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.     

Increased urethral resistance by periurethral injection of low serum cultured adipose‐derived mesenchymal stromal cells in rats

Objectives: To evaluate the effects of a periurethral injection of low serum cultured adipose tissue‐derived mesenchymal stromal cells (LASC) and to develop a new autologous cell therapy for stress urinary incontinence. Methods: F344 rats were divided into three groups as based on the periurethral injection of LASC, GAX collagen or vehicle (control). At 2 and 4 weeks after injection, leak point pressure (LPP) was measured before and after transection of the pelvic nerves. For cell tracking, LASC of green fluorescent protein transgenic rats were injected into nude rats. Results: At 2 weeks, both the LASC and collagen groups showed significantly higher LPP than the control group. At 4 weeks, the increase in LPP in the LASC group remained, whereas LPP in the collagen group decreased to baseline levels. In the absence of the urethral closure reflex after transection of the pelvic nerves, LPP in the LASC group was significantly higher than that in the other two groups. Histologically, the size of the urethral lumen was smaller in the LASC group than the collagen group. At 4 weeks, most of the LASC were positive for myogenic antigens including α‐smooth muscle actin, desmin and calponin I. Conclusions: Periurethral injection of autologous LASC capable of myogenic differentiation made a greater contribution to the increase in urethral resistance than did the conventional collagen bulk injection. Thus, its use for treatment of stress urinary incontinence can be postulated.     

Persistence and survival of autologous muscle derived cells versus bovine collagen as potential treatment of stress urinary incontinence

PURPOSE: We explored the use of autologous muscle derived cells as a method of treating stress urinary incontinence. We determined whether urethral muscle derived cell injection is feasible and compared it with bovine collagen injection. MATERIALS AND METHODS: Muscle derived cells isolated from female Sprague-Dawley rats were first transduced with retrovirus carrying the transgene for beta-galactosidase. We injected approximately 1 to 1.5 x 106 cells into the bladder wall and proximal urethra of 6 autologous animals. Tissue was harvested after 3 and 30 days, sectioned, stained for fast myosin heavy chain and assayed for beta-galactosidase. To compare muscle derived cell and bovine collagen injections 100 microl. of commercially available bovine collagen were also injected in Sprague-Dawley female rats. Tissue was harvested in 3 animals each after 3 and 30 days, sectioned and stained for trichrome. Subsequently, 3 adult SCID mice were used to compare the level of transgene expression at each time point after injecting 1.5 x 106 cells per injection, which were transduced with adenovirus carrying the transgene for beta-galactosidase. RESULTS: A large number of cells expressing beta-galactosidase were observed in the bladder and urethral wall 3 and 30 days after autologous cell injection in Sprague-Dawley rats. The persistence of primary muscle derived cells at 3 days was similar to that of collagen. However, at 30 days there was significant cell persistence while only a minimal amount of injected bovine collagen was detectable. Approximately 88% of the beta-galactosidase expression at day 3 remained at day 30 in SCID mice. CONCLUSIONS: We present 2 new findings important for the emerging field of urological tissue engineering, including the feasibility of injecting autologous skeletal muscle derived cells into the lower urinary tract and the greater persistence of such injected cells versus injected bovine collagen. Therefore, autologous muscle derived cell injection may be an attractive alternative treatment option for stress urinary incontinence.     

Intra‐articular autologous uncultured adipose‐derived stromal cell transplantation inhibited the progression of cartilage degeneration

The role of uncultured adipose‐derived stromal cells for osteoarthritis treatment remains unclear despite sporadic reports supporting their use in clinical settings. This study aimed to evaluate the therapeutic effects of autologous uncultured adipose‐derived stromal cell transplantation in a rabbit osteoarthritis model. Uncultured adipose‐derived stromal cells isolated from rabbits were administered via intra‐articular injection into the knees after osteoarthritis onset. Animals were sacrificed at 8 and 12 weeks after osteoarthritis onset to compare the macroscopic, histological, and immunohistochemical characteristics between the uncultured adipose‐derived stromal cell and control groups. Co‐culture assay was also performed. The chondrocytes isolated from the model were co‐cultured with adipose‐derived stromal cells. The cell viability of chondrocytes and expression of chondrocyte‐specific genes in the co‐culture (uncultured adipose‐derived stromal cell) group were compared with the mono‐culture (control; chondrocytes only) group. In macroscopic and histological analyses, the uncultured adipose‐derived stromal cell group showed less damage to the cartilage surface than the control group at 8 and 12 weeks after osteoarthritis onset. In immunohistochemical and co‐culture assay, the uncultured adipose‐derived stromal cell group showed higher expression of collagen type II and SRY box‐9 and lower expression of matrix metalloproteinase‐13 than the control group. The cell viability of chondrocytes in the uncultured adipose‐derived stromal cell group was higher than that in the control group. Intra‐articular autologous uncultured adipose‐derived stromal cell transplantation inhibited the progression of cartilage degeneration in a rabbit osteoarthritis model by regulating chondrocyte viability and secreting chondrocyte‐protecting cytokines or growth factors, which promote anabolic factors and inhibit catabolic factors. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1376–1386, 2019.     

Autologous bone‐marrow‐derived mesenchymal stem cell transplantation into injured rat urethral sphincter

Objectives: To evaluate the functional and histological recovery by autologous bone‐marrow‐derived mesenchymal stem cell (BMSC) transplantation into injured rat urethral sphincters. Methods: BMSC were harvested from female Sprague–Dawley retired breeder rats for later transplantation. The cells were cultured, and transfected with the green fluorescence protein gene. The urethral sphincters were injured by combined urethrolysis and cardiotoxin injection. One week after injury, the cultured BMSC were injected autologously into the periurethral tissues. Controls included sham‐operated rats and injured rats injected with cell‐free medium (CFM). Abdominal leak point pressures (LPP) were measured before and after surgery during the following 13 weeks. The urethras were then retrieved for histological evaluation. The presence of green‐fluorescence‐protein‐labeled cells and the regeneration of skeletal muscles, smooth muscles, and peripheral nerves were evaluated by immunohistochemical staining. Results: LPP was significantly reduced in the injured rats. It increased gradually after transplantation, but there was no significant difference between the BMSC and CFM groups. In the BMSC group, transplanted cells survived and differentiated into striated muscle cells and peripheral nerve cells. The proportions of skeletal muscle cells and peripheral nerves in the urethra were significantly greater in the BMSC group compared to the CFM group. Conclusions: Despite a clear trend towards recovery of LPP in BMSC‐transplanted urethras, no significant effect was detected. Further study is required for clinical applications for the treatment of stress urinary incontinence.     

State of the art of where we are at using stem cells for stress urinary incontinence

AIMS: This review aims to discuss: 1) the neurophysiology, highlighting the importance of the middle urethra, and treatment of stress urinary incontinence (SUI); 2) current injectable cell sources for minimally-invasive treatment; and 3) the potential of muscle-derived stem cells (MDSCs) for the delivery of neurotrophic factors. METHODS: A PUB-MED search was conducted using combinations of heading terms: urinary incontinence, urethral sphincter, stem cells, muscle, adipose, neurotrophins. In addition, we will update the recent work from our laboratory. RESULTS: In anatomical and functional studies of human and animal urethra, the middle urethra containing rhabdosphincter, is critical for maintaining continence. Cell-based therapies are most often associated with the use of autologous multipotent stem cells, such as the bone marrow stromal cells. However, harvesting bone marrow stromal stem cells is difficult, painful, and may yield low numbers of stem cells upon processing. In contrast, alternative autologous adult stem cells such as MDSCs and adipose-derived stem cells can be easily obtained in large quantities and with minimal discomfort. Not all cellular therapies are the same, as demonstrated by the differences in safety and efficacy from muscle-sourced MDSCs versus myoblasts versus fibroblasts. CONCLUSIONS: Transplanted stem cells may have the ability to undergo self-renewal and multipotent differentiation, leading to sphincter regeneration. In addition, such cells may release, or be engineered to release, neurotrophins with subsequent paracrine recruitment of endogenous host cells to concomitantly promote a regenerative response of nerve-integrated muscle. The dawn of a new paradigm in the treatment of SUI may be near.     

Adipose tissue and lipid droplet embolism following periurethral injection of autologous fat: Case report and review of the literature

The authors present a case of a death associated with pulmonary adipose tissue and lipid droplet embolism following autologous fat harvesting, periurethral injection and videocystourethroscopy for the treatment of recurrent genuine stress incontinence.     

Applicability of regenerative medicine and tissue engineering for the treatment of stress urinary incontinence in female patients

Stress urinary incontinence (SUI) is an age health‐related issue that generates interest due to its considerable public health burden and the controversies surrounding treatment. It is highly prevalent affecting 30–40% of all women during their lifetime. Midurethral slings are the standard of gold standard treatment for female patients with SUI. They have excellent short‐term cure rates; however, their efficacy tends to decrease over time and patients often report urinary incontinence recurrence. This paper addresses the applicability of regenerative medicine and tissue engineering for the treatment of SUI in female patients. Cell‐based treatment with periurethral injection of autologous adipose or muscle‐derived stem cells have been used for SUI; however, the cure rates and SUI recurrence at 1 year were 40% and 70%, respectively. Novel minimally invasive approaches, such as low‐intensity extracorporeal shock wave therapies have shown promising results in SUI animal models. In addition, local injection of growth factors, chemokines, and specific antibodies have shown histological evidence of neoangiogenesis, nerve, and sphincter regeneration in rodents and nonhuman primates with SUI. The use of bioactive factors and proteins secreted by cells, which is called secretomes, have been recognized as key regulators of various mechanisms, such as immunomodulation, angiogenesis, inflammation, apoptosis, and tissue repair. Emerging therapies aiming to replace or restore tissues and organ functionality may improve the long‐term efficacy and in the near future may represent the standard of care for the treatment of SUI.     

Periurethral granuloma following injection with dextranomer/hyaluronic acid copolymer for stress urinary incontinence

Periurethral injection of bulk-enhancing agents provides a simpler and cost-effective therapeutic approach for stress incontinence in women. We report a case of periurethral granuloma secondary to dextranomer/hyaluronic acid (Dx/HA) copolymer injection. A 73-year-old woman with history of radiotherapy for cervical carcinoma at the age of 55 presented with stress urinary incontinence. She underwent periurethral injection of Dx/HA copolymer, and incontinence was resolved. At 4 months postoperatively, a 3–4 cm noninflammatory painless mass in the external genitalia was noted. Cystic images compatible with urethral diverticula were seen in the magnetic resonance imaging scan, but voiding cystourethrography was unrevealing. Transvaginal tumor puncture yielded abundant creamy material, the culture of which was negative. Microscopic examination revealed refractile foreign material surrounded by foreign body giant cells. Surgical debridement of the granuloma using a cold scalpel was performed. Stress urinary incontinence recurred but resolved spontaneously within 1 month. One year later, the patient continues to be asymptomatic.     

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.     

Treatment of Stress Urinary Incontinence in Women with Urethral Hypermobility and Intrinsic Sphincter Deficiency

Purpose

We compared 2 treatment modalities (sling cystourethropexy and periurethral collagen injection) in patients with intrinsic sphincter deficiency alone or with urethral hypermobility (combined stress urinary incontinence).

Materials and Methods

We retrospectively reviewed a series of 50 consecutive patients treated surgically for intrinsic sphincter deficiency during a 2-year period. All patients were evaluated by history and physical examination to assess urethral hypermobility and urodynamic testing. Intrinsic sphincter deficiency was assessed by abdominal leak point pressure and video urodynamics. Of the 50 patients 28 underwent a pubovaginal sling operation and 22 received a periurethral injection of collagen.

Results

Of the patients studied 40 percent had combined stress urinary incontinence. A pubovaginal sling procedure resulted in a cure rate of 81 percent in this group, compared to 25 percent for periurethral injection of collagen.

Conclusions

A subgroup of women exists with combined stress urinary incontinence due to urethral hypermobility and intrinsic sphincter deficiency. When treated with sling cystourethropexy women with combined stress urinary incontinence do as well or better than those with intrinsic sphincter deficiency alone and those treated with periurethral collagen injection do worse.     

Bulking agents for stress urinary incontinence: short-term results and complications in a randomized comparison of periurethral and transurethral injections

The purpose of our study was to compare the two standard routes of urethral bulking injection in a prospective randomized trial. Forty women with genuine stress incontinence (n=36), or mixed incontinence with a minor and controlled urge component (n=4), participated in a urethral bulking agent trial. All patients had a standardized preoperative evaluation which included history, physical examination, assignment of incontinence status on a Stamey grading scale, postvoid residual (PVR) determination, Valsalva leak-point pressure, maximal urethral closure pressure, functional urethral length, Q-tip excursion angle, quantitative pad test, and completion of a quality of life questionnaire. On the day of injection they were randomly assigned to a periurethral or transurethral route of injection based on a computer-generated block randomization scheme. An ultrasound-determined PVR was obtained on all patients after injection. If self-catheterization was necessary, and the PVR was >200 ml, urinary retention was diagnosed. Postoperative assessment included a patient interview, subjective assessment of improvement, PVR, voiding diary, and assignment of incontinence grade. At the screening visit there were no significant differences between the groups for any variables except type of stress incontinence. With short-term follow-up both transurethral and periurethral routes of injection seem to be equally efficacious. In the periurethral injection group there was a higher rate of postoperative retention; this group had a significantly higher volume of injectable agent used. There was no significant difference in risk of urinary tract infections between the two groups. We conclude that both periurethral and transurethral methods of bulking agent injection for stress urinary incontinence are equally efficacious, with minimal morbidity.Abbreviations FUL Functional urethral length - ISD Intrinsic sphincter deficiency - MUCP Maximum urethral closure pressure - PVR Postvoid residual - SUI Stress urinary incontinence - VLPP Valsalva leak-point pressureEditorial Comment: This pilot study is the first randomized controlled trial comparing the short-term efficacy of periurethral and transurethral injections. The poor 1-year success rates found in this study are disappointing if compared to other studies (showing up to a 70% success rate). In addition, owing to the small sample size and lack of power to find a statistical difference in efficacy rates, larger studies with longer follow-up periods are required.     

Comparison of the precision of transurethral endoscopic versus ultrasound-guided application of injectables

OBJECTIVE

To compare the precision of transurethral endoscopic‐ vs ultrasound (US)‐guided injections, as transurethral application of various injectables under endoscopic view are widely used to treat urinary incontinence.

MATERIAL AND METHODS

Bovine collagen was injected into the lower urinary tract in 20 dead female pigs. In each pig five depots of collagen were injected and there were five pigs in each group. In group I collagen was injected into the urethral wall under endoscopic control. In group II collagen depots were injected periurethrally under endosocopic guidance. In group III collagen was injected into the urethral wall under US control. In group IV collagen depots were injected periurethrally under US guidance. A transurethral US probe (6 F, 15 MHz) and injection device were used for transurethral US‐guided injections. In all pigs the urethra and the periurethral tissue were removed after injection and investigated using anatomical preparations and histological sections.

RESULTS

In group I only two collagen depots were actually located in the urethral wall in two pigs (two of 25 depots, 8%). In group II five depots in two pigs were located in the urethral wall (five of 25 depots, 20%). The periurethral collagen depots were found to spread out in the loose connective and fat tissue around the urethra. In group III all US‐guided injections of collagen were situated in the urethral wall and in group IV they were all located periurethrally.

CONCLUSIONS

The present study shows that endoscopic application of injectables is an inaccurate technique, while US‐guided injections are precise. US‐guided injection enables excellent control of the therapeutic procedure.     

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.     

肌源干细胞自体移植治疗压力性尿失禁的可行性研究

目的探讨鼠骨骼肌肌源干细胞(MDC)自体移植在压力性尿失禁治疗中的可行性。方法采用差速贴壁法分离、纯化培养6只雌性大鼠的MDC,体外脂质体介导法转染pEGFP-N1质粒入MDC,转染成功后将筛选的MDC注射于自体膀胱颈和尿道周围,5、15 d处死大鼠切取膀胱及后尿道,组织学检查观察注射组织形态学改善,免疫组化检测GFP蛋白的表达,观察MDC存活情况。结果5、15 d注射部位组织未见明显炎症改变及炎性细胞浸润,局部细胞层数增多,免疫组化显示各时间点大量细胞细胞质内可见棕黄色GFP蛋白表达,且在5、15 d两个时间点GFP阳性细胞数量和染色强度没有明显改变。结论MDC自体膀胱尿道周围注射可持续存活,自体MDC有可能成为治疗压力性尿失禁的一种理想材料。     

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.     

Preliminary results of myoblast injection into the urethra and bladder wall: a possible method for the treatment of stress urinary incontinence and impaired detrusor contractility

The purpose of this study is to explore the feasibility of myoblasts, the precursors of muscle fibers, injected periurethrally as a potential treatment of stress urinary incontinence. We also studied myoblast injection into the bladder wall to potentially improve detrusor contractility. A myoblast cell line was transduced with adenovirus carrying the expression of the beta-galactosidase reporter gene while in culture. The cells were incubated with fluorescent latex microspheres (FLMs) to follow the outcome of the injected cells. The tissue was harvested 3-4 days after injection; sectioned, fixed, assayed for beta-galactosidase expression, and counterstained with H+E. Photographs of the slides were taken under light and fluorescence microscopy. We have noted a large number of cells expressing beta-galactosidase and containing FLMs in the urethral and bladder walls under fluorescent microscopy (8 animals). Many regenerative myofibers expressing beta-galactosidase were also seen in the urethral and bladder walls. The fusion of injected myoblasts to form myotubes was seen in both the urethral and bladder walls. The introduction of myoblasts into the urethral and bladder wall is feasible and results in formation of myotubes and myofibers in the smooth muscle layers of the lower urinary tract. We hypothesize that myoblast injections can be used as a non-allergenic agent to enhance urethral closure and bladder function.     

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.     

Complications of teflon injection for stress urinary incontinence

Four significant complications of Teflon injections for stress urinary incontinence are reported in 22 women and eight men. Three of the complications included periurethral abscess, urethral diverticulum, and periurethral Teflon granuloma with urethral wall prolapse occurred in women. These complications needed surgical excision and further surgery for stress incontinence, in two patients the outcome was good. Among the female patients the cure rate for stress incontinence with Teflon injection was only 18% in the 5-year follow-up. One other complication, a Teflon cyst, occurred in a male who had previously undergone radical retropubic prostatectomy. Only two of the eight men (25%) who received Teflon injections had maintained improvement after 1 year.     

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.