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Age does not impact risk for urethroplasty complications after tubularized incised plate repair of hypospadias in prepubertal boys
Journal of Pediatric Urology (2013) 9, 252e258
REVIEW ARTICLE
Age does not impact risk for urethroplasty complications after tubularized incised plate repair of hypospadias in prepubertal boys Nicol Corbin Bush a,*, Michael Holzer a, Song Zhang b, Warren Snodgrass a a Division of Pediatric Urology, The University of Texas Southwestern Medical Center and, Children’s Medical Center, 2350 Stemmons Freeway Suite F4300, Mail Stop F4.04, Dallas, TX 75207, USA b Department of Clinical Science, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Received 22 October 2011; accepted 23 March 2012 Available online 26 April 2012
KEYWORDS TIP; Hypospadias repair; Age; Anesthetic risk; Complications
Abstract Objective: Patients often present before or after the recommended age of 6e18 months for hypospadias repair. Reports indicate complications may increase when repair is delayed past 6e12 months of age. We questioned if age was an independent risk for urethroplasty complications (UC). Methods: A prospectively maintained database of consecutive patients undergoing tubularized incised plate (TIP) repair was queried for age at surgery, primary or reoperative TIP, meatal location, glansplasty suture, and learning curve. The presence of UC (fistula, dehiscence, stricture, meatal stenosis) was analyzed with logistic regression. Results: TIP repairs were performed for 669 consecutive prepubertal patients aged 3e144 months (mean 17.1, SD 22.5). Original meatal location was distal in 540 (80.7%), midshaft in 50 (7.5%), and proximal in 79 (11.8%). Reoperative TIP occurred in 73 (10.9%). UC occurred in 77 (11.5%). Reoperative TIP (OR 3.07, 95% CI 1.54e6.13) and meatal location (OR 1.79, 95% CI 1.34e2.40) were the only independent risk factors for UC. Neither younger nor older age increased risk for UC. Conclusions: Our data from consecutive TIP repairs in prepubertal children indicate age at surgery does not increase odds of UC. Surgery can be performed any time after 3 months (in full-term, healthy boys) without raising the rate of UC. Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company.
* Corresponding author. Tel.: þ1 214 456 0619; fax: þ1 214 456 8803. E-mail address: [email protected] (N.C. Bush). 1477-5131/$30 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company. http://dx.doi.org/10.1016/j.jpurol.2012.03.014
Age related complications after hypospadias repair
Introduction Timing of hypospadias repair is influenced by penile size, genital awareness, and anesthetic risks. An earlier recommendation that surgery be performed after 3 years of age was revised in 1996 with the current opinion that repair is best done between 6 and 18 months [1]. However, several authors have reported that complication rates increase when surgery is done after age 6 months [2] or 1 year [2e5]. We reviewed our experience in consecutive prepubertal patients undergoing tubularized incised plate (TIP) hypospadias repair to determine if age impacted urethroplasty outcomes.
Materials and methods A database of consecutive patients undergoing hypospadias repair by WS from September 1999 to March 2011 was reviewed with IRB approval. Information concerning patient age at surgery, surgical details, and urethroplasty outcomes was prospectively maintained. We evaluated the following potential risk factors: age at surgery, primary versus reoperative surgery, original meatal location (defined as location of the meatus at the beginning of urethroplasty), glansplasty suture type (chromic versus polyglactin), and learning curve (first 50 cases). Inclusion criteria were successive prepubertal patients with minimum follow-up of 1 month. All patients with distal and midshaft hypospadias were repaired by TIP, as were all patients with proximal hypospadias in whom the urethral plate could be conserved during straightening maneuvers. Reoperations were done by TIP when the urethral plate was available and without gross scarring. Only patients with non-TIP repairs (patients with proximal hypospadias undergoing urethral plate transection to correct ventral curvature > 30 during primary repairs, or those undergoing inlay graft or staged graft repair for reoperations when the urethral plate had been previously excised or was grossly scarred), pubertal patients (Tanner stages 2e5), and those with less than 1 month postoperative follow-up were excluded from analysis. Surgical details of TIP repair have been described previously [6,7]. In all patients, the neourethra was created to achieve an orthotopic meatus within the glans. Glansplasty was independent of the underlying urethroplasty, meaning the glans wings were not sutured to the neourethra. Initially 6-0 chromic was used to approximate glans wings, later changed to 6-0 polyglactin. A 6-Fr urethral stent provided urinary diversion for 7e14 days; less for distal and longer for proximal repairs and reoperations. Tegaderm bandages were used, which fell off spontaneously. All patients were prescribed 4 mg/kg trimethoprim/sulfamethoxazole during stenting, and analgesics. Patients over age 2 years also received 0.2 mg/kg oxybutynin, up to 5 mg, twice daily during stenting. Postoperative follow-up was recommended at 6 weeks and 6 months in all patients with distal and midshaft repair, and yearly thereafter for patients with proximal repairs and reoperations. Urethroplasty complications (UC) were defined as the presence of any one or more of the following at any time during follow-up: fistula, glans dehiscence, urethral stricture and meatal stenosis. Glans dehiscence was diagnosed for complete glans wings separation
253 resulting in a subcoronal meatus. Meatal stenosis was diagnosed when an 8-Fr sound would not traverse the meatus. Urethral stricture was suspected from obstructive symptoms and/or inability to pass an 8-Fr sound 6 months postoperatively, and confirmed by urethroscopy. Additionally, retrospective chart review for all patients aged less than 1 year was performed to identify anesthetic complications, pre-specified as unanticipated overnight hospitalization and/or cardiac arrest.
Measures The primary outcome measure was presence or absence of urethroplasty complications. We modeled the probability for these complications with logistic regression. Potential risk factors (covariates) analyzed included: meatal location (distal, midshaft, or proximal; coded with “distal location” as the reference group), reoperative TIP (coded binomially as yes/no, with “no revision” as the reference group), glansplasty suture type (coded binomially as polyglactin/ chromic, with “polyglactin” arbitrarily assigned as the reference group), and learning curve (first 50 patients undergoing hypospadias repair by WS, coded binomially as yes/no, with “no learning curve” as the reference group). Since age at surgery was the primary risk factor of interest, it was evaluated in several ways. First, age was analyzed as a continuous variable measured in months as well as the log transformation of age in months. We also divided patient ages into quartiles and analyzed the four age group categories: 3e5 months, 6e9 months, 9e17 months, and 17e144 months. Finally, we assessed age group categories as binary risk factors: infants under 6 months versus patients older than 6 months, infants under 12 months versus patients older than 12 months, and patients under 5 years versus those older than 5 years.
Statistical analysis Multiple logistic regression was used to estimate the adjusted odds of urethoplasty complications, initially with all risk factors included in the model. Since age was the primary risk factor of interest, age in months was included in the final model. Stepwise regression was then used to eliminate non-contributory potential risk factors. As a point of reference, the unadjusted odds ratios were also estimated for each risk factor using univariate logistic regression. The 95% confidence intervals (CI) were calculated for the odds ratios (OR), and the likelihood ratio Chi-square statistic was used to test for a significant association between each risk factor and UC. The area under the curve (AUC) for the multiple logistic regression model is reported. Statistical analyses were performed using SAS 9.2 (SAS Institute, Inc., Cary, NC, USA). The level of significance for all tests was set at a Z 0.05 (two-tailed) and p-values were left unadjusted for multiple testing.
Results Primary or reoperative TIP hypospadias repairs were performed on 669 consecutive prepubertal patients (Fig. 1), ranging in age from 3 to 144 months, with a mean/median
254
N.C. Bush et al. required intraoperative treatment for bronchospasm that was documented in the anesthetic record but did not meet our pre-specified criteria for anesthetic complication.
Discussion
Figure 1 Inclusion and exclusion criteria for consecutive patients undergoing repair of hypospadias.
age of 17.1/9.0 months (standard deviation 22.5; interquartile range 12.0). Original meatal location was distal in 540 (80.7%), midshaft in 50 (7.5%), and proximal in 79 (11.8%) patients. Reoperative TIP took place in 73 boys (10.9%). UC occurred in 77 (11.5%) patients, including 36/491 (7.3%) patients with distal, 8/44 (18.2%) with midshaft, 15/ 61 (24.6%) with proximal, and 18/73 (24.7%) with reoperative TIP. Patient characteristics, based on the presence or absence of UC, are shown in Table 1. Complication rates were similar across various age groups, including patients aged less than 6 months at repair, as well as those 5 years and older. UC and patient characteristics by age group are shown in Table 2. Multiple logistic regression (Table 3) demonstrated that reoperative TIP (OR 3.07, 95% CI 1.54e6.13) and meatal location (OR 1.79, 95% CI 1.34e2.40) were the only independent risk factors for UC, with age, log age, quartiles of age, age < 6 months, age > 1 year, age > 5 years, learning curve, and glansplasty suture type all noncontributory to the risk of UC. The AUC of the final model including meatal location, reoperative TIP, and age was 0.652. None of the 223 (33.3%) patients aged less than 12 months experienced an anesthetic complication, which we pre-defined as unexpected overnight hospitalization to account for respiratory issues, and/or cardiac arrest. Five patients, three aged 3e5 months, comprising 1.7% of the 173 patients operated at less than 6 months of age,
Guidelines from both the American Academy of Pediatrics (AAP) and European Association of Urology (EAU) recommend hypospadias surgery between the ages of 6 and 18 months. However, these recommendations were derived from level 4 evidence (expert opinion), and the EAU panel noted evidence obtained from ‘well-designed nonexperimental studies’ (level 3) supported repair as early as 4 months of age [8]. Nonetheless, reports indicate UC increase at varying ages when hypospadias repair is delayed past 6 months [2] or beyond 1 year of age [2e5]. Thus, optimal timing of surgery to minimize surgical complications is of obvious importance to both surgeons and patients. Many factors may influence the timing of hypospadias repair, including age at referral, other health issues impacting anesthesia risks, insurance coverage, and waiting lists, and parents may express concern about the ideal timing of surgery. Our data, which provide evidence that UC do not vary between 3 months and 12 years of age, is thus informative for surgeon and parental decision-making. We found meatal location and reoperative surgery were the only independent risk factors among those we analyzed for UC among 669 prepubertal patients undergoing TIP hypospadias repair. Patients with midshaft hypospadias had a 1.8-fold risk of UC, while those with proximal hypospadias had a 3.6-fold risk compared to those with distal hypospadias undergoing primary surgery. Reoperative repair similarly increased odds 3.1-fold. Given the relative rarity of proximal and reoperative cases and their increased risk for complications, we now refer all these to a single surgeon within our group, and have recently reported a series of technical modifications successfully lowering complications after proximal TIP to a rate similar to distal repairs [7]. Neither younger nor older age was associated with increased risk for UC after adjusting for meatal location. In order to fully evaluate age as a potential risk for UC, we incorporated this factor into our multiple logistic regression
Table 1 Patient demographics and univariate analysis for potential risk factors of urethral complications (UC) following TIP hypospadias repair.
Follow-up in months (SD) Age in months (SD) >5 years >1 year <6 months Meatal location of hypospadias
Distal Midshaft Proximal Learning curve (1st 50 cases, 2 excluded as post-pubertal) Redo TIP repair Vicryl suture
Total, n Z 669
No UC, n Z 592
þ UC, n Z 77
P-value (Fisher’s or c2)
9.0 17.1 43 446 230 540 50 79 48
8.5 17.1 37 400 208 492 41 59 44
17.4 12.6 6 46 22 48 9 20 4
0.002 0.478 0.604 0.171 0.254 <0.0001
(11.9) (22.5) (6.4%) (66.7%) (34.4%) (80.7%) (7.5%) (11.8%) (7.2%)
73 (10.9%) 557 (83.3%)
(11.1) (22.8) (6.3%) (67.6%) (35.1%) (83.1%) (6.9%) (10.0%) (7.4%)
55 (9.3%) 493 (83.3%)
(20.4) (16.2) (7.8%) (59.74%) (28.6%) (62.3%) (11.7%) (26.0%) (5.2%)
18 (23.4%) 64 (83.1%)
0.476 0.0002 0.972
Age related complications after hypospadias repair Table 2
255
Characteristics and UC by age group.
Occurrence of UC Meatal location
Distal Midshaft Proximal
Redo repair Learning curve (1st 50 cases, 2 excluded as post-pubertal)
3e5 months, n Z 173
6e11 months, n Z 250
12 months, n Z 246
22 157 8 8 0 6
27 192 23 35 4 29
35 191 19 36 69 13
(9.6%) (90.8%) (4.6%) (4.6%) (0%) (3.5%)
model in several ways, including as a continuous variable, log transformation, quartiles, and age cut-offs of <6 months, >12 months, and >5 years, yet none approached statistical significance. Age less than 6 months neither increased nor decreased the rate of UC. Additionally, chart review for all patients aged less than 1 year demonstrated no anesthetic complications, pre-specified as unanticipated overnight hospitalization and/or cardiac arrest. At our institution, hypospadias repair is successfully performed in full-term patients aged 3 months and older without increased UC or anesthetic risk. Surgery can be performed at this age because the penis has already subjectively responded to postnatal testosterone, which peaks in the first 2 months of life [9], and does not appreciably enlarge with further delay. We postpone surgery until 50 weeks postgestational age in term boys in order to avoid the need for postoperative admission, preferring instead to perform most repairs on an outpatient basis. Premature boys born at less than 37 gestational weeks are not operated until at least 56 post-gestational weeks from their original due date, in order to avoid overnight hospitalization for apnea monitoring recommended with earlier surgery. Age for repair is also influenced by perceptions of uncooperative behavior and/or postoperative emotional disturbances, leading to recommendations that hypospadias surgery be avoided between the ages of 18 months to 3e4 years [10,11]. While we did not perform psychologic assessments, our data do not show an increased risk for UC when surgery was done during this period. In addition, a recent study of health-related quality of life and psychological adjustment in 6‒17-year-old boys based on hypospadias repair before or after 18 months of age reported no differences related to early versus later surgery [12]. Our study was not designed to determine an ideal age for hypospadias repair, and so we make no specific
Table 3 Multiple logistic regression for UC following TIP hypospadias repair.
Age (months) Redo TIP Meatus (distal, mid, prox)
Odds ratio
P-value
95% confidence interval
0.99 3.07 1.79
0.222 0.0015 <0.0001
0.978e1.005 1.537e6.133 1.335e2.400
(10.8%) (76.8%) (9.2%) (14.0%) (1.6%) (11.6%)
(14.2%) (77.6%) (7.7%) (14.6%) (28.1%) (5.3%)
recommendations. Instead, we only questioned whether age at surgery impacted likelihood of UC and designed our study as such. Unlike previous reports suggesting increasing age increases UC, our study specifically isolated age from other potential risk factors, such as meatal location and reoperation, and in doing so found that age at surgery did not increase the rate of UC. Further strengthening our observations is the fact that our data were prospectively collected from a large series of consecutive patients undergoing the same operative technique by the same surgeon, which allowed us to focus on patient age at repair as a potential risk factor for UC, avoiding the variation in UC which may occur among different surgeons using multiple operative techniques. One limitation is that our analysis excluded pubertal and post-pubertal patients. However, few men present for primary hypospadias repair during or after puberty. Excluding such patients allowed for easier comparison to other studies evaluating infants versus older prepubertal children, and decreased skewing of patient age distribution. Another limitation is that our analysis of anesthetic complications was performed by retrospective chart review, but our endpoints, including unexpected hospital stay that would account for significant pulmonary complications and/or cardiac arrest, were readily available for all patients from the anesthetic record and timing of admission/discharge.
Conclusions Our data in consecutive prepubertal boys undergoing TIP hypospadias repair show age at surgery is not a risk factor for UC. Rather, of the potential factors we analyzed, this risk was determined only by meatal location and reoperative repair. Full-term patients with hypospadias can undergo corrective surgery at any age after 3 months with no difference in urethroplasty outcomes.
Conflict of interest None.
Acknowledgments This project was supported by NIH Grant UL1RR024982. Dr. Bush is supported by NIH Grant KL2RR024983 and a research grant from Coloplast Corporation.
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References [1] American Academy of Pediatrics Section on Urology. Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anesthesia. Pediatrics 1996;97:590. [2] Perlmutter AE, Morabito R, Tarry WF. Impact of patient age on distal hypospadias repair: a surgical perspective. Urology 2006;68:648e51. [3] Korvald C, Stubberud K. High odds for freedom from early complications after tubularized incised-plate urethroplasty in 1-year-old versus 5-year-old boys. J Pediatr Urol 2008;4:452e6. [4] Dodson JL, Baird AD, Baker LA, Docimo SG, Mathews RI. Outcomes of delayed hypospadias repair: implications for decision making. J Urol 2007;17:278e81. [5] Ziada A, Hamza A, Abdel-Rassoul M, Habib E, Mohamed A, Daw M. Outcomes of hypospadias repair in older children: a prospective study. J Urol 2011;185(6 Suppl):2483e5. [6] Snodgrass WT, Bush N, Cost N. Tubularized incised plate hypospadias repair for distal hypospadias. J Pediatr Urol 2010;6:408e13.
M. Orkiszewski [7] Snodgrass WT, Bush N. Tubularized incised plate proximal hypospadias repair: continued evolution and extended applications. J Pediatr Urol 2011;7:2e9. [8] Tekgu ¨l S, Riedmiller H, Dogan HS, Gerharz E, Hoebeke P, Kocvara R, et al. Guidelines on paediatric urology. Eur Assoc Urol [accessed March 8, 2012], http://www.uroweb.org/gls/ pdf/21_Paediatric_Urology.pdf; 2012. [9] Quigley CA. Editorial: the postnatal gonadotropin and sex steroid surgedinsights from the androgen insensitivity syndrome. J Clin Endocrinol Metab 2002;87:24e8. [10] Manzoni G, Bracka A, Palminteri E, Marrocco G. Hypospadias surgery: when, what and by whom? BJU Int 2004;94: 1188e95. [11] Vernon D, Foley JM, Schulman JL. Effect of mother-child separation and birth order on young children’s responses to two potentially stressful experiences. J Pers Soc Psychol 1976;5: 162e74. [12] Weber DM, Scho ¨nbucher VB, Gobet R, Gerber A, Landolt MA. Is there an ideal age for hypospadias repair? A pilot study. J Pediatr 2009;5:345e50.
Commentary to ‘Age does not impact risk for urethroplasty complications after tubularized incised plate repair of hypospadias in prepubertal boys’ Marek Orkiszewski * , Jagiellonska 13, Bydgoszcz, Poland Collegium Medicum, Nicolaus Copernicus University, Torun
When I see the title of this paper, I understand three distinctive elements: age, complications, and hypospadias repair. We have adopted the AAP guidelines concerning hypospadias repair, which say that from the viewpoint of emotional development the best time for surgery is as early as 6 months, with the individual surgeon’s skills having the greatest bearing on timing. By surgeon’s skills we usually understand surgeon’s preference. It is not clear what was so important to motivate the authors to operate earlier, and how they explained to parents that the age 3e6 months is better than 6e12, except for, perhaps, the individual surgeon’s skills/preference. An operation on a 3e6-month-old child should, at least theoretically, differ from an operation performed at 6e12 months. The differences might include optical magnification, suture material, type of urethral anastomosis, antibiotics, stenting, to be followed by anatomical details of the procedure: genuine urethral plate only, or, as in most TIP repairs, with the adjacent skin to create a urethral tube of adequate diameter. How about a flat or missing grove, where there is no urethral plate at all? All this information, naturally expected by a reader, is missing. It is a common feeling and experience that operations at 6e12 months of age result in fewer complications than in older age groups, not to mention emotional disturbances. Because the most experienced hypospadiologists have reached a complication rate near zero, especially in the youngest patients, still earlier operations should then offer new and well documented benefits for the patient in the long
term. It is likely that such papers as the recent report on cytokine production by Bermudez et al. will better show and convince us when and also what to repair in hypospadias [1]. The authors mention that the timing of hypospadias surgery is influenced by penile size, and that in patients aged 3e6 months the penis has already subjectively responded to postnatal testosterone, which peaks in the first 2 months of life. This argument appears to be only vaguely consistent with the results of an extensive study by the Scandinavian group, who found that in an exclusively Nordic population penile length according to age showed a curvilinear relationship, with a rapid increase during the first 3 months of life, but penile length was at all ages significantly and positively correlated to body length [2]. Why then should the growth of the normal penis be stimulated? The only medically justified grounds could be a smaller for age penis, which requires early stimulation to make it reach normal length. Good early results confined only to the urethra might have been a success some 30 years ago. Thus, if the authors intend to look at their experience in a wider perspective, they should include late results which to some of us come as a nightmare: penile curvature, late fistulas, and strictures requiring regular dilatations. Repair of these appears to be far more difficult and emotionally severe for both the surgeon and the now adult patient. The authors say that their learning curve was confined to the first 50 patients out of 669 with minor additions thereafter. Since its first description in 1987 [3,4] the TIP procedure has undergone numerous and constant
DOI of original article: http://dx.doi.org/10.1016/j.jpurol.2012.03.014.
REVIEW ARTICLE
Age does not impact risk for urethroplasty complications after tubularized incised plate repair of hypospadias in prepubertal boys Nicol Corbin Bush a,*, Michael Holzer a, Song Zhang b, Warren Snodgrass a a Division of Pediatric Urology, The University of Texas Southwestern Medical Center and, Children’s Medical Center, 2350 Stemmons Freeway Suite F4300, Mail Stop F4.04, Dallas, TX 75207, USA b Department of Clinical Science, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Received 22 October 2011; accepted 23 March 2012 Available online 26 April 2012
KEYWORDS TIP; Hypospadias repair; Age; Anesthetic risk; Complications
Abstract Objective: Patients often present before or after the recommended age of 6e18 months for hypospadias repair. Reports indicate complications may increase when repair is delayed past 6e12 months of age. We questioned if age was an independent risk for urethroplasty complications (UC). Methods: A prospectively maintained database of consecutive patients undergoing tubularized incised plate (TIP) repair was queried for age at surgery, primary or reoperative TIP, meatal location, glansplasty suture, and learning curve. The presence of UC (fistula, dehiscence, stricture, meatal stenosis) was analyzed with logistic regression. Results: TIP repairs were performed for 669 consecutive prepubertal patients aged 3e144 months (mean 17.1, SD 22.5). Original meatal location was distal in 540 (80.7%), midshaft in 50 (7.5%), and proximal in 79 (11.8%). Reoperative TIP occurred in 73 (10.9%). UC occurred in 77 (11.5%). Reoperative TIP (OR 3.07, 95% CI 1.54e6.13) and meatal location (OR 1.79, 95% CI 1.34e2.40) were the only independent risk factors for UC. Neither younger nor older age increased risk for UC. Conclusions: Our data from consecutive TIP repairs in prepubertal children indicate age at surgery does not increase odds of UC. Surgery can be performed any time after 3 months (in full-term, healthy boys) without raising the rate of UC. Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company.
* Corresponding author. Tel.: þ1 214 456 0619; fax: þ1 214 456 8803. E-mail address: [email protected] (N.C. Bush). 1477-5131/$30 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company. http://dx.doi.org/10.1016/j.jpurol.2012.03.014
Age related complications after hypospadias repair
Introduction Timing of hypospadias repair is influenced by penile size, genital awareness, and anesthetic risks. An earlier recommendation that surgery be performed after 3 years of age was revised in 1996 with the current opinion that repair is best done between 6 and 18 months [1]. However, several authors have reported that complication rates increase when surgery is done after age 6 months [2] or 1 year [2e5]. We reviewed our experience in consecutive prepubertal patients undergoing tubularized incised plate (TIP) hypospadias repair to determine if age impacted urethroplasty outcomes.
Materials and methods A database of consecutive patients undergoing hypospadias repair by WS from September 1999 to March 2011 was reviewed with IRB approval. Information concerning patient age at surgery, surgical details, and urethroplasty outcomes was prospectively maintained. We evaluated the following potential risk factors: age at surgery, primary versus reoperative surgery, original meatal location (defined as location of the meatus at the beginning of urethroplasty), glansplasty suture type (chromic versus polyglactin), and learning curve (first 50 cases). Inclusion criteria were successive prepubertal patients with minimum follow-up of 1 month. All patients with distal and midshaft hypospadias were repaired by TIP, as were all patients with proximal hypospadias in whom the urethral plate could be conserved during straightening maneuvers. Reoperations were done by TIP when the urethral plate was available and without gross scarring. Only patients with non-TIP repairs (patients with proximal hypospadias undergoing urethral plate transection to correct ventral curvature > 30 during primary repairs, or those undergoing inlay graft or staged graft repair for reoperations when the urethral plate had been previously excised or was grossly scarred), pubertal patients (Tanner stages 2e5), and those with less than 1 month postoperative follow-up were excluded from analysis. Surgical details of TIP repair have been described previously [6,7]. In all patients, the neourethra was created to achieve an orthotopic meatus within the glans. Glansplasty was independent of the underlying urethroplasty, meaning the glans wings were not sutured to the neourethra. Initially 6-0 chromic was used to approximate glans wings, later changed to 6-0 polyglactin. A 6-Fr urethral stent provided urinary diversion for 7e14 days; less for distal and longer for proximal repairs and reoperations. Tegaderm bandages were used, which fell off spontaneously. All patients were prescribed 4 mg/kg trimethoprim/sulfamethoxazole during stenting, and analgesics. Patients over age 2 years also received 0.2 mg/kg oxybutynin, up to 5 mg, twice daily during stenting. Postoperative follow-up was recommended at 6 weeks and 6 months in all patients with distal and midshaft repair, and yearly thereafter for patients with proximal repairs and reoperations. Urethroplasty complications (UC) were defined as the presence of any one or more of the following at any time during follow-up: fistula, glans dehiscence, urethral stricture and meatal stenosis. Glans dehiscence was diagnosed for complete glans wings separation
253 resulting in a subcoronal meatus. Meatal stenosis was diagnosed when an 8-Fr sound would not traverse the meatus. Urethral stricture was suspected from obstructive symptoms and/or inability to pass an 8-Fr sound 6 months postoperatively, and confirmed by urethroscopy. Additionally, retrospective chart review for all patients aged less than 1 year was performed to identify anesthetic complications, pre-specified as unanticipated overnight hospitalization and/or cardiac arrest.
Measures The primary outcome measure was presence or absence of urethroplasty complications. We modeled the probability for these complications with logistic regression. Potential risk factors (covariates) analyzed included: meatal location (distal, midshaft, or proximal; coded with “distal location” as the reference group), reoperative TIP (coded binomially as yes/no, with “no revision” as the reference group), glansplasty suture type (coded binomially as polyglactin/ chromic, with “polyglactin” arbitrarily assigned as the reference group), and learning curve (first 50 patients undergoing hypospadias repair by WS, coded binomially as yes/no, with “no learning curve” as the reference group). Since age at surgery was the primary risk factor of interest, it was evaluated in several ways. First, age was analyzed as a continuous variable measured in months as well as the log transformation of age in months. We also divided patient ages into quartiles and analyzed the four age group categories: 3e5 months, 6e9 months, 9e17 months, and 17e144 months. Finally, we assessed age group categories as binary risk factors: infants under 6 months versus patients older than 6 months, infants under 12 months versus patients older than 12 months, and patients under 5 years versus those older than 5 years.
Statistical analysis Multiple logistic regression was used to estimate the adjusted odds of urethoplasty complications, initially with all risk factors included in the model. Since age was the primary risk factor of interest, age in months was included in the final model. Stepwise regression was then used to eliminate non-contributory potential risk factors. As a point of reference, the unadjusted odds ratios were also estimated for each risk factor using univariate logistic regression. The 95% confidence intervals (CI) were calculated for the odds ratios (OR), and the likelihood ratio Chi-square statistic was used to test for a significant association between each risk factor and UC. The area under the curve (AUC) for the multiple logistic regression model is reported. Statistical analyses were performed using SAS 9.2 (SAS Institute, Inc., Cary, NC, USA). The level of significance for all tests was set at a Z 0.05 (two-tailed) and p-values were left unadjusted for multiple testing.
Results Primary or reoperative TIP hypospadias repairs were performed on 669 consecutive prepubertal patients (Fig. 1), ranging in age from 3 to 144 months, with a mean/median
254
N.C. Bush et al. required intraoperative treatment for bronchospasm that was documented in the anesthetic record but did not meet our pre-specified criteria for anesthetic complication.
Discussion
Figure 1 Inclusion and exclusion criteria for consecutive patients undergoing repair of hypospadias.
age of 17.1/9.0 months (standard deviation 22.5; interquartile range 12.0). Original meatal location was distal in 540 (80.7%), midshaft in 50 (7.5%), and proximal in 79 (11.8%) patients. Reoperative TIP took place in 73 boys (10.9%). UC occurred in 77 (11.5%) patients, including 36/491 (7.3%) patients with distal, 8/44 (18.2%) with midshaft, 15/ 61 (24.6%) with proximal, and 18/73 (24.7%) with reoperative TIP. Patient characteristics, based on the presence or absence of UC, are shown in Table 1. Complication rates were similar across various age groups, including patients aged less than 6 months at repair, as well as those 5 years and older. UC and patient characteristics by age group are shown in Table 2. Multiple logistic regression (Table 3) demonstrated that reoperative TIP (OR 3.07, 95% CI 1.54e6.13) and meatal location (OR 1.79, 95% CI 1.34e2.40) were the only independent risk factors for UC, with age, log age, quartiles of age, age < 6 months, age > 1 year, age > 5 years, learning curve, and glansplasty suture type all noncontributory to the risk of UC. The AUC of the final model including meatal location, reoperative TIP, and age was 0.652. None of the 223 (33.3%) patients aged less than 12 months experienced an anesthetic complication, which we pre-defined as unexpected overnight hospitalization to account for respiratory issues, and/or cardiac arrest. Five patients, three aged 3e5 months, comprising 1.7% of the 173 patients operated at less than 6 months of age,
Guidelines from both the American Academy of Pediatrics (AAP) and European Association of Urology (EAU) recommend hypospadias surgery between the ages of 6 and 18 months. However, these recommendations were derived from level 4 evidence (expert opinion), and the EAU panel noted evidence obtained from ‘well-designed nonexperimental studies’ (level 3) supported repair as early as 4 months of age [8]. Nonetheless, reports indicate UC increase at varying ages when hypospadias repair is delayed past 6 months [2] or beyond 1 year of age [2e5]. Thus, optimal timing of surgery to minimize surgical complications is of obvious importance to both surgeons and patients. Many factors may influence the timing of hypospadias repair, including age at referral, other health issues impacting anesthesia risks, insurance coverage, and waiting lists, and parents may express concern about the ideal timing of surgery. Our data, which provide evidence that UC do not vary between 3 months and 12 years of age, is thus informative for surgeon and parental decision-making. We found meatal location and reoperative surgery were the only independent risk factors among those we analyzed for UC among 669 prepubertal patients undergoing TIP hypospadias repair. Patients with midshaft hypospadias had a 1.8-fold risk of UC, while those with proximal hypospadias had a 3.6-fold risk compared to those with distal hypospadias undergoing primary surgery. Reoperative repair similarly increased odds 3.1-fold. Given the relative rarity of proximal and reoperative cases and their increased risk for complications, we now refer all these to a single surgeon within our group, and have recently reported a series of technical modifications successfully lowering complications after proximal TIP to a rate similar to distal repairs [7]. Neither younger nor older age was associated with increased risk for UC after adjusting for meatal location. In order to fully evaluate age as a potential risk for UC, we incorporated this factor into our multiple logistic regression
Table 1 Patient demographics and univariate analysis for potential risk factors of urethral complications (UC) following TIP hypospadias repair.
Follow-up in months (SD) Age in months (SD) >5 years >1 year <6 months Meatal location of hypospadias
Distal Midshaft Proximal Learning curve (1st 50 cases, 2 excluded as post-pubertal) Redo TIP repair Vicryl suture
Total, n Z 669
No UC, n Z 592
þ UC, n Z 77
P-value (Fisher’s or c2)
9.0 17.1 43 446 230 540 50 79 48
8.5 17.1 37 400 208 492 41 59 44
17.4 12.6 6 46 22 48 9 20 4
0.002 0.478 0.604 0.171 0.254 <0.0001
(11.9) (22.5) (6.4%) (66.7%) (34.4%) (80.7%) (7.5%) (11.8%) (7.2%)
73 (10.9%) 557 (83.3%)
(11.1) (22.8) (6.3%) (67.6%) (35.1%) (83.1%) (6.9%) (10.0%) (7.4%)
55 (9.3%) 493 (83.3%)
(20.4) (16.2) (7.8%) (59.74%) (28.6%) (62.3%) (11.7%) (26.0%) (5.2%)
18 (23.4%) 64 (83.1%)
0.476 0.0002 0.972
Age related complications after hypospadias repair Table 2
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Characteristics and UC by age group.
Occurrence of UC Meatal location
Distal Midshaft Proximal
Redo repair Learning curve (1st 50 cases, 2 excluded as post-pubertal)
3e5 months, n Z 173
6e11 months, n Z 250
12 months, n Z 246
22 157 8 8 0 6
27 192 23 35 4 29
35 191 19 36 69 13
(9.6%) (90.8%) (4.6%) (4.6%) (0%) (3.5%)
model in several ways, including as a continuous variable, log transformation, quartiles, and age cut-offs of <6 months, >12 months, and >5 years, yet none approached statistical significance. Age less than 6 months neither increased nor decreased the rate of UC. Additionally, chart review for all patients aged less than 1 year demonstrated no anesthetic complications, pre-specified as unanticipated overnight hospitalization and/or cardiac arrest. At our institution, hypospadias repair is successfully performed in full-term patients aged 3 months and older without increased UC or anesthetic risk. Surgery can be performed at this age because the penis has already subjectively responded to postnatal testosterone, which peaks in the first 2 months of life [9], and does not appreciably enlarge with further delay. We postpone surgery until 50 weeks postgestational age in term boys in order to avoid the need for postoperative admission, preferring instead to perform most repairs on an outpatient basis. Premature boys born at less than 37 gestational weeks are not operated until at least 56 post-gestational weeks from their original due date, in order to avoid overnight hospitalization for apnea monitoring recommended with earlier surgery. Age for repair is also influenced by perceptions of uncooperative behavior and/or postoperative emotional disturbances, leading to recommendations that hypospadias surgery be avoided between the ages of 18 months to 3e4 years [10,11]. While we did not perform psychologic assessments, our data do not show an increased risk for UC when surgery was done during this period. In addition, a recent study of health-related quality of life and psychological adjustment in 6‒17-year-old boys based on hypospadias repair before or after 18 months of age reported no differences related to early versus later surgery [12]. Our study was not designed to determine an ideal age for hypospadias repair, and so we make no specific
Table 3 Multiple logistic regression for UC following TIP hypospadias repair.
Age (months) Redo TIP Meatus (distal, mid, prox)
Odds ratio
P-value
95% confidence interval
0.99 3.07 1.79
0.222 0.0015 <0.0001
0.978e1.005 1.537e6.133 1.335e2.400
(10.8%) (76.8%) (9.2%) (14.0%) (1.6%) (11.6%)
(14.2%) (77.6%) (7.7%) (14.6%) (28.1%) (5.3%)
recommendations. Instead, we only questioned whether age at surgery impacted likelihood of UC and designed our study as such. Unlike previous reports suggesting increasing age increases UC, our study specifically isolated age from other potential risk factors, such as meatal location and reoperation, and in doing so found that age at surgery did not increase the rate of UC. Further strengthening our observations is the fact that our data were prospectively collected from a large series of consecutive patients undergoing the same operative technique by the same surgeon, which allowed us to focus on patient age at repair as a potential risk factor for UC, avoiding the variation in UC which may occur among different surgeons using multiple operative techniques. One limitation is that our analysis excluded pubertal and post-pubertal patients. However, few men present for primary hypospadias repair during or after puberty. Excluding such patients allowed for easier comparison to other studies evaluating infants versus older prepubertal children, and decreased skewing of patient age distribution. Another limitation is that our analysis of anesthetic complications was performed by retrospective chart review, but our endpoints, including unexpected hospital stay that would account for significant pulmonary complications and/or cardiac arrest, were readily available for all patients from the anesthetic record and timing of admission/discharge.
Conclusions Our data in consecutive prepubertal boys undergoing TIP hypospadias repair show age at surgery is not a risk factor for UC. Rather, of the potential factors we analyzed, this risk was determined only by meatal location and reoperative repair. Full-term patients with hypospadias can undergo corrective surgery at any age after 3 months with no difference in urethroplasty outcomes.
Conflict of interest None.
Acknowledgments This project was supported by NIH Grant UL1RR024982. Dr. Bush is supported by NIH Grant KL2RR024983 and a research grant from Coloplast Corporation.
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References [1] American Academy of Pediatrics Section on Urology. Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anesthesia. Pediatrics 1996;97:590. [2] Perlmutter AE, Morabito R, Tarry WF. Impact of patient age on distal hypospadias repair: a surgical perspective. Urology 2006;68:648e51. [3] Korvald C, Stubberud K. High odds for freedom from early complications after tubularized incised-plate urethroplasty in 1-year-old versus 5-year-old boys. J Pediatr Urol 2008;4:452e6. [4] Dodson JL, Baird AD, Baker LA, Docimo SG, Mathews RI. Outcomes of delayed hypospadias repair: implications for decision making. J Urol 2007;17:278e81. [5] Ziada A, Hamza A, Abdel-Rassoul M, Habib E, Mohamed A, Daw M. Outcomes of hypospadias repair in older children: a prospective study. J Urol 2011;185(6 Suppl):2483e5. [6] Snodgrass WT, Bush N, Cost N. Tubularized incised plate hypospadias repair for distal hypospadias. J Pediatr Urol 2010;6:408e13.
M. Orkiszewski [7] Snodgrass WT, Bush N. Tubularized incised plate proximal hypospadias repair: continued evolution and extended applications. J Pediatr Urol 2011;7:2e9. [8] Tekgu ¨l S, Riedmiller H, Dogan HS, Gerharz E, Hoebeke P, Kocvara R, et al. Guidelines on paediatric urology. Eur Assoc Urol [accessed March 8, 2012], http://www.uroweb.org/gls/ pdf/21_Paediatric_Urology.pdf; 2012. [9] Quigley CA. Editorial: the postnatal gonadotropin and sex steroid surgedinsights from the androgen insensitivity syndrome. J Clin Endocrinol Metab 2002;87:24e8. [10] Manzoni G, Bracka A, Palminteri E, Marrocco G. Hypospadias surgery: when, what and by whom? BJU Int 2004;94: 1188e95. [11] Vernon D, Foley JM, Schulman JL. Effect of mother-child separation and birth order on young children’s responses to two potentially stressful experiences. J Pers Soc Psychol 1976;5: 162e74. [12] Weber DM, Scho ¨nbucher VB, Gobet R, Gerber A, Landolt MA. Is there an ideal age for hypospadias repair? A pilot study. J Pediatr 2009;5:345e50.
Commentary to ‘Age does not impact risk for urethroplasty complications after tubularized incised plate repair of hypospadias in prepubertal boys’ Marek Orkiszewski * , Jagiellonska 13, Bydgoszcz, Poland Collegium Medicum, Nicolaus Copernicus University, Torun
When I see the title of this paper, I understand three distinctive elements: age, complications, and hypospadias repair. We have adopted the AAP guidelines concerning hypospadias repair, which say that from the viewpoint of emotional development the best time for surgery is as early as 6 months, with the individual surgeon’s skills having the greatest bearing on timing. By surgeon’s skills we usually understand surgeon’s preference. It is not clear what was so important to motivate the authors to operate earlier, and how they explained to parents that the age 3e6 months is better than 6e12, except for, perhaps, the individual surgeon’s skills/preference. An operation on a 3e6-month-old child should, at least theoretically, differ from an operation performed at 6e12 months. The differences might include optical magnification, suture material, type of urethral anastomosis, antibiotics, stenting, to be followed by anatomical details of the procedure: genuine urethral plate only, or, as in most TIP repairs, with the adjacent skin to create a urethral tube of adequate diameter. How about a flat or missing grove, where there is no urethral plate at all? All this information, naturally expected by a reader, is missing. It is a common feeling and experience that operations at 6e12 months of age result in fewer complications than in older age groups, not to mention emotional disturbances. Because the most experienced hypospadiologists have reached a complication rate near zero, especially in the youngest patients, still earlier operations should then offer new and well documented benefits for the patient in the long
term. It is likely that such papers as the recent report on cytokine production by Bermudez et al. will better show and convince us when and also what to repair in hypospadias [1]. The authors mention that the timing of hypospadias surgery is influenced by penile size, and that in patients aged 3e6 months the penis has already subjectively responded to postnatal testosterone, which peaks in the first 2 months of life. This argument appears to be only vaguely consistent with the results of an extensive study by the Scandinavian group, who found that in an exclusively Nordic population penile length according to age showed a curvilinear relationship, with a rapid increase during the first 3 months of life, but penile length was at all ages significantly and positively correlated to body length [2]. Why then should the growth of the normal penis be stimulated? The only medically justified grounds could be a smaller for age penis, which requires early stimulation to make it reach normal length. Good early results confined only to the urethra might have been a success some 30 years ago. Thus, if the authors intend to look at their experience in a wider perspective, they should include late results which to some of us come as a nightmare: penile curvature, late fistulas, and strictures requiring regular dilatations. Repair of these appears to be far more difficult and emotionally severe for both the surgeon and the now adult patient. The authors say that their learning curve was confined to the first 50 patients out of 669 with minor additions thereafter. Since its first description in 1987 [3,4] the TIP procedure has undergone numerous and constant
DOI of original article: http://dx.doi.org/10.1016/j.jpurol.2012.03.014.