SURGICAL MANAGEMENT OF UI AND PELVIC PROLAPSE: 2006 AUA RESULTS

David Ginsberg, MD

The Minimally Invasive Sling for Treatment of Stress Urinary Incontinence (SUI) in Patients With Failed Anti-SUI Procedure

Minimally invasive slings (MIS) have become a well-accepted method of therapy for patients with SUI. Early studies regarding these procedures often focused on patients who had not had prior anti-SUI surgery. The efficacy of MIS for the treatment of SUI after a failed anti-SUI is not known. Anoia and colleagues[1] examined their outcomes in patients undergoing a MIS procedure who had a prior sling and presented with recurrent SUI. Outcomes in 170 patients undergoing a primary MIS who did not have a prior sling for SUI were compared with outcomes in 44 patients undergoing a secondary MIS who did have a prior sling surgery attempt at treating SUI. Compared with the primary group, patients who had a secondary MIS at baseline required more pads/day (4.8 vs 2.9, P < .001), had more daily incontinence episodes (6.3 vs 4.2, P < .008), had a greater 24-hour pad weight (310.4 g vs 135.2, P = .005) and a lower Valsalva leak point pressure (VLPP, 42.6 vs 69.3 cm H20, P < .001). Cure was defined as 0 pads/day or 1 pad/day for protection only. Cure rates were essentially equivalent: 91.8% for primary MIS and 87.5% for secondary MIS. The secondary MIS procedures were further broken down into 2 subgroups, comprising 35 patients who underwent a synthetic sling and 9 patients who underwent a biologic sling. Cure rates were equivalent between these 2 subgroups. In addition, cure rates were not affected by the type of sling done previously, with essentially equal rates between a traditional bladder neck sling to a sling placed mid-urethrally. All of the patients who failed in the secondary MIS group had a VLPP < 30 cm H20.

The authors concluded that a MIS can be used in the setting of recurrent SUI after prior failed sling. This is an important point. In the past it was not unreasonable to suggest that patients undergo autologous fascial sling for a prior failed sling. These data suggest that at least 1 attempt with a second MIS is reasonable for this patient population. The equivalence of outcomes between the 2 groups is even more impressive considering that the secondary MIS group had a statistically significant worse degree of SUI compared with the primary MIS group. Patients with a lower VLPP (< 30 cm H20) should be cautioned that they have a lower chance of success compared with patients with higher VLPP (58.3% vs 87.5%). It was not stated which MIS the authors used, though it appeared from the presentation that a variety of biologic and synthetic sling kits were used. The likelihood of successful outcome with MIS for patients who have had multiple prior failed sling attempts to surgically correct SUI remains unknown.

Injectable Stem-Cell Therapy for SUI

Currently available injectable therapy for SUI helps only approximately 65% of patients treated, with even lower cure rates. Other potential downsides of available urethral bulking agents include the need for multiple injections to obtain (and then maintain) optimal efficacy, potential antigenicity of the injectable and allergic reaction, migration of injected material, and urethral pain both at the time of injection and afterward. For these reasons, the search for a superior injectable for therapy for SUI continues.

Stem cells are being evaluated as a potential injectable therapy for SUI. The largest series to date was presented by Strasser and colleagues,[2] who evaluated the safety and efficacy of using autologous stem cells. Cells were harvested from small skeletal muscle biopsies from the upper arm and after appropriate preparation were injected into 130 patients with SUI. Fibroblasts were injected into the urethral submucosa, and myoblasts were injected into the rhabdosphincter using a transurethral ultrasound probe and a specially designed injection device. The authors quoted a cure rate of 85% (111 of 130 patients), with cure defined as the use of no pads daily. When questioned after the presentation, the authors stated that preoperatively patients required, on average, approximately 4 pads/day. No side effects, complications, or other safety issues were noted. This is an exciting first step towards the use of stem cells for the treatment of SUI. However, these data still need to be replicated by other authors. In addition, some of the data obtained by this group were not fully examined, such as pre- and postinjection urodynamic data and quality-of-life results.

Other investigators reported findings of studies evaluating the use of stem cells for SUI. Carr and colleagues (presented by Dr. Mike Chancellor)[3] reviewed an early Canadian experience injecting muscle-derived stem cells in 7 patients. Success was noted in 5 patients without any evidence of safety issues. Several animals models were evaluated in the United States. Zeng and colleagues[4] injected smooth muscle-differentiated adipose-derived stem cells into a nude rate model with SUI. The authors noted improvement of urethral resistance and restoration of urethral function and smooth muscle contractility, suggesting that this technique is not only able to "bulk" the tissue but also allows for improved urethral function. Finally, Eberli and colleagues[5] achieved similar results using muscle progenitor cells in a dog model.

The potential use of stem cells as an injectable for the therapy of SUI is very exciting. Several questions need to be answered before this can be used on a regular basis. Can the techniques required to obtain and subsequently grow cells be done easily enough to allow for commercial use? Early data in humans from Europe and Canada have not revealed any significant safety issues, but is it safe? Is it efficacious? The data presented above by Strasser and colleagues are outstanding, though other groups have yet to duplicate their success. In addition, longer follow-up will be required to get a better idea of the durability of these results. The most important question is, how does this work? If the stem cells are behaving just like other injectables and are bulking the urethra, it would be hard to imagine results being much different over time. It would be ideal if the stem cells were able to differentiate appropriately, leading to regeneration of the urethral wall (in particular the rhabdosphincter), allowing for improved urethral coaptation and improved urinary continence. Early animal data suggest that this may be the case. If so, this would allow for an actual treatment of the defect causing SUI and ultimately (and hopefully) a long-term cure.

Prolene Tape Slings

The discussion regarding the management of SUI has evolved over the past several years at the annual American Urological Association meeting. When mid-urethral synthetic (Prolene tape) slings were first introduced, there was an initial period of hesitancy before their use was embraced. Recent studies have more commonly compared synthetic slings with biologic slings (ie, cadaveric fascia or dermal grafts). With the evolution of mid-urethral Prolene tape slings, we now have many different techniques available, with options that include approach (suprapubic vs transobturator) and starting point of the needle (inside vs outside the vagina).

Andonian and colleagues[6] prospectively evaluated the outcome of tension-free vaginal tape (TVT; Gynecare; Somerville, New Jersey), transobturator tape (TOT; ObTape; Mentor; Santa Barbara, California), and the distal urethral Prolene mesh sling (Raz sling) as described by Dr. Shlomo Raz.[7] A total of 190 patients were randomized to TVT (n = 80), TOT (n = 78), or the Raz sling (n = 32). Preoperatively, patients in all 3 groups were comparable in terms of age, grade of incontinence, and type of SUI as well as pad test weight. The Raz sling was prematurely discontinued due to a higher initial postoperative urinary retention rate (18.8% for Raz sling vs 9.4% for TOT and 12.5% for TVT) and 2 immediate complete failures. Urinary retention rates at the end of the study for the 3 procedures were 18.8% for the Raz sling, 7.8% for TOT, and 7.5% for TVT. Bladder perforations occurring intraoperatively were noted in 14% of patients undergoing TVT; bladder perforation was not noted with the other 2 procedures. The TOT and the Raz sling were associated with more postoperative complications compared with TVT, with rates of 13%, 28%, and 8%, respectively (P ≤ .025). These complications included urinary retention requiring urethrolysis, hematoma, mesh erosion, urinary tract infection, and superficial wound infection. At 1-year follow-up, the cure (cure = 1-hour pad test ≤ 2 g) rate for the 3 procedures was 83% for TOT, 94% for the Raz sling, and 86% for TVT. There were no statistical differences in terms of cure between the 3 procedures.

Kocjancic and colleagues[8] prospectively compared the outcome of TVT vs TOT. A total of 90 patients were randomized: 47 to TVT and 43 to TOT. Preoperatively there were no differences between the 2 groups. Postoperative follow-up was similar between the 2 groups (average of 13.4 months) as was operating time, recovery to normal micturition, hospital length of stay, and number of intraoperative complications. Outcomes were evaluated subjectively (history and self-report questionnaires that classified patients as dry, improved, or failed) and objectively (examination and urodynamic stress test that classified patients as dry or wet). Subjective evaluation revealed dry and improved rates of 78.6% and 21.4%, respectively for TOT, and 70.2% and 19.1%, respectively for TVT. Objective success was noted at a rate of 97.6% for TOT and 93.6% for TVT. Preoperative urgency symptoms improved in 82.6% of TOT-treated patients and 47.6% of TVT-treated patients. The authors noted that this may suggest that patients with mixed incontinence do better with TOT, as urgency symptoms responded better in that cohort compared with patients undergoing TVT. There was no difference in the rate of late complications between the 2 groups. Late complications included vaginal erosion of mesh, voiding dysfunction, wound discomfort, foreign-body granuloma, and paraincisional hernia.

The abstracts by Andonian and colleagues[6] and Kocjancic and colleagues[8] do an admirable job in their attempts to compare the various types of Prolene slings available today. Neither of these studies is perfect. For example, the higher early retention rate for the Raz sling in the Andonian study may be explained by the fact that catheters were removed immediately in that study, but Dr. Raz and his group[7] tended to leave catheters in for a day or 2 before removing them. Although the overall complication rates may be a bit different, the rate of major complications is similar for all procedures. The important message from these 2 studies is that the outcomes in terms of cure rate of SUI are similar between the various procedures. Thus, surgeons should continue to use the procedure that they are most comfortable with and which would thus be most likely to provide an optimal outcome. Future studies will be welcomed, as both of these studies had follow-up out to approximately 1 year. As we continue to follow these patients out for 5 years and longer, it will be interesting to see whether there is any difference in the maintenance of SUI cure between these procedures. The other question that needs to be answered is whether certain procedures are better for certain patients. During one of the sessions, the moderator, David Staskin, asked the audience whether they performed different procedures on the basis of the severity of leakage. From a show of hands, it was apparent that many of the attendees in the audience tend to shy away from the TOT approach (or perform the procedure but adjust the tape a bit tighter) in patients with lower VLPP. The search for the perfect sling continues. As studies like the 2 just reviewed mature, we can gain a better understanding of how well these procedures withstand the test of time, which procedure is best, and whether certain procedures are better or worse for certain types of patients.

References

  1. Anoia EJ, Borawski KM, Amundsen CL, Webster GD. Minimally invasive sling as secondary procedures for recurrent stress urinary incontinence. Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 1183.
  2. Strasser H, Marksteiner R, Margreiter E, et al. Transurethral ultrasound guided stem cell therapy of urinary incontinence. Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 328.
  3. Carr LK, Steele D, Steele S, et al. Muscle derived cell injection technique to optimize the treatment of stress urinary incontinence. Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 1185.
  4. Zeng X, Jack GS, Zhang R, Wu B, Rodriguez LV. Treatment of SUI using adipose derived stem cells: restoration of urethral function. Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 900.
  5. Eberli D, Yoo JJ, Soker S, Atala A. Muscle progenitor cells for the restoration of irreversibly damaged sphincter function: a pre-clinical study. Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 329.
  6. Andonian S, St-Denis B, Lemieux MC, Corcos J. Randomized clinical trial comparing TransObturator Tape (Obtape), prolene mesh sling (Raz' Sling) and Tension-free Vaginal Tape (TVT): Safety and one-year efficacy. Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 333.
  7. Rodriguez LV, Raz S. Polypropylene sling for the treatment of stress urinary incontinence. Urology. 2001;58:783-785.
  8. Kocjancic E, Costantini E, Giannantoni A, Crivellaro S, Frea B, Porena M. Tension free vaginal tape vs trans obturator tape as surgery for stress urinary incontinence: results of a multicentre randomised trial. Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 899.