Prospective Randomized Comparison of Distal Extension of Midline Urethral plate Incision and Standard Tubularized Incised Plate Urethroplasty – Do Anatomical Penile Measurements Influence the Outcomes?

Background: Since invention of tubularized incised plate urethroplasty, many modifications have been proposed searching for excellence and perfection. Distal extension of the midline urethral plate incision beyond glanular demarcation as a modification of the standard technique was critically evaluated and compared with the original technique in a prospective study and investigating predictors of success. Methods: In this prospective study, patients with primary distal hypospadias presented for repair between June 2015 and January 2019 were randomized to undergo either extended midline incision of the urethral plate (e-TIP) or standard technique (s-TIP). Cosmetic outcome was evaluated postoperatively using Hypospadias Objective Penile Evaluation (HOPE) score and measuring ventral glans closure length (VGCL) and meatal length (ML). The functional outcome was assessed by uroflowmetry and postvoid residual urine. Qmax and Qave values were plotted against voided volume on a nomogram of age matched children. The impact of preoperative parameters on the outcomes were assessed with linear regression analysis. Results: Out of 110 randomized, 94 cases were available for analysis, 46 in e-TIP group and 48 cases in s-TIP group with comparable preoperative demographics. Postoperatively, higher median (range) of HOPE score in e-TIP was 57(45–60) versus 55(44–60) in s-TIP (p <0.001). Mean (SD) ventral glans closure to meatal length ratio was 87% (26) versus 46% (12) in e-TIP vs. s-TIP, respectively (p<0.001). Complications and functional results were insignificantly different between both groups. On linear regression analysis, the urethral plate (UP) width and the use of e-4

TIP technique were significant predictors of better cosmetic outcome (p=0.019 and 0.001, respectively).
Conclusion: The e-TIP ensures creation of a vertical slit-like meatus at the glans tip emulating the normal anatomy with satisfactory functional, and apparently better cosmetic outcomes compared with the s-TIP. Wide urethral plate and the use of e-TIP were significant predictors of higher HOPE score, implying better cosmetic outcome.

Background
Hypospadias is the second most common anomaly in boys after undescended testes [1]. Despite the description of more than 300 surgical techniques for repairing hypospadias, there is no consensus on an optimal technique [2]. In early nineties, Snodgrass introduced the tubularized incised plate (TIP) and since that time it became the preferred choice by most surgeons. In the standard TIP (s-TIP) by Snodgrass, the urethral plate (UP) incision shouldn't extend to the apical part of the glans for fear of meatal stenosis. Therefore, the meatus won't reach the glans tip [3].To improve the cosmetic outcome and bring the meatus at the tip of the penis mimicking the normal position, distal extension of the urethral plate midline incision was described with promising early results regarding the cosmetic and functional outcomes [4]. In the present study, we objectively compared functional and cosmetic outcomes between the extended tabularized incised plate (e-TIP) and standard TIP (s-TIP) techniques and assessed the impact of preoperative penile biometrics on these outcomes.

Methods
The primary outcome (technical success) included a straight penis, an acorn-shaped glans, slit-like meatus located at the tip of the penis and single urinary stream of adequate force and calibre with no complications or need for redo surgery. Cosmetic evaluation done by an independent urological surgeon (KE) using Hypospadias Objective Penile Evaluation (HOPE Score) at least 3 months after surgery [6]. HOPE Score assesses 6 parameters (position of meatus, shape of meatus, shape of glans, shape of penile skin, penile axis including penile torsion and penile curvature).
Scoring ranges from scale of 1 (minimum) to 10 (maximum) for each parameter, giving a minimum total score of 6, up to a maximum total score of 60 when giving the highest score for each variable. Additionally, the proportional relationship between meatal length (ML) and ventral glans closure length (VGCL) was assessed ( Figure 1 f) where normally VGCL and ML are equal or the VGCL is slightly less than meatal length [7].
Functional evaluation: Secondary outcomes were uroflow (using Laborie Dorado™ KT urodynamic device) and ultrasound measured residual urine (PVR), at last clinic visit at least 6 months after repair in uncomplicated toilet-trained boys. Shape of voiding curve, the maximum (Qmax) and average flow rate (Qave) at a voided volume of >50 mL, and voiding time were assessed. Qmax and Qave was then plotted against voided volume on age matched nomogram [8]. Complications were categorized according to modified Clavien classification based on the procedure needed to correct the defect after with the primary surgery [9].
Statistical analysis: The required sample size was computed by G*Power program version 3.1 using a priori analysis with medium effect size convention of 0.3 for ttest. A total sample size of 82 cases was estimated for 80% power, α error probability of 0.05, and 20% dropout rate. To perform the study, 110 patients were statistically adequate. Statistical analysis was performed with SPSS, Version 22.0.
(Released 2013, IBM, Armonk, NY: IBM Corp, USA). Normality of data were tested using Kolmogorov-Smirnov and Shapiro-Wilk test. Categorical data were summarized as numbers and percentages. Comparisons between the e-TIP and s-TIP were done using independent t-test or Mann Whitney-U test. Categorical data were compared using Chi-square test or Fisher's exact test, as appropriate. Multivariate linear regression analysis was done for prediction of total HOPE score at 6 months.
Regression coefficient with 95% CI was calculated for predictors. All p-values were two sided and were considered significant if less than 0.05.

Cosmetic Outcome
Acceptable cosmetic outcome was obtained in both groups. Details of HOPE score are depicted in table 1, where there was significant difference in the total HOPE score in favour of e-TIP, mainly in the items of meatal position and shape.
Regarding the postoperative outcome ( Table 2),, ML was significantly longer in the s-TIP group, while the VGCL was significantly larger in the e-TIP group. The VGCL to ML ratio was significantly larger in e-TIP group, mean (SD) was 87% (26) in e-TIP group versus 46% (12) in s-TIP group. Accordingly, the HOPE score regarding meatal position and shape were significantly higher in e-TIP group.
Prevalence of complications following both techniques was statistically insignificant, yet, after e-TIP, there were 3 cases of meatal stenosis (MS). There were 7 complications in 5 cases in the e-TIP. Second surgical intervention was needed in 4 cases that were managed after 6 months postoperatively, while one case of MS (Clavien grade 3a) was treated with dilatation under local anaesthesia (Table 2).
Functional outcome usinguroflow study was available for 28 uncomplicated toilettrained boys (29.8%), mean (SE) of age was 43.1 (1.5) months and range from 30 to 60 months at a follow-up period of 23.4 (1.4) months and range from 11 to 48 months. Twelve cases (26%) in e-TIP group and 16 cases (33.3%) in s-TIP group.
Functional outcome was comparable between the two groups, detailed data regarding Qmax, Qave, flow time, voided volume, and PVR are depicted in table 2 and (Figure 3 a, b and Figure 4 a, b). Preoperative parameters that thought to impact the total HOPE score (namely TGD, width of UP, and employment of the e-TIP technique) were entered in linear regression analysis for prediction of total HOPE score. It was found that e-TIP is a significant predictor for HOPE score as it leads to increase in total HOPE score by about 2.5 points more than s-TIP, p = 0.001 (Table   3). Additionally, the preoperative width of UP is another significant predictor of high score (p-value 0.019).

Discussion
Hypospadias repair is a challenging reconstructive procedure with different techniques being currently employed aiming to create a functionally and cosmetically normal penis. Re-evaluation of the already settled techniques with objective assessment of outcomes have a major impact on the evolution of new strategies for creation of a penis that looks normal. The present study objectively compared cosmetic and functional outcomes following a modification of the standard TIP technique (s-TIP) that entails extension of midline incision beyond glanular demarcation (e-TIP) and assessed impact of penile biometrics on the outcomes after both techniques.
In this modification (e-TIP), deep UP midline relaxing incision was done started from within the hypospadiac meatus and to be extended distally to the very tip of the glans then the neourethral tabularization was started from distal to proximal in a way allowing fashioning neomeatus of a suitable calibre located at glans tip. This idea was first described by Jayanthi [5] in 2003 and applied for 110 boys (5-60 months) with primary hypospadias and a follow-up reached 3.5 years with no complications except fistula in one patient. The authors incorporated glans cushions (glanular tissue adjacent to urethral plate) during urethroplasty which naturally created a wider urethra and no need for performing deep incision of plate in all cases [5]. Ten years later, other authors adopted the concept of extending the UPmidline incision to the very tip of the glans and incorporate the glans cushions in urethroplasty that were deeply dissected from glans wings with deep midline incision [4]. In that study, the technique was performed on 43 patients with primary distal hypospadias cases and the cosmetic outcome was assessed by the hypospadias objective scoring evaluation (HOSE) and the functional outcome by assessment of Q-max and PVR. The study found that the new modification ensured the fashioning of a vertical slit-like neomeatus located at the tip of the glans, competing with the normal anatomy [4]. In contrast, Snodgrass and colleagues emphasized that the relaxing should be limited to the UP as it may create a "shelf" [10]. The same authors in another study proposed that suturing the plate too far distally may induce meatal stenosis while the neomeatus should have a wide oval configuration by allocating the most distal stitch at the mid-glans level to avoid meatal stenosis [11].
The width of UP is a paramount factor of TIP technique, Holland and Smith found that complications were more prevalent when UP width <8mm. The authors evaluated 48 patients who underwent distal repair, they found 13% stenosis and 55% fistulae when the UP was flat and narrow that was not the situation when the plate was moderately or deeply grooved. The authors concluded that the midline relaxing incision enabled tubularization but did not lead to adequate neourethral calibre when the plate was narrow or flat in order to avoid fistulas or meatal stenosis [12]. Likewise, in a previously mentioned study, the authors found that UP characteristics were significant predictors of success [4]. In contrary, Nguyen and Snodgrass proclaimed that TIP urethroplasty was applicable regardless of initial UP configuration or width when paying attention to technical details leading to achievement of good cosmetic and functional outcomes with few complications [10].
In the present study, the HOPE score, a photograph-based instrument [6], was applied for cosmetic evaluation, the score has good reliability when experienced by 13 paediatric urologists [13]. Cosmetic outcome as presented by mean (SD) total HOPE score was significantly higher in e-TIP group compared to s-TIP group (56.9 In normal children, external urethral meatus anatomy was investigated by Hutton and Babu [7], they examined the proportional relationship between the ventral glans closure length and meatal length in normal children. The authors found that mean (SD) vertical meatal length was 5.4 (1) mm, ventral glans closure was 4.7 (1.2) mm, and mean (SD) ventral glans closure was 88% (22%) of the vertical meatal length. They concluded that position and size of the external meatus are constant in normal boys and VGC is equal to or slightly less than ML [7]. In the present study, mean (SD) VGC to ML was 87%(26) for the e-TIP group while it was 46%(12) for the s-TIP group with statistically significant difference (p value <0.001) that was comparable to normality in the e-TIP group.
Functional outcome following TIP repair using uroflowmetry had been investigated in many studies signifying the importance of long-term follow-up of those boys and the obtained results were quite controversial. While some studies claimed that majority of patients exhibited normal flow pattern [14][15][16], others reported an obstructed flow in a significant proportion of cases [17,18]. In a systematic review addressing the importance of uroflowmetry studies after TIP repair, 11 studies reported obstructive flow in 24.6% of patients (93 / 378) [19].
In the current study, 28 patients were eligible for uroflowmetry, 12 in e-TIP and 16 in s-TIP group. Uroflow data are depicted in table 2. Using a nomogram for age matched children [8], the Qmax was plotted against the voided volume where 4 out of 28 cases (14.3%) had obstructed flow with a Q-max values below the 5 th percentile on the nomogram, two in each group, that is below than previously reported in the literature [19]. Qmax values in most cases were between 25 th and 50 th percentile of the nomogram while Qave values were above the 5 th percentile (Figure 3 a, b).
The obtained functional results in the current study are comparable with the findings of a previously mentioned study using the same technique where uroflow data were available for 26 asymptomatic toilet-trained boys. Qmax and Qave tended to cluster below the 50 th percentile and 4/26 (15.3%) had a Qmax below the 5 th percentile denoting obstructed flow while their Qave was above the 5 th percentile on the same nomogram [4]. In a study performed by Snodgrass, the flow rate was low in only one patient out of 17 patients underwent TIP repair and followed up for 45 months [20]. Eassa et al. assessed the repair of 59 boys with distal hypospadias by s-TIP technique found that the uroflow curve pattern postoperatively was bellshaped in 16 patients, interrupted in eight, slightly flattened in 20 and a plateau in six [21]. The authors used Gaum Nomogram [22] and found that 36 patients were above the 20 th percentile, 9 were below 5 th percentile and 6 were in-between, and there was a significant PVR in 9 patients. Regarding postoperative complications, there was insignificant difference between both groups (p = 0.737).
Linear regression analysis was run to investigate preoperative parameters that thought to impact the total HOPE score. It was found that e-TIP and width of UP were significant predictors for total HOPE score. The e-TIP led to increase in total HOPE score by about 2.5 points more than the s-TIP technique, P = 0.001 (Table 3) and the preoperative width of UP was another significant predictor of high score (pvalue 0.019).
There are some limitations to the present study, the possibility of subjective misinterpretation of HOPE score by study participants, interindividual variations that led to unintentional errors when measuring TGD and UP width and their impact on reliability of measure. Another limitation is the relatively small number of cases available for uroflow study, which could be due to the relatively young age at operation and short period of follow-up as most children were not old enough to perform uroflow, in addition to absent preoperative uroflow data. Nevertheless, this study enjoys important advantages as it is a randomized prospective study used three objective methods for cosmetic and functional assessment of our results.

Conclusion
Extension of midline urethral plate incision ensures creation of a vertical slit-like meatus located at the glans tip comparable to normal anatomy without compromising the functional outcome, but even better cosmetic outcome compared with the standard tubularized incised plate technique. The UP width was a    eTIP.sav Table 1.docx