plexus pudendal ont été explorés sur 88 hémi-pelvis masculins. Cette région recevait des branches du nerf pudendal et du plexus pelvien. Les branches du plexus pelvien pour cette zone provenaient en général de S4, sous la forme de la branche la plus distale du nerf splanchnique pelvien, et cheminaient le long de l'insertion rectale du muscle élévateur de l'anus. La racine caudale du nerf splanchnique pelvien formait un tronc commun avec le nerf du muscle élévateur de l'anus (94%). Des connexions variables ont parfois été observées entre le nerf pudendal et les branches médiales au muscle élévateur de l'anus. Ceci suggère que les fibres nerveuses somatiques du nerf du muscle élévateur de l'anus ou du nerf pudendal puissent rejoindre les branches nerveuses provenant du plexus pelvien.

     

The male rectourethralis and deep transverse perineal muscles and their relationship to adjacent structures examined with successive slices of celloidin-embedded pelvic viscera

Background

The precise relationship of the structures dorsal to the membranous urethra, including the rectourethralis muscle, the rhabdosphincter, the deep transverse perineal muscle (DTPM), the perineal body, and Denonvillier's fascia, remains controversial.

Objective

Our aim was to reexamine the detailed anatomy of the rectourethralis muscle and the deep transverse perineal muscle and their relationship with adjacent structures.

Design, setting, and participants

The pelvic viscera, including bladder, prostate, and rectum, were obtained from 20 formalin-fixed adult male cadavers.

Measurements

The pelvic viscera were embedded in celloidin and then cut into successive slices with an immersing-alcohol microtome. All slices were explored with anatomic microscopy.

Results and limitations

The longitudinal muscle of the anterior rectal wall was divided into anterior and posterior bundles at the junction of the rectum and anal canal. The intermediate fibers of the anterior bundle ended at the perineal body. The lateral fibers of the anterior bundle terminated at the posterior connective tissue of the bulbus penis. The DTPM occupied the space between the rhabdosphincter, rectum, and the bilateral levator ani muscle. Denonvillier's fascia terminated at the junction of the prostate and rhabdosphincter. Numerous slender nerves coming from the neurovascular bundle perforated the DTPM.

Conclusions

The anterior bundle of the longitudinal muscle of the rectum inserts into the bulbus penis forming the rectourethralis muscle and ends at the perineal body forming the rectoperinealis muscle. The anterior bundle and DTPM together may contribute to the rectal angle of the anterior rectal wall, and they support the posterior border of the rhabdosphincter.     

Pharmacologic treatment in postprostatectomy stress urinary incontinence

OBJECTIVES: The aim of this study was to assess efficacy and safety of association of duloxetine and rehabilitation compared with rehabilitation alone in men with SUI after radical retropubic prostatectomy (RRP), and to compare continence rate even after planned duloxetine suspension. METHODS: After catheter removal, 112 patients were randomized to receive rehabilitation and duloxetine (group A) or rehabilitation alone (group B), for 16 wk. Inclusion criteria: postprostatectomy SUI with daily incontinent episodes frequency (IEF) of four or greater. After 16 wk both groups suspended duloxetine/placebo and continued rehabilitation. All patients completed incontinence quality of life (I-QoL) questionnaire and bladder diary. Wilcoxon test was used to analyse changes in IEF and in I-QoL score; Fisher exact test was used to compare continent patients between the groups. RESULTS: Adverse events for duloxetine was 15.2%. 102 men completed the study. There was a significant decrease in pad use in group A. After 16 wk, 39 patients versus 27 were dry (p=0.007). At 20 wk, 4 wk after planned interruption of duloxetine, we observed a U-turn, 23 patients were completely dry in group A versus 38 in group B (p=0.008). Whereas, after 24 wk, 31 in group A versus 41 in group B were dry (p=0.08). The decrease in IEF and improvements in I-QoL scores were significantly greater in group A for the first 16 wk. CONCLUSIONS: The data suggest that combination therapy might provide another treatment option for SUI in men that might increase the percentage of early postsurgery continence.     

Posterior Musculofascial Reconstruction After Radical Prostatectomy: A Systematic Review of the Literature

Context

In 2001, Rocco et al. described a surgical technique whose aim was the reconstruction of the posterior musculofascial plate after radical prostatectomy (RP) to improve early return to urinary continence. Since then, many surgeons have applied this technique—either as it was described or with some modification—to open, laparoscopic, and robot-assisted RP.

Objective

To review the outcomes reported in comparative studies analysing the influence of reconstruction of the posterior aspect of the rhabdosphincter after RP. The main outcome evaluated was urinary continence at 3–7 d, 30–45 d, 90 d, 180 d, and 1 yr after catheter removal.

Evidence acquisition

A systematic review of the literature was performed in November 2011, searching the Medline, Embase, Scopus, and Web of Science databases. A “free-text” protocol using the terms posterior reconstruction of the rhabdosphincter, posterior rhabdosphincter, and early continence was applied. Studies published only as abstracts and reports from meetings were not included in this review. One thousand seven records were retrieved from the Medline database, 1541 from the Embase database, 1357 from the Scopus database, and 1041 from the Web of Science database. The authors reviewed the records to identify studies comparing cohorts of patients who underwent RP with or without restoration of the posterior aspect of the rhabdosphincter. Only papers evaluating use of this technique as the only technical modification among the groups were included. A cumulative analysis was conducted using Review Manager v.5.1 software (Cochrane Collaboration, Oxford, UK).

Evidence synthesis

Eleven studies were identified in the literature search, including two randomised controlled trials (RCTs), which were negative studies. The cumulative analysis of comparative studies showed that reconstruction of the posterior musculofascial plate improves early return of continence within the first 30 d after RP (p = 0.004), while continence rates 90 d after surgery are not affected by use of the reconstruction technique. The statistical significance of the reconstruction seems to decrease when higher continence rates are reported. Use of posterior rhabdosphincter reconstruction does not seem to be related to positive surgical margin (PSM) rates or with complications like acute urinary retention (AUR) and bladder neck stricture (BNS). Some studies suggested lower anastomotic leakage rates with the posterior musculofascial plate reconstruction technique.

Conclusions

The role of reconstruction of the posterior musculofascial plate in terms of earlier continence recovery is encouraging but still controversial. Methodological flaws and poor surgical standardisation seem to be the major causes. In two RCTs and one parallel (not randomised) group trial, posterior rhabdosphincter reconstruction offered no significant advantage for return of early continence after RP. No significant complications related to the posterior musculofascial plate reconstruction technique have been reported so far. A multicentre RCT is necessary to clarify the possible role of the technique in terms of earlier continence recovery.     

Female perineal membrane: a study using pelvic floor semiserial sections from elderly nulliparous and multiparous women

To describe the architecture and topohistology of the female perineal structures, especially the perineal membrane (PM), we examined frontal sections (one side) and horizontal or transverse sections (another side) of 15 bisectioned pelvic floors. The PM, notably comprising elastic fibers, extended mediolaterally or transversely on the immediately inferior side of the rhabdosphincter area. More posteriorly, the elastic fibers more tilted along the long axis of the vagina and became lining the lateral vaginal wall as a fibrous skeleton. The compressor urethrae and urethrovaginal sphincter were embedded in and interdigitated with the PM. The elastic fiber architecture of the PM was similar to the rectovaginal septum. We hypothesize that the PM plays a role of a shock-absorber at the interface between the levator ani and distalmost vagina. A standard diagram of the female perineal structures is necessary to be revised.     

Three-dimensional transrectal ultrasound of the male urethral rhabdosphincter

The rhabdosphincter of the male urethra is an omega-shaped loop of striated muscle fibers that surrounds the membranous urethra at its lateral and anterior aspects. We investigated whether this muscle can be visualized by means of three-dimensional ultrasound to define morphological and dynamic ultrasound criteria. We examined the rhabdosphincter of the male urethra in 77 patients by means of this new imaging technique; 37 patients presented with urinary stress incontinence after transurethral resection of the prostate or radical prostatectomy while 40 were fully continent after radical prostatectomy and served as a control group. Contractility of the muscle was quantified by a specially defined parameter (rhabdosphincter–urethra distance). The anatomical arrangement and the contractions of the rhabdosphincter-loop could be clearly visualized in three-dimensional transrectal and transurethral ultrasound; during contraction the rhabdosphincter retracts the urethra, pulling it towards the rectum. We detected defects and postoperative scarrings in the majority of the patients with postoperative urinary stress incontinence. Furthermore, the patients presented with thinnings in parts of the muscle and atrophies of the rhabdosphincter. The rhabdosphincter–urethra distance was significantly lower in the incontinent group than in the continent group (59 vs. 1.42 mm). Our study shows that the rhabdosphincter of the male urethra can be visualized by means of three-dimensional transrectal ultrasound. The sonographic pathomorphological findings of postoperative urinary stress incontinence are well correlated well with the clinical symptoms