Hypothesis / aims of study
Stress urinary incontinence (SUI) is a serious problem that affects 20% of adult women. According to the integral theory of continence, injury to the pubourethral and urethropelvic ligaments are the main causes of SUI. Current surgical techniques attempt to restore the urethra to the position prior to ligament damage, increase its resistance and improve its support. Periurethral injections increase urethral resistance. Platelet Rich Plasma with Fibrin (PRPF) is an injectable autologous substance with adhesive, haemostatic, and bulking characteristics. It has been shown to be useful in the repair of ligaments and musculoskeletal injuries[1]. PRPF has been used to repair vesico-vaginal fistulas and for the treatment of penile conditions[2].
Periurethral injections have been performed with autologous, heterologous and synthetic substances. PRPF is autologous, has very few known complications, and is relatively inexpensive. The theoretical concept of the use of PRPF for the treatment of SUI has already been described. An animal experiment confirmed the increase in urine leakage pressure after the application of periurethral PRPF[3] .
Periurethral injection of PRPF in females was described by Matz [2]. We describe our current technique and clinical pathway in female patients with SUI.
Study design, materials and methods
The clinical pathway includes pre-injection assessment for SUI, information on the procedure including options and possible risks and advantages. They’re also instructed on supra-pubic catheter (SPC) care including post-void residual (PVR) measurement. We obtain consent.
The preoperative assessment included history and physical examination, multichannel urodynamic studies and cystoscopy. We obtain a voiding diary, pad use, ICIQ-SF and UDI-6 questionnaires. Previous treatments (including pelvic muscle exercises) operations, radiotherapy, perineal sensation and anal sphincter tone are carefully assessed.
The PRPF is prepared with venous blood. This is centrifuged using a soft spin. The supernatant plasma containing platelets is separated into another sterile tube. This in turn, is centrifuged using a hard spin. The lower third of the tube contains PRP and the upper two thirds are discarded. Before injection PRP is activated with calcium to form a gel which is PRPF.
The injections are performed under general, spinal or local anaesthetic according to patient preference. We use prophylactic antibiotics. The vagina is prepared and draped as for a cystoscopy. If the procedure is done with local anaesthetic, we perform a periurethral block with 2% Lidocaine. The PRPF can be deployed by injections performed retrograde (trans-urethral or peri-urethral- Figure 1) or antegrade via a suprapubic access. The transurethral route allows for a precise site of injection but goes through the urothelial lining with the theoretical risk of infection and agent extrusion. The suprapubic access allows for endoscopic control without the cystoscope occupying the urethral lumen and it’s also used to leave a SPC. Additionally, an antegrade intraoperative perfusion manometry can be performed to measure intravesical pressure until urethral leakage stops.
The injection points we use are at 3, 6, 9 and 12 o’clock cystoscopic positions. 0.5 to 2 ml are injected at each site, to obtain urethral closure at the level of the sphincter, immediately increasing urethral resistance by extrinsic compression. If a SPC has been placed, the patient is discharged when recovered (or immediately, after local anaesthetic). If not, when she manages to void without a significant residual.
Results
Postoperative information includes return to physical activity, analgesia (which has been rarely required) and safety, including control for possible complications, for example infectious, embolism and early PRPF reabsorption. We perform a telephone follow up at day 3 and then at one month, 3 months, 6 months and annually. A voiding diary, pad use, ICIQ-SF and UDI-6 questionnaires are repeated at each contact.
All patients reported continence in the early weeks. The technique is easily reproducible both in the preparation of PRPF and the injection steps. We are currently prospectively following a cohort in 3 centres.
The procurement and preparation of PRPF is easy, accessible, reproducible, well tolerated and cost effective (at 15-20% of the cost of polyacrylate injections locally).
Interpretation of results
Our technique and pathway for PRPF injection are feasible, easy to learn and reproduce for a surgeon familiar with lower urinary tract endoscopy and anatomy. The cost favourably compares with other injectable alternatives.
PRPF autologous injectable is a possible alternative to other peri-urethral bulking agents. It additionally has the likely benefit of restoring and repairing the adjacent pubourethral and urethropelvic ligaments[1]. Therefore PRPF has tissue repair benefits that may well go beyond the simple compression of the urethra to improve continence.
The SPC allows for a rest period to the urethra and for the PRPF to settle in the injection sites.
It is probable that repeated injections will be necessary for the repair of ligaments over time. We make sure that local oestrogen supplementation is maintained when indicated.