Abstract
Abstract
Introduction
A few studies with a limited number of patients applied fibrin glue (FG) for the treatment of vesicovaginal fistula (VVF),2–5 but this is the first report of UVF treatment using autologous platelet-rich plasma (PRP) and platelet-rich fibrin glue (PRFG).
Case
A healthy 32-year-old woman came to an obstetrics and gynecology service with obstructed labor. A cesarean section was performed and a 16-F Foley catheter was inserted into the patient after the operation.
The catheter was removed the next day. After 8 days, the patient complained about leakage, especially at night. Urethroscopy showed a fistula in the midurethra of ∼5 mm. International Consultation on Incontinence Questionnaire-Urinary Incontinence (ICIQ-UI) and ICIQ-Quality of Life (ICIQ-QOL) surveys were administered, and a complete transvaginal examination, routine laboratory tests
The study protocol and informed consent forms were reviewed and approved by the Human Research Ethics Committee of Mashhad University of Medical Sciences. The patient signed that form, and one of the surgeons explained all procedures and processes to her.
Autologous platelet-rich plasma (PRP) and platelet-rich fibrin glue (PRFG) preparation
The Hamidi–Shirvan method was used in this case.
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The procedure steps were as follows:
(1) One day before the operation, 60 mL of peripheral blood was taken in 9 mL of citrate phosphate dextrose buffer. (2) PRP was prepared by first centrifugation at 2000 g for 2 minutes, and then by second centrifugation at 4000 g for 8 minutes, and the supernatant plasma was separated and 4 mL PRP was initially separated.6,7 Next, 2 mL was kept as PRP to inject around the fistula, and the other 2 mL of PRP was mixed with 2 mL of fibrinogen concentrate (which is explained in step 3) to make the platelet-rich fibrinogen plasma (PRFP; final volume: 4 mL). (3) The fibrinogen concentrate was prepared from the separated plasma (step 2) by two biochemical methods: cryoprecipitating or ethanol precipitation.
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With the cryoprecipitation method, following a −70°C freeze and a 4°C thaw, plasma was centrifuged at 6500 g for 5 minutes. The supernatant plasma was separated to a final volume of 2 mL. With the ethanol precipitation method, absolute ethanol at 0°C was added to the plasma (10% v/v), and fibrinogen was collected by centrifugation at 6500g for 15 minutes and supernatant plasma (fibrinogen-poor plasma) was separated to a final volume of 2 mL. (4) For thrombin preparation, 400 μL of 10% calcium gluconate was added to 10 mL of fibrinogen-poor plasma (the separated plasma in step 3). (5) After 45 minutes, a clot formed; it was shaken vigorously and centrifuged at 4000 g for 2 minutes, and 1 mL of supernatant plasma, which contained thrombin, was separated. (6) For thrombin-calcium solution preparation, 100 μL of 10% calcium chloride was added to 1 mL of supernatant plasma, which contained thrombin (step 5). (7) For PRFG preparation, 4 mL of PRFP was mixed with 1 mL of thrombin-calcium solution during the operation time.
PRP injection and PRFG interposition to UVF tract
One g of cephazolin was administered intravenously 1 hour before the operation. With the patient under general anesthesia and in a lithotomy position, the exact location of the fistula was determined transvaginally and transvesically. A guide wire was inserted transvesically via the fistula; the ureteric orifice was identified to avoid damage. Prior to the application of PRP and PRFG, de-epithelialization was performed mechanically by a blade (Number 15) around the fistula transvaginally until a small amount of hemorrhage occurred. Then, the guide wire was removed, and 2 mL of PRP was injected transvaginally around the fistula into the tissue. In a 5 mL syringe, 4 mL of PRFP and 1 mL of thrombin-calcium solution were mixed. The mixture was slowly injected into the tract within 5 minutes, using a needle (G18), before it clotted. Some of the mixture could flow into the bladder or drop from the tract into the vagina, but it mainly remained in the tract. The operation took ∼15–20 minutes. The clot formation took ∼5 minutes, but the anesthesia was extended to 30 minutes to ensure that there was a complete clot in the fistula tract. Then, a Foley catheter was introduced into the patient for 7 days. Cephalexin tablets were prescribed, to be taken until 5 days after the catheter removal. After the catheter removal, as the area was dried completely and the patient was satisfied, transvaginal physical examination was not performed until 3 months later, in order to avoid any physical damage. At 3 months' follow up, transvaginal physical examination and cystography were normal. The outcome was measured according to the ICIQ-UI and ICIQ- QOL at 10 days, and 1, 3, and 6 months after catheter removal.
Results
There was no morbidity during and after the procedure, and, at the time of catheter removal, the patient was completely dry. Transvaginal physical examination and cystography were normal at 3 months' follow-up. At the baseline, ICIQ-UI and ICIQ-QOL were 20 and 34, respectively. After catheter removal, ICIQ-UI was 0, 0, 0, and 0 and ICIQ-QOL was 84, 92, 98, and 103, at 10 days, and 1, 3, and 6 months' follow-up, respectively.
Discussion
This is the first reported case of UVF closure with a mixture of autologous PRP and PRFG, which is safe and effective, after a single injection. The vaginal surgical approach is used in almost all cases of UVF repair. Closure is normally performed by primary anatomical closure or with the use of a tissue flap such as a Martius flap or rectus abdominal flaps, where primary repair is not achievable. 1 FG forms a fibrin clot, which is approximately 10 times stronger than a physiological clot. This clot provides a strong provisional matrix, and promotes local proliferation, ingrowth of fibroblasts, and collagen synthesis. 9 Watertight closure with FG prevents urinary extravasation, and reduces the risk of postoperative infection. 10 In PRP, bioactive factors are in the α-granules and the dense granules of platelets. The α-granules contain growth factors such as transforming growth factor–β, platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor, vascular endothelial growth factor, and endothelial cell growth factor. These growth factors play important roles in tissue regeneration. The dense granules contain serotonin, histamine, dopamine, calcium, and adenosine. These non-growth factors have fundamental effects on the biologic aspects of tissue repair. Also, PRP has an antimicrobial activity. 11 The additional value of this procedure is the application of autologous FG instead of allogenic FG, which decreases the expenses, and prevents blood-borne diseases that can be transmitted via the commercially available FG.
Conclusions
Considering the simplicity of the technique, minimal blood loss, low postoperative morbidity, and shorter time for the operation and postoperative recovery, it is suggested that surgery should be performed as the last resort when FG application method fails. This technique (Hamidi-Shirvan method 6 ) should be used in other centers to reconfirm its efficacy in UVF repair.
Footnotes
Acknowledgments
This case report was supported by the Mashhad University of Medical Science Research Council. Finally, written informed consent was obtained from the patient for publication of this case report and these procedures. The first two authors contributed equally to this case report.
Disclosure Statement
No competing financial interests exist.