Post-urethroplasty complications in hypospadias repair: a systematic review and meta-analysis comparing polydioxanone and polyglactin sutures

Introduction

Hypospadias is one of the most frequent birth defects affecting the male urethra. The prevalence of hypospadias varies across countries ranging from 2.1 to 39.1 per 10 000 live births.1 Aberrant ventral placement of the urethral meatus is characteristic of hypospadias. The anomalous urethral meatus can be located anywhere between the perineum and the tip of the glans penis. Depending on the anatomical location of the meatus, hypospadias can be categorized as glanular, penile, proximal, and perineal.2 The Hypospadias International Society recommends the meatus–chordee–glans width and shape-urethral plate quality score to describe the severity of hypospadias. The score ranges from 0 (normal) to 10 (perineal hypospadias with severe chordee, small glans, and narrow urethral plate).2 The English literature describes more than 300 methods of hypospadias repair.3 Satisfactory reconstruction should provide a cosmetically pleasant straight phallus with a vertically slit meatus at the glans tip. Despite technical developments such as the use of magnification and improvisation of the surgical equipment, urethrocutaneous fistula (UCF) remains the most frequent complication following hypospadias correction. The occurrence of UCF ranges from 7.5% to 50%, depending on the surgical repair technique and the severity of hypospadias.4 The UCF can develop anywhere across the length of the repair. Creating an intermediate protective layer to cover the neourethra has reduced the incidence of UCF in hypospadias repair. This protective intermediate layer can be fashioned using the de-epithelialized local skin, tunica vaginalis flap, local dartos, and free tunica vaginalis graft.5–8 Delicate tissue handling, use of bipolar diathermy, and microsurgical techniques also reduced the incidence of UCF in these patients.

One of the key factors affecting the complications following hypospadias repair can be the choice of the suture material. The use of absorbable sutures for hypospadias surgery is widely agreed upon among surgeons. However, choosing any particular suture material has always been a matter of individual preference. The ideal suture material used for neourethra construction should provide sufficient mechanical support and resist the chemical effect of urine until satisfactory wound healing. Polyglactin (PG) and polydioxanone (PDS) are the two widely used absorbable sutures for hypospadias repair. PG is a synthetic, braided, absorbable suture made of a copolymer of glycolide and lactide. It has a predictable and reliable absorption rate, typically lasting 4–6 weeks. PG is widely available, easy to handle, has good knot security, and is cost-effective. The drawback is intense tissue inflammation, higher capillarity, and tissue drag and trauma by its rough surface.9 PDS is another synthetic, absorbable suture made of a monofilament polymer of p-dioxanone. It has a slower absorption rate, lasting up to 6 months, which may provide more long-term wound support. PDS sutures are preferable for repairing delicate and high-tension wounds due to minimum tissue reaction, lower tissue drag, and minimal capillarity leading to fewer suture-related complications.9 On the other hand, they are more expensive than PG and may be less widely available.

Few studies indicated that PDS might not be suitable for urethral and penile reconstruction but other studies found that it provides better tissue support for wound healing. Guarino et al., in a comparative study of suture materials in hypospadias repair, observed a higher rate of pinpoint fistulae in the PDS group on long-term observation.10 The development of UCF was attributed to the prolonged absorption time of PDS. On the contrary, Ulman et al. reported a lower complication rate with subcuticular PDS compared with interrupted suturing with PG in hypospadias repair.11 Other studies that compared PDS and PG in hypospadias repair also failed to reach a precise conclusion. Studies by Khalid et al.9 and Cimador et al.12 reported no discernible variation in the frequency of UCF while using PG and PDS. Mohamed Ali Alaraby et al.,13 Fakhr,14 and Shizari et al.15 reported reduced complications with PDS. The inconsistent outcomes of the comparative studies on the choice of suture materials in hypospadias repair led to the planning of this systemic review and meta-analysis. This meta-analysis intends to evaluate postoperative complications following a urethroplasty using PG or PDS during hypospadias repair.

Methods

Results

Study characteristics

Following the literature search, a total of 161 studies were identified. The search and selection procedure is depicted in the PRISMA flow diagram (figure 1). A total of 111 records were examined by title and abstract after the elimination of duplicate studies. Fifteen articles were shortlisted for full-text screening, of which only five research articles9 12–15 were considered for the final quantitative analysis. The study characteristics of the included studies are summarized in table 1. The five studies included 1244 children, with 532 in the PDS group and 712 in the PG group. The study outcomes are summarized in table 2.

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Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram.

Table 1

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Characteristics of included studies

Table 2

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Summary outcomes

Meta-analyses of the complications

Urethrocutaneous fistula

Four studies have described this complication. There were 49 (9%) UCFs among 532 patients with PDS, while 87 (12%) UCFs were identified among 712 patients in the PG group. Pooled analysis (figure 2A) of this complication shows a statistically significant reduction in the incidence of UCF with PDS compared with PG, though with moderate heterogeneity (p=0.01, RR=0.66, 95% CI=0.48 to 0.92, I²=52%).

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Figure 2

Forest plots depicting: (A) Urethrocutaneous fistula; (B) Meatal stenosis: (C) Stricture; (D) Wound infection; (E) Total complications. PDS, polydioxanone; PG, polyglactin; UCF, urethrocutaneous fistula.

There is heterogeneity in the technique of hypospadias repair among the included studies. Heterogeneity also exists in the type of hypospadias. Studies by Khalid et al.9 and Fakhr14 included only anterior hypospadias. In contrast, Cimador et al.,12 Mohamed Ali Alaraby et al.,13 and Shirazi et al.15 included all types of hypospadias for the comparative analysis. Cimador et al12 used Mathieu transverse preputial tubularized flap and onlay technique, while Khalid et al.9 and Shirazi et al.15 used the Snodgrass technique to repair hypospadias. Mohamed Ali Alaraby et al.13 used meatal advancement and glanduloplasty, Mathieu, tubularized incised plate (TIP), and Thiersch-Duplay techniques for hypospadias repair. Fakhr14 did not mention the repair technique in their patients. This heterogeneity among the different studies may be insignificant as there is no heterogeneity among the PDS and PG groups in the included studies.

We conducted a subgroup analysis of the studies that exclusively used the TIP technique for the outcome analysis of UCF. Khalid et al.9 and Shirazi et al.15 used the TIP technique to repair all their included patients. Subgroup analysis in these studies shows no statistical difference among the studied variables (RR=0.69, 95% CI=0.48 to 1.00).

Meatal stenosis

Only three studies included in the meta-analysis reported this outcome. The pooled analysis (figure 2B) of these three studies revealed no discernible difference in the rate of meatal stenosis between the PDS and PG groups, with substantial heterogeneity (p=0.29, RR=0.56, 95% CI=0.29 to 1.08, I²=69%).

Stricture

Only two studies included in the meta-analysis reported this complication. A pooled analysis (figure 2C) of the two studies failed to show a statistical difference in the stricture rate between the PDS and PG groups without heterogeneity (p=0.08, RR=0.34, 95% CI=0.10 to 1.15, I²=0%).

Wound infection

Only three included studies in the meta-analysis reported this complication. Pooled analysis (figure 2D) of the three studies showed no significant difference in the wound infection rate between the PDS and PG groups (p=0.16, RR=0.56, 95% CI=0.25 to 1.27, I²=0%) without heterogeneity.

Total complications

All five studies included in this meta-analysis reported this outcome. The reported incidence of total complications outnumbered the included patients in the study by Fakhr.14 The development of multiple complications in a single patient in this study is a plausible explanation. We analyzed it as per the number of patients who developed the complications; however, we excluded the study from the analysis of this outcome. Khalid et al.9 reported that all patients with wound infection also had UCF, so we calculated the total number of patients with complications excluding this number. Pooled analysis (figure 2E) of the remaining four studies showed no statistically significant difference in the incidence of total complications among the PDS and PG groups (p=0.07, RR=0.57, 95% CI=0.31 to 1.04, I²=77%) with substantial heterogeneity.

Glans dehiscence

This outcome was reported by only one study, so pooled analysis was not done.

Discussion

The present systematic review revealed a decreased incidence of UCF among the pediatric patients in whom PDS was used for the hypospadias repair. The other outcome variables such as meatal stenosis, wound infection, stricture rate, and total complications were comparable in both PDS and PG groups.

Suture choice for hypospadias repair depends on factors like absorption time, tensile strength, and surgeons’ preference based on their experience. Various researchers have debated the ideal absorbable suture material for hypospadias repair. Different suture materials have been studied in vivo and in vitro for their suitability for hypospadias repair. Shirazi et al.19 studied the effect of different types of absorbable suture materials for hypospadias correction in a rat model. They found chromic catgut, poliglecaprone 25, PG 910, and polylactic acid suitable for urethroplasty. In the PDS group, the volume of the urethral epithelium was found to be higher compared with other suture materials. Bartone et al.20 studied chromic catgut, PDS, and polyglycolic acid (Dexon) under similar conditions in the penile foreskin of baboons. They concluded that chromic catgut is the best suture for use in the penile foreskin. Polyglycolic acid and PDS should be avoided in hypospadias repair because of their prolonged resorption and excess tissue reaction.20 A porcine model study on UCF by Edney et al.21 and Lopes et al.22 found that the suture tracks begin to develop from day 5, and a mature fistula is found around day 12. Therefore, the ideal suture material should have a minimum tensile strength of 5 days and degrade by 12 days before the suture tracks are established, but this quality is lacking in PDS. The suture material is also required to hold the wound together until the healing tissue is strong enough to prevent breakdown. The major drawback of all the above studies was that they were conducted in animal models with no histological resemblance to the human urethra.

The effects of human urine on the tensile strengths of 6/0 Vicryl, Vicryl Rapide, PDS, and Monocryl sutures commonly used in hypospadias surgery were investigated by Kerstein et al.23 Vicryl was the best suture for hypospadias repair which balanced the dangers of foreign body reaction with sufficient duration of support for the healing surgical incision. DiSandro and Palmer24 evaluated the stricture incidence in hypospadias surgery using sutures like PDS, chromic catgut, and polyglycolic acid. They found that PDS had a three to four times higher incidence of stricture formation than chromic catgut and polyglycolic acid. They proposed that the best results in hypospadias correction come from sutures with mid-range absorption rates.24 The delayed in vivo absorption rate of PDS should preclude its use in urethral anastomosis.24 Guarino et al.10 compared the results of hypospadias using PG and PDS. They found no statistically significant differences among both sutures regarding the development of UCF. Their long-duration follow-up study detected a greater incidence of pinpoint fistulae in the PDS group. They attributed the prolonged persistence of PDS and subsequent epithelialization of the suture track to fistula formation. However, they concluded that both suture types are suitable for hypospadias surgery.

Though the use of Vicryl seems ideal based on the studies mentioned above, it is a polyfilament suture at risk of inducing severe local inflammation. It also has the highest bacterial adherence compared with other monofilament sutures like Monocryl.25 Wound infection may act as a nidus leading to the development of UCF. Delicate tissue handling, magnification, and tension-free repair are the strategies against fistula prevention. PDS has been used worldwide by many hypospadias surgeons over the years with comparable rates of complications. Ulman et al.11 were the first to compare PDS and PG; they observed that subcuticular PDS sutures were associated with a lower complication rate. This study was excluded from our meta-analysis due to a difference in the suturing technique, which can act as a confounding factor for UCF development as per a recent meta-analysis.26 In our quantitative analysis, there is heterogeneity in suturing technique among the different studies but not among the PDS and PG groups. Almost all studies using animal models had discouraged PDS for hypospadias repair to minimize the incidence of UCF; however, our meta-analysis shows a decreased incidence of UCF with PDS. Our meta-analysis also raises a question about the validity of animal studies for hypospadias repair. A recent publication by Yamashiro et al.27 has discussed the various suture materials in the variability of surgical practice and instrumentation used for hypospadias repair. In their analysis, PG stands as the first choice as suture material among surgeons, followed by PDS, which also substantiates the need for our quantitative analysis on choice of suture material.