Comments on abstract, title, references

The aim of this study is clear, they tested the hypothesis that small glans size could increase urethroplasty complications (UC) following hypospadias repair. The title is informative and relevant, and the references are relevant, recent, and correct. However, the surgical techniques were not clearly stated in the abstract.

Comments on introduction/background

Hypospadias is one of the most common congenital malformations of male external genitalia, of which proximal hypospadias account for 20% of all cases. Despite the evaluation and development of surgical techniques, the complication rate and reoperation rate of hypospadias repair is still far from satisfaction. In authors’ previous study, they speculated that smaller glans size might relate to glans dehiscence postoperatively. In their study, authors hypothesized small glans size could increase UC following hypospadias repair. To test this, they measured glans width at its widest point in consecutive patients with hypospadias, and assessed postoperative UC using pre-determined definitions. They reported analysis of glans size as a potential additional independent risk factor for UC after hypospadias repair. The topic of this article is clear, and the research question is clearly outlined.

Comments on methodology

In this manuscript, the glans width was measured intraoperatively e at its widest point using calipers, after retracting the prepuce and before placing a traction suture. The small glans was defined as width <14 mm (according their previous study). The variables were defined and measured appropriately and the study methods are valid and reliable. The included and excluded criterion were explicit.

The standardized management protocol was performed. TIP (tubularized incised plate) was done for all distal repairs, and for proximal operations when there was ventral curvature <30° after degloving and ventral dartos dissection. Proximal hypospadias cases with >30° curvature had urethral plate transection and a twostage graft procedure using prepuce or oral mucosa, depending on family preference for circumcision or prepucioplasty. Routine follow-up for all patients included assessment at 6 weeks and then 6 months later (8 months postoperatively). Patients with proximal repairs and reoperations had additional evaluations 1 year later, with continuing annual follow-up for those who had proximal hypospadias. The definations of Urethroplasty complications were specific, including fistulas, glans dehiscence, meatal stenosis, urethral strictures and diverticulum. However, recurrent ventral curvature was not included which may due to the insufficient follow-up period.

For statistical analysis, univariate analyses were performed with chi-square or Fisher’s exact testing to compare groups of patients with and without UC, the primary outcome variable, and Spearman’s correlation was used to analyze glans size by patient age. Multivariate logistic regression was used to assess the presence or absence of UC (fistula, glans dehiscence, diverticulum, stricture, and/or meatal stenosis) based on glans size while adjusting for patient age, meatal location (distal or midshaft/proximal), surgeon (WTS/NCB), type of surgery (TIP, inlay, and two-stage), and primary or reoperative repair. Glans size in mm was analyzed in two ways: as a continuous variable or a dichotomous variable (13 mm vs. 14 mm). Stepwise logistic regression was performed. The area under the curve (AUC) for the multiple logistic regression model was reported. In my opinion, for varibles did not follow the normal distribution, univariate analyses should be performed with univariate logistic regression instead of Spearman’s correlation, which may lead the bias.

Comments on data and results

In this section, their results showed that eighty-one (17%) boys had glans width <14 mm. UC occurred in 61 (13%) patients, including 20/81 (25%) patients with small glans <14 mm, versus 41/409 (10%) in patients with glans width 14 mm (p < 0.01). patients with glans width <14 mm compared with those with glans width 14 mm were more likely to have fistulas (11% vs. 5%), glans dehiscence (10% vs. 4%), and meatal stenosis or neourethral strictures (2.5% vs. 1.5%). Univariate analysis also demonstrated that UC were more common in patients with midshaft and proximal hypospadias (27% midshaft/proximal repairs vs. 9% in primary and reoperative distal TIP, p < 0.0001) and in patients undergoing reoperation (29% reoperation vs. 10% primary surgery [distal to perineal], p < 0.0001).

Results of multivariable analysis adjusting for age, meatal location, surgeon, repair type, and reoperation are shown in Table 2. Glans size <14 mm was an independent risk factor for UC (OR 3.5, 95% CI 1.8e6.8). Additional analysis using glans size as a continuous variable demonstrated that each 1 mm decrease in size was associated with increased risk, while conversely each 1 mm increase in size was associated with a decreasing risk for UC (OR 0.77, 95% CI 0.65e0.90, AUC Z 0.696). Midshaft/proximal meatal location and reoperation also increased risk for UC.

Tables relevant and clearly presented and the units, rounding, and the number of decimals is appropriate. However, there are limitations should be noted. First, the baseline detailed in two group are missed, the confounding factors could have introduced bias and possibly influenced the results. Second, authors did not explian why they incorporated age, meatal location, surgeon, repair type, and reoperation into multivariable analysis, whereas suture materials, barrier layers covering the neourethra were not included. Third, as stated in the manuscript, the AUC of glan width was 0.696, but the AUC below table 2 is 0.699, authors should explain it. In order to modify this factor, we encouraged using 1:2 or 1:3 PSM (Propensity Score Matched) method to balance the confounders.

Comments on discussion and conclusions

In this study, their analysis of prospectively collected data from a standardized management protocol in 490 consecutive boys undergoing hypospadias repair adds small glans size, defined as width <14 mm, to proximal meatal location and reoperation as an independent risk factor for UC.

Their study does not explain why a small glans increases UC. It is possible the neourethra is also smaller in patients with glans size <14 mm. We did not calibrate the neourethra to determine its maximum size and so cannot answer that question. However, the prevalence of meatal stenosis <8Fr was only 2.5% of those with the smallest glans, suggesting that even if the caliber of the neourethra is less in these patients, it still is within the normal range of prepubertal boys in the vast majority [3]. Nevertheless, this observation is potentially important for future analyses of hypospadias outcomes.

Furthermore, authors subsequently proposed three methods to increasing the glan size by preoperative androgen therapy, modifying glansplasty, or postponing surgery until puberty when the glans naturally enlarges. However, as they stated, although they successfully increased the small glans from a mean pre-treatment size of 12 mm to a mean of 16.5 mm after preoperative androgen therapy, UC were not decreased. Similarly, waiting for the glans to grow in size may not reduce UC. In other words, although small glans size predicts increased complications, simply increasing the diameter may not improve outcomes. That is a very interesting findings, detailed explanation needs to be further investigated.

In conclusion section, obviously the conclusions answer the aims of the study and it was supported by references. However, glans size in mm was analyzed in two ways: as a continuous variable or a dichotomous variable (<13 mm vs. >14 mm), the results showed that the continuous variable of glan size was an independent risk factor for UC after hypospadias repair, but the dichotomous glan width, as mentioned in the manuscript, might be stimulated by other factors. Thus, I think the conclusion should be modified to smaller glans was an independent risk factor for UC.

Overall

After all, the study design is appropriate to answer the aim and the article is consistent within itself. Their data suggest that others analyzing potential risks for hypospadias UC should similarly measure and report glans width. However, as the authors admitted, better means to modify this factor (such as PSM method) remain to be determined, and some questions needs to be further investigated.

Conflicts of interest

None.