Stammzelltherapie der Harninkontinenz

Experimental and clinical studies investigated whether urinary incontinence can be effectively treated with transurethral ultrasound-guided injections of autologous myoblasts and fibroblasts.This new therapy was performed in eight female pigs. It could be shown that the injected cells survived well and that new muscle tissue was formed. Next, 42 patients (29 women, 13 men) suffering from urinary stress incontinence were treated. The fibroblasts were mixed with a small amount of collagen as carrier material and injected into the urethral submucosa to treat atrophies of the mucosa. The myoblasts were directly injected into the rhabdosphincter to reconstruct the muscle and to heal morphological and functional defects. In 35 patients urinary incontinence could be completely cured. In seven patients who had undergone multiple surgical procedures and radiotherapy urinary incontinence improved. No side effects or complications were encountered postoperatively.The experimental as well as the clinical data clearly demonstrate that urinary incontinence can be treated effectively with autologous stem cells. The present data support the conclusion that this new therapeutic concept may represent a very promising treatment modality in the future.     

Autologous myoblasts and fibroblasts for female stress incontinence: a 1-year follow-up in 123 patients

OBJECTIVE: To assess the efficacy and safety of the application of autologous myoblasts and fibroblasts for treating female stress urinary incontinence (SUI) after a follow-up of >/=1 year. PATIENTS AND METHODS: In all, 123 women with SUI (aged 36-84 years) were treated with transurethral ultrasonography-guided injections with autologous myoblasts and fibroblasts obtained from skeletal muscle biopsies. The fibroblasts were suspended in a small amount of collagen as carrier material and injected into the urethral submucosa, while the myoblasts were implanted into the rhabdosphincter. All patients were evaluated before and 12 months after the injection using the Incontinence and Quality of Life Instrument (I-QOL) scores, urodynamic variables, and morphology and function of the urethra and rhabdosphincter. RESULTS: At 1 year after implanting the cells, 94 of the 119 women (79%) were completely continent, 16 (13%) had a substantial improvement and nine (8%) a slight improvement. Four patients were lost to follow-up.The incontinence and I-QOL scores, and the thickness, contractility and electromyographic activity of the rhabdosphincter were significantly improved after treatment. CONCLUSIONS: These results show the efficacy and safety of transferring autologous myoblasts and fibroblasts in the treatment of female SUI, after a follow-up of 1 year.     

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.     

Transurethral collagen injection for treatment of stress urinary incontinence

Summary Minimally invasive treatment of urinary incontinence has become a subject of major interest in recent years. We examined the use of transurethral collagen injection for incontinence treatment. A total of 48 patients were selectet for this procedure from April 1993 to February 1997 – 26 male patients (19 post-RPX incontinence and 7 post-TUR incontinence) and 22 female patients (all after previous incontinence surgery) were treated by injection of collagen into the continence region. The whole group underwent an average of 1.8 sessions, and a mean collagen injection volume of 14.5 ml was delivered per session. Mean follow-up was 9.2 months. Of the female population, 68.2 % were cured or greatly improved. In the male population only 47.3 % of the post-RPX patients and 6/7 of the post-TUR patients benefited from the procedure. In males, treatment outcome depends on the degree of pretreatment incontinence, because all grade III incontinence patients did worse. Therefore we conclude: transurethral collagen injection is an interesting method in the treatment of urinary incontinence if proper patient selection is assured.      

Collagen injection in the management of post-radical prostatectomy intrinsic sphincteric deficiency.

Transurethral injection of collagen is a minimally invasive option for the treatment of urinary incontinence secondary to intrinsic sphincteric deficiency (ISD). We report on the results of transurethral injection in 21 men with urinary incontinence secondary to ISD. Twenty-one consecutive men with a mean age of 69.5 years (range, 51-84), with ISD documented by demonstrating urinary leakage with Valsalva maneuver on physical examination and by video-urodynamic studies were treated with transurethral collagen injection. The etiologies of the incontinence were radical retropubic prostatectomy (RRP) in seven (33.3%), RRP followed by external radiation therapy in seven (33.3%), and transurethral resection of the prostate (TURP) with subsequent RRP in seven (33. 3%). The mean total volume of collagen injected per patient was 18.4 mL (range, 1-44.5). The average number of injections was 2.9 (range, 1-5). The mean follow-up was 12.5 months (range, 1-39). One (5%) patient became dry, 12 (57%) had significant improvement, and eight (38%) had no change. Overall pad use decreased from 2.5 pads/day to 1.68 pads/day, before and after collagen injection (P = 0.014). No difference in outcomes was demonstrated in African American men versus Caucasian American men (P = 0.38), age (<65 and >65 years, P = 0.88), presence of erectile dysfunction, or duration of incontinence (<20 or >20 months, P = 0.71). There were no reported complications. Collagen injection has minimal morbidity and is a viable option for improving incontinence status in men. Neither age, race, erectile function, nor duration of incontinence appears to affect treatment outcome. Neurourol. Urodynam. 18:653-658, 1999.     

Collagen injection for the treatment of incontinence after cystectomy and orthotopic neobladder reconstruction in women

PURPOSE: We determine the clinical efficacy of endoscopically injected collagen for the treatment of new onset urinary incontinence in women following cystectomy and orthotopic neobladder. MATERIALS AND METHODS: Three women 58 to 74 years old underwent transurethral collagen injection for stress urinary incontinence following cystectomy and orthotopic neobladder. Before cystectomy 2 women denied having any stress urinary incontinence while 1 complained of mild incontinence. Onset of incontinence following cystectomy and neobladder formation ranged from 8 months to 3 years, and average pad use ranged from 3 to 5 per 24-hour period. All patients underwent video urodynamic evaluation before collagen injection. Neobladder capacity was 180 to 400 cc and Valsalva leak point pressures ranged from 30 to 60 cm. water. RESULTS: A total of 6 injections were given, including 3 injections in 1 patient, 2 in 1 and 1 in 1. All 3 women had significant improvement or became dry with initial injection but required repeat injections to maintain improved continence status. At 7 to 8 months after the last injection 1 woman was dry, 1 used 1 or no pad daily and 1 reported no durable change in stress urinary incontinence. CONCLUSIONS: Collagen injection appears to be a successful, minimally invasive treatment for new onset stress urinary incontinence following cystectomy and orthotopic neobladder in women.     

亲水性聚丙烯酰胺凝胶腔内注射治疗女性压力性尿失禁

目的 评估亲水性聚丙烯酰胺凝胶(生物凝胶)经尿道腔内注射治疗女性压力性尿失禁的疗效。方法 24例女性压力性尿失禁患膀胱镜直视下于后尿道近膀胱开口0．5-lcm的3,6，9点处黏膜下穿刺注射生物凝胶平均12．2(6．20)ml／次。结果 腔内注射一次18例，二次5例，三次1例，累积平均注射量18．9(6—38)ml。术后尿道平均延长1．03cm，膀胱颈部尿道121周径平均缩小3．1lcm，症状消失13例，占54．2％；改善11例，占48．5％；无并发症和不良反应发生。结论 生物凝胶腔内注射治疗女性压力性尿失禁疗效确切，创伤微小，可重复注射，可选择为压力性尿失禁的外科治疗方法。     

Long-term results after antegrade collagen injection for stress urinary incontinence following radical retropubic prostatectomy

OBJECTIVE: To evaluate the long-term success of antegrade collagen injection in men with stress urinary incontinence after radical prostatectomy. METHODS: Between October 1994 and January 1996, 20 patients underwent antegrade collagen injection for stress urinary incontinence caused by radical prostatectomy. Evaluation by pad test, urodynamics, and subjective scores was performed before and after injection. RESULTS: At a mean follow-up of 28 months, 10% of the patients were cured and 35% were improved. All patients received a single treatment (mean total volume of collagen injected 14.5 mL). In 11 patients without long-term improvement, 2 had undergone irradiation previously and 7 had failed retrograde collagen injections. Two patients with vesical neck contracture were successfully treated. Preoperative incontinence severity and stress leak point pressure did not correlate with failure. CONCLUSIONS: A 45% cured or improved rate at long-term follow-up is possible in men with stress incontinence after radical prostatectomy using a single antegrade collagen injection. Although antegrade delivery of collagen for stress incontinence minimized short-term, technique-related failures, for a substantial number of patients therapy had failed at long-term follow-up.     

Endoscopic teflon injection in the treatment of female stress urinary incontinence

Fifty six women with urinary stress incontinence were treated with transurethral teflon injections. Forty eight (86 per cent) were completely cured, or showed considerable improvement. No abscesses or other complications were noted, and hospitalization was reduced to two or three days. The procedure is easy to perform and does not preclude subsequent surgery, if required. It is particularly suitable for obese or debilitated patients, or patients who have previously undergone surgery without success.     

Outcome results of transurethral collagen injection for female stress incontinence: assessment by urinary incontinence score

PURPOSE: We assessed the results of collagen injection for female sphincteric incontinence using strict subjective and objective criteria. MATERIALS AND METHODS: We evaluated 63 consecutive women with sphincteric incontinence who underwent a total of 131 transurethral collagen injections. Sphincteric incontinence was confirmed by urodynamics. All patients were treated with 1 to 5 transurethral collagen injections and treatment outcome was classified according to a new outcome score. Cure was defined as no urinary loss due to urge or stress incontinence documented by a 24-hour diary and pad test, and patient assessment that cure was achieved. Failure was defined as poor objective results and patient assessment that treatment failed. Cases that did not fulfill these cure and failure criteria were considered improved and further classified as a good, fair or poor response. RESULTS: Mean patient age plus or minus standard deviation was 67.7 +/- 12.8 years. All women had a long history of severe stress urinary incontinence, 18 (29%) underwent previous anti-incontinence surgery, and 41% had combined stress and urge incontinence. Preoperatively diary and pad tests revealed a mean of 7.5 +/- 4.6 incontinence episodes and 152 +/- 172 gm. of urine lost per 24 hours. Overall 1 to 5 injections were given in 26, 17, 13, 3 and 4 patients, respectively. Mean interval between injections was 4.4 +/- 5.7 months, mean followup was 12 +/- 9.6 months, and mean interval between the final injection and outcome assessment was 6.4 +/- 4.9 months. There was a statistically significant decrease in the total number of incontinence episodes per 24-hour voiding diary after each injection session. Although there was a clear trend toward decreased urinary loss per 24-hour pad test, statistical significance was not established. Using the strict criteria of our outcome score overall 13% of procedures were classified as cure, 10%, 17% and 42% as good, fair and poor, respectively, and 18% as failure. CONCLUSIONS: As defined by strict subjective and objective criteria, we noted a low short-term cure rate after collagen injection in women with severe sphincteric incontinence. It remains to be determined how patients with less severe incontinence would fare using our outcome assessment instruments.     

Comparison of bone-anchored male sling and collagen implant for the treatment of male incontinence

AIM: To compare the effectiveness of transurethral collagen injection and perineal bone-anchored male sling for the treatment of male stress urinary incontinence (SUI). METHODS: Seventy-one men with SUI underwent either transurethral collagen injections (n = 34) or perineal bone-anchored male sling (n = 37) between June 1999 and October 2003. Most of the patients in each group had radical retropubic prostatectomy and/or external beam radiation therapy (EBRT) in relation to the cause of incontinence. There was one patient in both groups who only had EBRT for the cause. The mean duration of incontinence were 4.2 and 4.4 years, respectively. Collagen injections were carried out transurethrally either under regional or general anesthesia until co-aptation of mucosa was observed. The male sling was placed under spinal anesthesia with a bone drill using either absorbable or synthetic materials. Retrospectively, all patients were assessed for continence status and procedure-related morbidity, if present. The outcome of both procedures was also compared with the degree of incontinence. RESULTS: Ten (30%) patients in the collagen group showed either significant improvement or were cured following injections. Preoperatively, the mean pad use in collagen group was 4.5 (SD 2.8) per day, whereas it was 2.2 (SD 1.1) after the injection(s). Collagen injection failed in 24 (70%) of the patients. Patients who received the male sling had a mean preoperative pad use of 3.7 (SD 1.5) and postoperatively, the number decreased to 1.6 (SD 1.2). Most of the patients in this group were either totally dry or significantly improved (n: 28, 76%). There was a statistically significant difference between two groups in respect to success rate (P < 0.05). Analysis of treatment outcome with the degree of incontinence revealed that the male sling is most effective in patients with minimal-to-moderate incontinence. CONCLUSIONS: Our results suggest that the male sling, a minimally invasive procedure, is more effective than collagen implant in the treatment of mild-to-moderate SUI in men.     

Functional and histological changes after myoblast injections in the porcine rhabdosphincter

OBJECTIVE: Transurethral ultrasound-guided injection of autologous myoblasts has recently been shown to cure urinary stress incontinence. In the present study, the dose-dependent changes in maximal urethral closure pressures after application of myoblasts were investigated in a porcine animal model. METHODS: Myoblast cultures were grown from a porcine muscle biopsy. The biopsy was enzymatically dissociated by using a modified cell dispersion technique. Single myoblasts in suspension were manually collected with a micropipette under microscopic control. Next a clonal myoblast culture was prepared. Before the cells were applied, fluorescence labelling (PKH) was used to assess integration of the injected myoblasts into the rhabdosphincter. With the help of a transurethral ultrasound probe (23 F, 11 MHz) and a special injection system, the myoblasts were injected into the rhabdosphincter of five pigs under direct sonographic control. Into two different areas of the rhabdosphincter, increasing different cell counts were injected (total volume 1.5 ml). At each area, 10 depots of 150 microl volume were injected all along the rhabdosphincter. The following cell counts were used: 1.5 x 10(6), 2.1 x 10(6), 4.2 x 10(6) (low range) 5.69 x 10(6), 8.1 x 10(6), 1.13 x 10(7), 1.6 x 10(7) (mid range) 2.26 x 10(7), 4.4 x 10(7), and 7.8 x 10(7) (high range). To avoid possible cell rejection, we immunosuppressed the pigs with daily cortisone (1g Solu Dacortin) because allogenic myoblasts were used. Urethral pressure profiles (UPPs) were measured before and 3 wk postoperatively before the pigs were put to sleep. The lower urinary tract was removed in all pigs for histological analysis. RESULTS: Histological examination of the specimens revealed that the injected cells had survived at the injection site and had formed new myofibres. Overall the UPP curves revealed dose-dependent changes. Statistically significant increased pressure values of up to more than 300% could be observed in all cases in which higher concentrations of cells had been applied. Increases were also noted in mid range concentrations although not to such a high extent (approximately 150%). Pressure values had even diminished (approximately 50%) after injecting the three lowest concentrations (1.5 x 10(6), 2.1 x 10(6), 4.2 x 10(6)). CONCLUSIONS: The present results show that the effects after application of myoblasts into the rhabdosphincter are dose-dependent.     

Correlation of urodynamic results and urethral coaptation with success after transurethral collagen injection

Objectives

We correlated preoperative urodynamic and intraoperative endoscopic findings with initial improvement, single collagen injection effectiveness for intrinsic sphincter deficiency (ISD), and long-term improvement following transurethral collagen injection for stress urinary incontinence (SUI).

Methods

Since 1993, 79 patients have been treated with transurethral collagen injection by the same urologist. Of these patients, intraoperative photographs of urothelial coaptation immediately after injection were available in 67 patients: 35 women with ISD, 24 men with incontinence, primarily following prostatectomy, and 8 children with neurogenic bladder. Urothelial coaptation was described as snug,fair, or poor. Preoperative Valsalva leak point pressure (VLPP), detrusor instability, impaired bladder compliance, bladder neck appearance, urothelial scarring, and degree of coaptation were correlated with both initial and long-term improvement. Initial improvement was compared with long-term improvement.

Results

Initial improvement was experienced by 85% of all the subjects (86% of the women, 80% of the men, and 100% of the children with a neurogenic bladder condition). Overall, 31% of patients had long-term improvement after a mean follow-up of 2.2 years, including 43% of the women, 13% of the men, and 33% of the children. The patients underwent a mean of 1.5 (1 to 4) collagen injections. There was a significant correlation between degree of coaptation and initial improvement (P = 0.003), but not with long-term improvement. There was no correlation between VLPP, detrusor instability, impaired compliance, bladder neck appearance, or urethral scarring and initial improvement. There was no correlation between any parameter and long-term improvement or between initial and long-term improvement.

Conclusions

Initial endoscopic appearance following collagen injection predicted initial, but not long-term, improvement after one collagen injection. Initial improvement was high in both men and women but decreased considerably over time, more so in men, and was not significantly correlated with long-term success. Urodynamic and endoscopic findings do not predict long-term success following collagen injection.     

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     

Complications of sterile abscess formation and pulmonary embolism following periurethral bulking agents

PURPOSE: Agents currently used in the treatment of urinary incontinence secondary to intrinsic sphincter deficiency are effective and minimally invasive. Ensuring a lack of sensitivity to the product or use of autologous material, such as fat, minimizes significant problems. However, local and systemic complications can occur with any bulking agent. We describe rare complications of periurethral bulk injections. MATERIALS AND METHODS: Three cases of sterile abscess formation and 1 of pulmonary embolism after periurethral bulk injections were reviewed. Two patients with intrinsic sphincter deficiency were treated with transurethral injection of glutaraldehyde cross-linked collagen at the Mayo Clinic, 1 also treated with collagen for intrinsic sphincter deficiency was referred from elsewhere and 1 underwent periurethral injection of autologous fat for intrinsic sphincter deficiency elsewhere. Clinical information and patient followup were obtained from medical records and discussion with treating physicians. RESULTS: Three patients treated with collagen presented with sterile abscesses at the injection site after routine transurethral injection. Documentation of the abscesses included cystoscopic findings, magnetic resonance imaging of the pelvis and/or transvaginal ultrasound. Drainage procedures for relief of obstructive and irritative voiding symptoms were required in 2 patients. In 1 of these patients transurethral unroofing failed, and transvaginal incision and drainage were required while the other had slow spontaneous improvement but a mass remained at the injection site 3 months later. Repeat skin testing was negative in 2 of 3 cases. Currently, these 3 patients are asymptomatic except for continued urinary incontinence. Pulmonary embolism was documented in 1 patient who underwent periurethral autologous fat injection. This patient survived without long-term consequences but was maintained on ventilatory support for a short time. CONCLUSIONS: In general, periurethral injection of bulk agents is safe and effective. However, injectable bulk agents are not without risk of complications, some of which are life threatening and others of considerable morbidity that may require operative intervention.     

Periurethral autologous fat injection as treatment for female stress urinary incontinence: a randomized double-blind controlled trial

PURPOSE: We evaluated the effectiveness of periurethral autologous fat injection as treatment for female stress urinary incontinence. MATERIALS AND METHODS: Women with stress incontinence were randomized in a double-blind fashion to receive periurethral injections of autologous fat (treatment group) or saline (placebo group). After injection patients were evaluated monthly for 3 months by a validated standardized incontinence questionnaire, 1-hour pad test and cough test. Patients who remained incontinent were offered repeat injection using the same initial agent to a maximum of 3 injections. Every 3 months after injection patients were assessed by a standardized questionnaire, pad test, cough test and urodynamics. Those who did not qualify for repeat injection at 3 months were then followed 6, 9, 12, 18 and 24 months or until failure. RESULTS: Of the 68 women enrolled 35 received fat and 33 received saline injections. The groups were comparable in terms of baseline parameters. A total of 56 patients completed the study, including 27 in the fat and 29 in the placebo group, for a total of 189 injections (91 fat and 98 saline). At 3 months 6 of 27 (22.2%) and 6 of 29 (20.7%) women were cured or improved in the fat and saline groups, respectively. Complications included cystitis in 9 of 189 injections, urinary retention in 6 in the fat injection group, urge incontinence in 9 of 68 patients and pulmonary fat embolism resulting in death in 1 of 189 procedures. CONCLUSIONS: In this study periurethral fat injection did not appear to be more efficacious than placebo for treating stress incontinence.     

Periurethral collagen injection: a long-term follow-up study

OBJECTIVE: To determine the long-term success of the periurethral injection of collagen (Contigen(R), Bard UK) in women with genuine stress incontinence. PATIENTS AND METHODS: Sixty-one women with genuine stress incontinence were enrolled in a trial of periurethral collagen injections between 1 September 1990 and 31 August 1992. They were assessed at 1, 3, 6, 12 and 24 months after the last collagen injection. In 1998, their notes were reviewed, and a standardized questionnaire was sent to 46 women who were still alive and had undergone no further anti-incontinence surgery. RESULTS: Of the 53 women who were either known failures or who had follow-up information beyond 5 years, 26% were subjectively improved. Women who had a maximum urethral closure pressure of >20 cmH2O and those who had urinary incontinence for <10 years before their first injection were more likely to have had long-term success. There was no correlation between long-term success and the number of previous operations, body mass index, age or preoperative pad loss. Neither the number of injection sessions, total volume of collagen injected nor perceived bulking at the time of surgery affected long-term success rates. Of the 14 women who considered themselves subjectively improved, seven had daily incontinence and only one was completely dry. Urinary retention and urinary tract infection were the most common complications. In addition, one woman reported a flare-up of her skin test and transient 'flu-like symptoms 2 weeks after the injection, and one woman developed a right upper lobe pneumonia 2 weeks after the collagen injection. CONCLUSION: The long-term results of periurethral collagen injections are disappointing. We found no evidence to support the use of periurethral collagen injections in women with intrinsic sphincter deficiency, who had a higher failure rate than those with hypermobility. Further research is essential to develop agents that are not immunogenic, produce minimal inflammatory response and yet are durable.     

Células madre derivadas de músculo para la incontinencia urinaria de esfuerzo

The knowledge of the urinary effort incontinence (UEI) has increased, giving like result an ample range of different therapeutic options available. The middle urethra and external urethral sphincter are the focus in management of UEI. Stem cells therapy for the regenerative repair of the deficient sphincter has been the leading research of incontinence. Obtaining autologous myoblasts and fibroblasts of skeletal muscle-biopsies, cultivating them and transplanting them after its differentiation, into the external urethral sphincter it warns a new concept in the treatment of the incontinence. Instead of using heterologous materials such as synthetic mesh (slings) or bulking agents (collagen, silicone, etc); we now have the potential to restore function with the use of autologous stem cells.     

Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: Report of two initial cases

Objectives:   To report a novel cell therapy using autologous adipose tissue-derived stem cells (ADSC) for stress urinary incontinence caused by urethral sphincteric deficiency and the outcomes in two initial cases undergoing periurethral injection of stem cells for the treatment of urinary incontinence after radical prostatectomy.
Methods:   Two patients with moderate stress incontinence after radical prostatectomy were enrolled. After liposuction of 250 mL of adipose tissue from the abdomen, we isolated ADSC from this tissue by using the Celution system. Subsequently, the isolated ADSC and a mixture of stem cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Short-term outcomes during a 12-week follow-up were assessed by a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography, and magnetic resonance imaging.
Results:   Urinary incontinence progressively improved after 2 weeks of injection up to 12 weeks in terms of decreased leakage volume in a 24-h pad test, decreased frequency and amount of incontinence, and improved quality of life as per the questionnaire. In urethral pressure profile, both maximum urethral closing pressure and functional profile length increased. Ultrasonography and magnetic resonance imaging showed sustained presence of the injected adipose tissue. Enhanced ultrasonography showed a progressive increase in the blood flow to the injected area. No significant adverse events were observed peri- and postoperatively.
Conclusion:   This preliminary study showed that periurethral injection of the autologous ADSC is a safe and feasible treatment modality for stress urinary incontinence.     

New onset vesicovaginal fistula after transurethral collagen injection in women who underwent cystectomy and orthotopic neobladder creation: presentation and definitive treatment

PURPOSE: We present our experience with collagen injection for treating urinary incontinence after cystectomy and orthotopic bladder substitution in women. We discuss the efficacy of collagen injection, specific complications and subsequent definitive therapy. MATERIALS AND METHODS: We performed cystectomy and orthotopic bladder substitution in 2 women for muscle invasive transitional cell carcinoma of the bladder. In each case new onset stress urinary incontinence developed after surgery that was refractory to conservative therapy. Intrinsic sphincter deficiency was diagnosed in each patient by video urodynamic studies. Initial treatment involved transurethral collagen injections but subsequent intervention was required due to resultant complications and primary therapy inefficacy. RESULTS: Collagen (3.5 cc per session) was injected in 1 case at 2 treatment sessions and in the other at 3. Incontinence symptoms did not significantly improve in either patient and a new onset vesicovaginal fistula developed 2 days and 1 month after collagen injection, respectively. Subsequently in each case 1-stage transvaginal primary fistula repair was done in multiple layers with a pubovaginal sling procedure. Six months after repair there has been no recurrent fistula and the women remain hypercontinent, requiring intermittent self-catheterization. They are satisfied with their eventual lower tract function and overall outcome. CONCLUSIONS: Collagen injection for type 3 stress urinary incontinence after cystectomy and orthotopic bladder replacement in women may not be as effective and innocuous as in patients with a native bladder. Initial treatment with a pubovaginal sling procedure should be considered.