|Year : 2022 | Volume
| Issue : 3 | Page : 233-238
Comparative study between the closure of small-sized and medium-sized urethral cutaneous fistula after hypospadias repair with and without autologous platelet-rich plasma graft
Abdelrahman Elsayed Kopeya, Ahmed A Elshamy, Mahmoud Abdelhady Moussa
Department of Pediatric Surgery, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
|Date of Submission||27-Dec-2021|
|Date of Decision||14-May-2022|
|Date of Acceptance||07-Jun-2022|
|Date of Web Publication||11-Oct-2022|
MBBCH Abdelrahman Elsayed Kopeya
Department of Pediatric Surgery, Faculty of Medicine, Al-Azhar University, Assiut
Source of Support: None, Conflict of Interest: None
Background and aim Many complications have been recorded after hypospadias repair surgeries. The most common one is the urethrocutaneous fistula (UCF). In this study, we aimed to compare the closure outcome of the small-sized and medium-sized UCF after hypospadias repair with and without autologs platelet-rich plasma (PRP) graft.
Patients and methods This is a prospective comparative study for managing UCF in the pediatric age group of over 1 year. They were randomly divided into two groups: group A included 20 patients who underwent repair without PRP and group B included 20 patients who underwent repair with PRP. Complication rates were compared between the two groups.
Results There was a significant difference in the occurrence of complications between the two groups. Recurrence of the fistula was observed in five cases, three (15%) in group A and two (10%) in group B. In group A, the three cases with fistula failed to be treated conservatively and needed another operation 6 months after the primary repair, while in group B, two cases were treated conservatively, and spontaneous closure of the fistula occurred while only one case required another operation for closure of the fistula. Postoperative infection was reported in two (10%) cases in group A and three (15%) cases in group B; they were treated using topical and systemic antibiotics. An extensive scar was reported in one case in group A.
Conclusion Autologs PRP graft could be used in hypospadias surgeries and the repair of post-hypospadias repair UCF as it is safe, easily applicable, and proven its role in decreasing complications.
Keywords: hypospadias, medium-sized urethrocutaneous fistula, pediatrics, platelet-rich plasma, small-sized urethrocutaneous fistula
|How to cite this article:|
Kopeya AE, Elshamy AA, Moussa MA. Comparative study between the closure of small-sized and medium-sized urethral cutaneous fistula after hypospadias repair with and without autologous platelet-rich plasma graft. Al-Azhar Assiut Med J 2022;20:233-8
|How to cite this URL:|
Kopeya AE, Elshamy AA, Moussa MA. Comparative study between the closure of small-sized and medium-sized urethral cutaneous fistula after hypospadias repair with and without autologous platelet-rich plasma graft. Al-Azhar Assiut Med J [serial online] 2022 [cited 2023 Jan 27];20:233-8. Available from: http://www.azmj.eg.net/text.asp?2022/20/3/233/358036
| Introduction|| |
Of all birth defects, hypospadias frequently comes with an incidence of one in 250–300 male births . Following surgery, many complications were reported, and many factors affecting the type and rate of complications such as hypospadias type, presence or absence of chordee, age of candidate, suture type, the chosen technique for repair, if catheter and magnifications present or not, type of dressing, use of covering layer over repair, and antibiotic administrations before and after the repair ,.
One of the most agonizing complications after hypospadias surgeries is the urethrocutaneous fistula (UCF), with an incidence of 4–20% . To overcome UCF, especially in recurrent cases, many modifications and improvements in surgical techniques have been applied over the last few decades. Currently, many approaches have been used to prevent and decrease the rate of recurrent post-hypospadias repair UCF, and most of them suggesting the use of another layer between urethroplasty and the skin. This layer could be the dartos fascia, which is the most commonly used, dartos flap from the penis, tunica vaginalis flap, or even extragenital tissue-like bladder mucosa and groin or free skin graft . On the other hand, fibrin sealant was proposed as a substitution of this tissue flaps in preventing UCF and improving wound healing. The use of fibrin glue could decrease the incidence of UCF formation. However, it did not eliminate the risk of UCF, as reported by Gopal et al. .
Platelet-rich plasma (PRP) is an autologs concentrate of human platelets in a small volume of plasma containing biologically active factors responsible for hemostasis, synthesis of new connective tissue, and revascularization . Amplifying blood clotting and inducing regeneration of tissues are the major benefits of using platelet concentrates. We use this concentrate as a coverage layer in soft tissue surgery. In addition to platelets, PRP also involves several important factors that amplify tissue regeneration . By supporting the synthesis of collagen and accelerating wound healing, PRP provides rapid angiogenesis and easier rearrangement of fibrin and collagen threads in more resistant tissues. That supports the use of this concentrate for all types of healing in all types of tissues ,.
This study aims to compare the outcome of closure of the small-sized and medium-sized UCF after hypospadias repair with and without an autologous PRP graft regarding operative time, postoperative complications, and recurrence UCF.
| Patients and methods|| |
This is a prospective, randomized controlled study for the management of UCF in the pediatric age group. This study was conducted on 40 patients with post-hypospadias UCF ranging from small-sized to medium-sized UCF. Patients were randomly classified into two groups: group A: 20 cases that underwent repair without autologous PRP graft. Group B: 20 cases that underwent repair with an autologous PRP graft.
The study was approved by the ethics committee of the Al-Azhar Assiut Faculty of Medicine, and informed written consent was obtained from all participants. The study was conducted in accordance with Helsinki standards as revised in 2013.
Patients presented with fresh UCF, post-hypospadias small UCF (<2 mm), and post-hypospadias medium-sized UCF (2–4 mm) were included in our study.
On the other hand, children were excluded if they had large UCF (>4 mm), were aged more than 10 years or less than 1 year, had a crippled fistula, small-sized penis, ambiguous genitalia, DSD, and associated blood diseases.
Platelet-rich plasma preparation
Fresh preparation of PRP was done intraoperatively. On the day of operation, 6–12 ml of blood was taken from the patient and immediately double centrifuged under complete aseptic condition. In the operating room, calcium gluconate was added, and the specimen was kept incubated for 4 min at 37°C. Based on the density of blood components, the specimen was differentiated into three layers: the bottom containing red blood cells while the middle layer containing PRP including platelets and white blood cells and the uppermost layer containing platelet-poor plasma ([Figure 1]).
We extracted the clot, separated it from the red blood cells, compressed it between two swabs, and finally, we managed to obtain a soft, resistant membrane ([Figure 2]).
In both groups, the repair was carried out for all patients, with a suitable size catheter (8–12 Fr), by a primary closure of fistula with Vicryl 5/0 round needle with a two-layer closure: first layer continuous subcuticular transverse and second layer interrupted transverse sutures. In group B, after finishing the repair, a PRP graft coverage was applied over and sutured by Vicryl 6/0, and finally, the skin was covered directly without any layers in between. In group A, no PRP was used ([Figure 3] and [Figure 4]). The patients received general anesthesia and caudal analgesia to minimize postoperative pain.
|Figure 3 The repair was carried out for all patients, with a suitable size catheter (8–12 Fr), by a primary closure of fistula with Vicryl 5/0 round needle with a two-layer closure: first layer continuous. subcuticular transverse and second layer interrupted transverse sutures.|
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Data were analyzed using SPSS Inc. (Chicago, Illinois, USA), version 23.0. Quantitative data were presented as mean±SD when their distribution was parametric. Also, qualitative data were presented as numbers and percentages. Data were explored for normality using Kolmogorov–Smirnov and Shapiro–Wilk test. P value less than 0.05 was considered significant. As we did not find another previous similar study, so e took a convenient sample, including any patient we could get in our study period. So our study may be considered as a pilot or initial study for another future larger study.
| Results|| |
Fourteen cases who had UCF were included in our study. Twenty patients underwent repair without PRP, and 20 patients underwent repair with an application of PRP graft over the repair. The mean age of the patient in group A was 3.32±1.87, while in group B was 5±2.05. This study was conducted in the Department of Pediatric Surgery at Al-Azhar University. The UCF post-hypospadias repair is more common after anterior penile hypospadias. According to the site of UCF, the anterior penile fistula was more popular than the mid-penile fistula, in which 32 (80%) patients presented with anterior penile fistula while just eight (20%) patients having presented with mid-penile fistula ([Table 1]). The operative time of group A (without PRP graft) is 46.25 min±7.58 as SD, which is less than the mean operative time of group 2 (with PRP graft), which is 67.5±15.76 min as SD with a significant P value less than 0.001 ([Table 2]).
However, the all over complication rate and the need for another operation were lower in group B (with PRP graft) than group A (without PRP graft). Postoperative infection was reported in three (15%) cases in group A and two (10%) cases in group B. The infection was noticed after uncovering of dressing on the fifth day with redness, hotness, and grayish discoloration. One case in group A was discharging pus, which was submitted to culture and sensitivity and treated with suitable antibiotics both topically and systemically; unfortunately, disruption of the wound occurred. In the other four cases, just a change of the antibiotic succeeded in resolving the infection:
- Fistula recurrence: in our study, we removed the catheter seventh-day postoperatively and 2 days after uncovering of dressing. In group A, we reported three (15%) cases, and two (10%) cases were reported in group B with postoperative fistula, which was first noticed by the dripping of urine just after extraction of the catheter, and with time it became a complete stream. The three cases with fistula in group A failed to be treated conservatively, and recurrence of the fistula, which was nearly the same size as the original fistula, was confirmed after 4 weeks of follow-up and needed another operation 6 months after the primary repair, while in group B the two cases were treated conservatively (usually with hyaluronic acid, topical and systemic antibiotics) and spontaneous closure of the fistula occurred in one case while the other case required another operation for closure of the fistula.
- Complete disruption occurred only in one case in the group after an extensive postoperative infection had occurred; no disruption occurred in group B.
All cases have a good stream of urine without spraying or difficulties.
| Discussion|| |
The hypospadias repair surgeries are numerous, and a lot of modifications and advancements were adopted by genius surgeons to minimize the complications and get satisfactory results . However, some of these techniques may lead to unsuccessful repair despite the use of proper magnifications, suitable suture types, fine needles, and other suggested precautions. UCF frequently comes after hypospadias repair with an incidence of 4–20% .([Table 3])
A lot of basic factors were described to get ideal repair of these UCF, which are avoiding operation on inflamed tissues, overcome of distal stenosis, using absorbable suture material to obtain a tension-free urethral closure, and using a covering layer over the repair . In this study, we compared two simple techniques used in treating UCF. In this study, the anterior penile region was the most common site of UCF in our 40 cases (32 of 40 cases, 80%). The site of the coronal sulcus is the most difficult site of healing after hypospadias repair surgeries due to its poor vascularization and its location between the glans and corpus penis. While performing the repair, excessive penile skin, and urethral plate dissection highly affect vascularization, especially in older children; postoperative erections may induce the ischemia in the coronal sulcus, and increase the fistula formation and recurrence, which create serious problems in the healing process .
In seeking better outcomes of hypospadias repair surgery and decreasing the rate of UCF, many surgical techniques have been described, and the most recent trends agree that placing an intermediate layer between repair and the overlying skin is the optimum way to overcome unwanted complications . Savanelli et al.  used the dartos flap in the repair of distal penile hypospadias and noticed the decrease of incidence of fistula compared with the patients that did not. Yilmaz et al.  clarified the role of fistula size and the effect of placing one or two well-vascularized tissue flaps on the success of repair of UCF post-hypospadias repair
As observed from these studies, the most important factor that affects the repair of fistula and also primary repair of hypospadias is the use of not only a single layer between repair and skin, as by increasing the number of layers, the risk of recurrence of fistula decreases.
Gopal et al.  suggest using fibrin glue in minimizing the risk and rate of UCF, which complicates hypospadias repair surgery, but unfortunately, and despite the good beneficial effect of these biological materials, they could not eliminate the risk of UCF completely.
PRP is known as an autologous plasma fraction with a high concentration of platelets. Being a biological binder that connects the underlying tissues and the skin (in a way similar to fibrin glue), and acceleration and improvement of healing of tissues by stimulation of proliferation of skin and connective tissue are the main functions of using PRP in this issue. It also acts as a protective layer that protects a site of surgery by avoiding local skin necrosis and improving wound healing  as autologs platelets are rich in cytokines and platelet-derived growth factors, which will help to achieve better wound healing . Platelet’s main function is to activate the coagulation cascade, which decreases intraoperative and postoperative bleeding. It also contains platelet-derived growth factors and cytokines that accelerate wound healing. At the site of the surgery, PRP releases high concentrations of cytokines and growth factors that promote wound healing. It also helps in the differentiation and migration of primitive connective tissue cells leading to much better healing .
In this study, we followed the method used by Mahmoud and colleagues in preparing PRP as they used it in patients with distal hypospadias and found that the incidences of complications and UCF in the PRP group were 13.3%, and the non-PRP group was 26.7%, and recommend the use of PRP as an alternative coverage layer for distal hypospadias repair surgeries ,.
Our study provides a safe, inexpensive, easily applicable treatment for UCF. However, we have some limitations, such as difficult sample size calculations, uncooperative patient families, short follow-up periods, and the absence of another previous similar study.
| Conclusion|| |
Autologous PRP graft could be used not only in hypospadias surgeries but also in the repair of post-hypospadias repair UCF as it is not expensive, safe, easily applicable, and has proven its role in decreasing postoperative complications.
More studies with a larger sample size and more extended periods of follow-up are needed to support our findings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Koyle MA. Hypospadias: a 30-year personal journey. Scand J Surg 2011; 100:250–255.
Kanaroglou N, Wehbi E, Alotay A, Bagli D, Koyle M, Lorenzo A, Farhat W. Is there a role for prophylactic antibiotics after stented hypospadias repair?. J Urol 2013; 190(4S):1535–1539.
Sarhan OM, El-Hefnawy AS, Hafez AT, Elsherbiny MT, Dawaba ME, Ghali AM. Factors affecting outcome of tubularized incised plate (TIP) urethroplasty: single-center experience with 500 cases. J Pediatr Urol 2009; 5:378–382.
Santangelo K, Rushton HG, Belman AB. Outcome analysis of simple and complex urethrocutaneous fistula closure using a de-epithelialized or full thickness skin advancement flap for coverage. J Urol 2003; 170(4 Part 2):1589–1592.
Cimador M, Castagnetti M, De Grazia E. Urethrocutaneous fistula repair after hypospadias surgery. BJU Int 2003; 92:621–623.
Gopal SC, Gangopadhyay AN, Mohan TV, Upadhyaya V, Pandey A, Upadhyaya A, Gupta D. Use of fibrin glue in preventing urethrocutaneous fistula after hypospadias repair. J Pediatr Surg 2008; 43:1869–1872.
Marx RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP?. Implant Dent 2001; 10:225–228.
Scarcia M, Maselli FP, Cardo G, Ludovico GM. The use of autologous platelet rich plasma gel in bulbar and penile buccal mucosa urethroplasty: preliminary report of our first series. Arch Ital Urol Androl 2016; 88:274.
Sunitha Raja V, Munirathnam Naidu E. Platelet-rich fibrin: evolution of a second-generation platelet concentrate. Indian J Dent Res 2008; 19:42.
Choukroun J, Diss A, Simonpieri A, Girard M, Schoeffler C, Dohan S, Dohan A, Mouhyi J, Dohan D. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part IV: clinical effects on tissue healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 2006; 101:e56–e60.
Goel P, Jain S, Bajpai M, Khanna P, Jain V, Yadav D. Does caudal analgesia increase the rates of urethrocutaneous fistula formation after hypospadias repair? Systematic review and meta-analysis. Indian J Urol 2019; 35:222.
Waterman BJ, Renschler T, Cartwright PC, Snow BW, DeVries CR. Variables in successful repair of urethrocutaneous fistula after hypospadias surgery. J Urol 2002; 168:726–730. discussion 729–730.
Elbakry A. Management of urethrocutaneous fistula after hypospadias repair: 10 years’ experience. BJU Int 2001; 88:590–595.
Guinot A, Arnaud A, Azzis O, Habonimana E, Jasienski S, Frémond B. Preliminary experience with the use of an autologous platelet-rich fibrin membrane for urethroplasty coverage in distal hypospadias surgery. J Pediatr Urol 2014; 10:300–305.
Savanelli A, Esposito C, Settimi A. A prospective randomized comparative study on the use of ventral subcutaneous flap to prevent fistulas in the Snodgrass repair for distal hypospadias. World J Urol 2007; 25:641–645.
Yilmaz Ö, Okçelik S, Soydan H, Ateş F, Yeşildal C, Aktaş Z, Şenkul T. Our urethrocutaneous fistula repair results in adults after hypospadias surgery. Rev Int Androl 2018; 16:143–146.
Mishra A, Woodall J, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med 2009; 28:113–125.
Hong SH, Nam J, Kim HJ, Yoo JJ. Platelet-rich plasma pretreatment on grit-blasted titanium alloy for enhanced osteogenic differentiation of human adipose-derived stem cells. Clin Orthop Surg 2019; 11:361.
Mahmoud AY, Gouda S, Gamaan I, Baky Fahmy MA. Autologous platelet‐rich plasma covering urethroplasty versus dartos flap in distal hypospadias repair: a prospective randomized study. Int J Urol 2019; 26:475–480.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]