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Effet de la centralisation dans la chirurgie de l'hypospadias


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Effet de la centralisation dans la chirurgie de l'hypospadias

SANCHEZ, Oliver Lope


L'hypospadias est une malformation congénitale des organes génitaux touchant environ un garçon sur 300. L'étiologie est multifactorielle et n'est que partiellement élucidée. Les formes sévères associent une coudure de verge importante à une localisation proximale du méat urétral sur la face ventrale de la verge, et un prépuce incomplet. Les taux de complications post-opératoires restent significatifs malgré de nombreuses études cherchant à identifier les paramètres influençant le résultat de cette chirurgie. Un nombre croissant de publications montre un effet bénéfique de la centralisation de la prise en charge de certaines malformations congénitales. Un changement radical dans notre service nous a permis de comparer une période où tous les chirurgiens opéraient ces patients avec une période, après 2007, un seul chirurgien s'occupait des interventions et du suivi. Les résultats postopératoires à moyen terme montre une nette diminution du taux de complications indépendamment de la sévérité, et parle en faveur d'une centralisation de la prise en charge de l'hypospadias.

SANCHEZ, Oliver Lope. Effet de la centralisation dans la chirurgie de l'hypospadias. Thèse de doctorat : Univ. Genève, 2018, no. Méd. 10872

DOI : 10.13097/archive-ouverte/unige:104448 URN : urn:nbn:ch:unige-1044485

Available at:


Disclaimer: layout of this document may differ from the published version.


Surgical treatment of hypospadias: advocacy for centralization

O. L. Sanchez1, G. Kampouroglou2, D. S. Courvoisier3, J. Birraux1*

1 University Center of Pediatric Surgery of Western Switzerland Rue Willy-Donzé 6, 1205 Genève


2 1st Department of Pediatric Surgery, Agia Sophia Children's Hospital, Athens Greece

3 Quality of Care Unit, University Hospitals of Geneva Rue Gabrielle-Perret-Gentil 4, 1205 Genève


*Corresponding author:

jacques.birraux@hcuge.ch (JB)




Hypospadias affects around 1 in 300 boys. Despite the high incidence, the rate of complications of this frequently performed repair surgery is still high and there is wide debate over the possible factors contributing to better outcomes. For other congenital malformations, studies have demonstrated that centralization of care offers better results, however little data is published specifically for hypospadias repair.

Methods and Findings

This retrospective single centered study assesses the effect of centralization of care for hypospadias. We compared as primary outcome the reoperation rate for patients at a time when all surgeons were performing hypospadias repair (n= 64, group 1, 01/2000 - 12/2003), with the results following the centralization of care in the hands of one surgeon (n=83, group 2, 01/2008-12/2011).

Patient characteristics, description of initial malformation, surgical technique, surgeon involved, follow-up and complications were recorded. 8 surgeons performed 64 repairs in the first group and the median follow-up was 30.5 months (range 0-144 months). In the second group, 83 repairs were performed by a single surgeon with a median follow-up of 55 months (range 1-96 months).

Severity of hypospadias was similar in both periods.

The reoperation rate was significantly higher in the first group with multiple involved surgeons compared to the centralized approach (62.5% versus 22.9%, p<0.001 ). Decrease in complication rate was adjusted for possible confounding factors such as patient age, severity of hypospadias and penile curvature and remained highly significant when a single surgeon performed the repair (OR 0.24, p<0.0001). The main limitation of this study is that there was no blinding in the appraisal of surgical results in both groups.


This study shows that centralization of care for malformations such as

hypospadias can benefit patients by decreasing the complication and reoperation rates. This could be partially explained by the caseload increase allowing the surgeon to acquire greater experience and adjust management.



Hypospadias is one of the most frequent urologic congenital malformations in boys, and its prevalence seems to be on the rise in western countries [1], with wide regional variations, ranging worldwide from 1/3000 to 1/135 [2]. Most cases require a surgical correction with the objectives of creating a functional penis adequate for sexual intercourse, producing a correct urethral

reconstruction to allow the patient to stand to urinate, and offering satisfactory cosmetic results [3,4]. To achieve these objectives there are countless described techniques divided into three groups: advancement techniques, tubularization techniques, or the use of grafts and flaps [5].

There is a growing body of literature underlining the effect of the surgeon’s experience on the complication rate of hypospadias repair [6–8]. This has been well studied in other fields of pediatric surgery such as results in Kasai

procedure for biliary atresia, with a significant effect on subsequent need for liver transplant [9], or in cleft lip and cleft palate [10,11]. These studies seem to confirm the intuitive idea that a surgeon’s postoperative results with

hypospadias repair improve with experience. This concept is also supported by current international guidelines [12]. However, it is quite exceptional to find the particular set of events needed to demonstrate the actual effect of centralization in a given clinical setting, and, to the best of our knowledge, only one article addressed the issue of centralization for hypospadias repair [13].

Following a sudden change of staff in our pediatric surgery team, we witnessed a radical change in the management policy of our patients presenting with


hypospadias. Before 2007, all staff pediatric surgeons, including trainees,

operated on hypospadias under supervision; since 2007 all cases, with very few exceptions, were operated on and followed up by one single pediatric surgeon trained in pediatric urology (senior author). Knowing the difficulties

encountered when comparing historical groups, we aimed to assess the

reoperation rate before and after this policy change, while controlling as much as possible for variations found in patients and surgery characteristics.

Materials and Methods

Patient inclusion

All children operated for hypospadias and needing an urethroplasty were included.

Patient exclusion

Patients with hypospadias but not needing an urethroplasty and patients with incomplete or inexistent follow-up records were excluded. In group 2, patients operated by other surgeons than the local urologist were also excluded.


After approval from the local ethics committee (CER 12-223R) we filtered the computerized operating room’s records for the two study periods for all operations mentioning hypospadias related procedures, or hypospadias as the diagnosis. These operations were divided into two study periods: Group 1, operated 01/2000-12/2003 and Group 2, operated 01/2008-12/2011. A standard form comprising information on family history, child co-morbidities, preoperative clinical examination, intraoperative findings, techniques used,


surgeons involved, length of hospital stay, and subsequent follow-up, focusing on complications, patient complaints and need for re-operation was filled in.

Preoperative description and severity of hypospadias were mainly found in the operative description. We analyzed all surgery reports, recording severity of hypospadias and the choice of repair technique from the surgeon’s description.

Our current practice is continued follow-up until the end of puberty,

progressively spacing consultations to every 2 to 3 years. Were determined:

1) Patient follow-up: interval between the first operation and the last known outpatient appointment.

2) Individual surgical-free follow-up: reoperation-free interval following each urethroplasty, i.e. interval between the operation and last known outpatient appointment or, if reoperation is needed, interval between the operation and the outpatient appointment when the complication needing reoperation is first mentioned.

Standardization of surgery

In group 1, description of severity was often limited to meatal position.

Furthermore the dissection technique was not standardized. The aim was often to preserve the distal urethra, even when hypoplastic spongiosum was

encountered. In this group, all sutures were 6-0 Polyglyconate Monofilament (MaxonTM – Covidien®). Patients were equipped with indwelling urinary catheters (Vigon® 8-10 Fr). A dressing with Telfa® gauze was kept for 7 to 10 days.

In group 2, surgical techniques and post-operative care were standardized by the single pediatric urologist as follow: All patients received an adjunctive caudal


anesthesia, optical magnification (x3.2) was used for all procedures and bloodless field was maintained during surgery using a penile tourniquet when possible. In cases of penoscrotal or perineal hypospadias with severe curvature, a Koyanagi-Hayashi technique was chosen. In all other cases a standardized dissection was respected for all patients as follows: longitudinal para-urethral incision on both sides of the urethra deepened onto the corpus cavernosum.

These incisions join anteriorly proximally to the hypoplastic urethra. The lateral free edges of the foreskin are then incised. Dissection of the ventral aspect of the penis and degloving of the shaft generally allowed correction of chordee. When in doubt an erection test was performed, and dorsal transverse albuginea plication (TAP) done if needed. At this stage, taking into account the level of the normal urethra with spongiosum covering and the quality of local tissues, the reconstruction technique is decided upon. Urethroplasty is performed using 7-0 polydioxanone (PDSTM – Ethicon®). In this group, all patients are circumcised before performing skin closure. Every patient is post-operatively equipped with an indwelling urinary catheter (Vigon® 8 Fr feeding tubes), secured to the glans, for 5 to 14 days depending on surgical technique, with a daisy-type dressing comprising sulfadiazine and hyaluronate cream and Mepitel® gauze. The

catheter is either connected to a bag in older boys or left to drain in the diaper in younger patients. In both groups, antibiotics and dressing are continued until removal of the catheter, with a change of dressing at day 5. Patients remained on the ward until removal of the catheter and passing urine adequately.

Complication description

We retained a low threshold regarding complication description: all patients


presenting an unsatisfactory postoperative result were considered as having a complication. It should be noted that not all complication required reoperation.

Were considered as complications: stenosis, fistula, partial or complete

dehiscence of urethroplasty, residual curvature or deviation of penile shaft, local infection, residual peno-scrotal web, and, in group 1, dehiscence of preputial reconstruction.

In our practice any significant post-operative painful operative or non-operative procedure needed following a complication in this very young population would entail a general anesthesia. We therefore chose not to use the Clavien-Dindo grading system which would systematically grade all complications as IIIb.

Statistical analysis

To compare patient-related, and surgery-related characteristics between groups, we used Fisher exact test for categorical variables and Wilcoxon rank sum test for continuous variables. To compare incidence of complications between groups, we used Cox regression, accounting for patients being operated by the same surgeon by using a frailty parameter on surgeon. This analysis was

adjusted for the patients’ age, severity of hypospadias and by the curvature of the penis.


Patients’ inclusions, exclusions criteria and characteristics are summarized in Table 1.


Table 1: Inclusion / exclusion criteria and sample characteristics

Group 1 Group 2 p

Number of charts Lost of follow-up

Not needing urethroplasty Bracka 1

Adult Other*

Operated by other surgeons Patients analyzed

85 16 4 0 1 0 N/A N=64

113 5 15 2 0 2 6 N=83

Age in months, mean(SD) 75.2 (85.4) 29.3 (21.6) <0.001

Isolated hypospadias 58 (92.1) 72 (86.7) 0.45

Severity 0.52

Distal or glanular 37 (57.8) 50 (60.2)

Multi-operation 20 (34.4) 20 (24.1)

Proximal 7 (10.9) 13 (15.7)

Surgery **

1) Duplay 42 (65.6) 24 (28.9)

2) Koff 1 (1.6) 2 (2.4)

3) Fistula closure 6 (9.4) 5 (6.0)

4) Secondary tubularisation 2 (3.1) 6 (7.2)

5) Duckett 4 (6.3) 0 (0.0)

6) TIP 8 (12.5) 0 (0.0)

7) Bracka 2 0 (0.0) 3 (3.6)

8) Koyanagi 0 (0.0) 2 (2.4)

9) Matthieu 0 (0.0) 7 (8.4)

10) Bucal mucosa Inlay 0 (0.0) 3 (3.6) 11) Bucal mucosa Onlay 0 (0.0) 1 (1.2)

12) Onlay 0 (0.0) 29 (34.9)

*Exclusion due to complications not linked to urethroplasty: 1 patient with Von Willebrand deficiency; 1 patient suffered extensive burns and unfortunately was equipped with long-term indwelling urethral catheter

** Due to the large number of types of surgery, a p-value could not be reliably computed.

TIP = Tabularized Incised Plate


We hence included 64 hypospadias operations involving an urethroplasty between 01/2000 - 12/2003, and 83 between 01/2008-12/2011. Mean hospital stay was 5.5 days in group 1 and 7.6 days in group 2. Median (range) patient follow up was 30.5 (0-144) months in group 1 and 55 (1-96) months in group 2.

To harmonize description of both groups it was decided to use meatus position to define hypospadias severity, as it was the only available information found systematically for patients in group 1. Overall, in the second period when

operations were centralized, patients were operated at a much younger age. The severity of the hypospadias was similar between periods. In group 1, 8 surgeons were involved in hypospadias surgery. In this group, most proximal and redo hypospadias surgeries were performed by senior surgeons. To note, all surgeons performing more than 5 cases during this period presented a similar

complication rate, around 65%.

Types of complications are described in Table 2. Complications needing reoperation were significantly less frequent in the second period: 22.9 % in group 2 versus 62.5% in group 1 (p<0.001). This decrease was consistent for all severities (Fig 1). Furthermore, it remained highly significant even when

adjusting for possible confounding factors such as: patient’s age, severity of hypospadias and penis curvature (Table 3). When separately analyzing the sub- groups of patients presenting with a complication following the hypospadias repair, we found no statistical difference in reoperation rates: in group 1, 40 patients (95.2%)out of the 42 presenting with a complication and in group 2, 19 out of 21 (86.4%), p=0.86.


Fig 1. Complications. Proportion of complications by severity in both periods

Table 2: Complications

Group 1 Group 2

Fistula 28 (43.7%) 12 (14.5%)

Dehiscence 11 (17.2%) 6 (7.2 %)

Stenosis 3 (4.7%) 0

Residual curvature 5 (7.8%) 2 (2.4%)

Lateral deviation 2 (3.1%) 0

Infection 3 (4.7%) 1(1.2%)

Number of complications 52 in 42 patients 21 in 21 patients Number of patients needing

reoperation 40/64 (62.5%) 19/83 (22.9%)


Table 3: Association of centralization with reoperations

Univariable Adjusted model

OR p-value OR p-value

Period (ref : group 1) 0.24 <0.0001 0.26 <0.0001 Age (in months) 1.00 0.35 1.00 0.91 Severity (ref: distal)

Proximal 1.33 0.45 1.30 0.63

MultiOp 1.42 0.19 1.43 0.16

Curvature (ref: 0)

<20 1.83 0.06 2.04 0.07

20-50 0.84 0.65 1.59 0.40

>50 0.86 0.72 1.49 0.57

Fig 2. Time to reoperation. Kaplan Meier curves of time to reoperation



The aim of this study was to assess the effect of the centralization of care for our hypospadias patients. We acknowledge that there are many controversies regarding management of hypospadias, with great difficulties arising when trying to compare different management modalities, as even basic patient characteristics such as definition of severity of hypospadias are under debate [14,15]. It is widely recognized that enhancing a surgeon’s caseload contributes to increasing his experience and improving outcome. This may seem intuitive, but it remains difficult to demonstrate. The dramatic change in staff and care encountered in our department, allowed us to show that the complications rate decreased very significantly in the second period. This decrease was present for all types of hypospadias, though slightly more pronounced in forms proximal to the mid-shaft, which require complex repairs. Our overall re-operation rate after centralization may seem quite high (23%) but we emphasize that our median follow-up amounts to 55 months. These results are in keep with current

published outcomes: the Ghent team reported a 21.3% reoperation rate for distal hypospadias in 366 patients with a 34 month mean follow-up. This percentage rises to 46% for proximal hypospadias[16]. Interestingly, their Kaplan-Meyer curve of event-free survival is very similar to our own. The team from Lyon reported on long-term follow-up (45.8 months) of 578 Duplay urethroplasties, of which 517 (90%) were done for distal hypospadias. There was 20.4% of

inadequate urethral healing (17.4% specifically for distal hypospadias, vs 18% in group 2 of our study)[17]. To compare our results following centralization with


other reported re-operation rates[16–21], we plotted these published values on our surgical-free time Kaplan-Meyer curve for group 2 (Fig 3).

Fig 3. Reoperation-free time.

There are very few publications on complication rates reported by surgeons infrequently performing hypospadias repair, but the complication rates found in group 1 are similar to the ones described by Hardwicke in an internal audit before a similar strategy change [13]. In group 1, surgeons performed a mean of 2 urethroplasties a year, the most active surgeon performing 5.2 cases per year, as for the surgeon in group 2 this amounted to 20.8 a year which is in keep minimal numbers discussed in current EAU guidelines[12]. To note, senior surgeon in group 2 was one of the surgeons in group 1, showing that further training allows a greater experience to be gathered.[7,22]. Cimador et al.

[23]also point out the importance of an intellectual interest in the field of hypospadiology. In our view, centralizing care in the hands of one surgeon will


allow him to have a greater focus on the specific treated condition, hence better understanding the underlying pathophysiology, following advances in this specific field of surgery and thus adapting his technical approach. We wish to emphasize this last point as we achieve comparable results to high volume centers despite a lower case load. Following these results, we have maintained this policy of centralization allowing a further increase in the annual caseload.

Important issues to address when centralization of care for a specific disease is planned, is continuity of care if a surgeon is unable to work or leaves the

department, and training. We found the improvement of our results has brought an increase in referrals and this additional workload has increased the training possibilities for a single fellow, hence creating a small, specialized team. We also advocate, as a small to middle volume center, long-term cooperation with leading centers. This mentoring has helped maintain knowledge and know-how up to date, discuss strategies, especially for difficult cases and has offered training opportunities for fellows.

As advocated in current literature we offer long-term follow-up after

hypospadias repair, as more than 50% of complications may present after the first year[16]. As recently shown by Cambareri et al.[24], complications appeared continuously for all types of surgical approaches over the observed periods. This is confirmed by our results.

This historical study has several limitations. First, since this study compares two periods in time, the change in complication rate could be due to a cause other than centralization. To address this issue, we only included patients in two 4- year periods separated by a four-year interval, even though the change in patient management occurred over a shorter five-month period. This four-year interval


should help avoid the effects of the transition time, and compare results from steady-state situations. We also verified that equipment and materials used remained similar across periods. Finally, we adjusted for age at surgery and severity of hypospadias. A second limitation concerns information quality regarding patient history and preoperative description in group 1. Lack of standardization is a potential cause of negative impact in surgical outcomes[25]

and made it difficult to institute a systematic approach. We acknowledge the single pediatric urologist active from 2007 established most of the long-term follow-up consultation reports for both groups. Nevertheless, we believe that similar reoperation rate for patients known to have a complication in both groups (95.2% in group 1; 86.4% in group 2, NS), shows that both groups were treated equally by the surgeon on follow-up. Lastly, it would be interesting to measure the parent/patient satisfaction after the procedures for hypospadias repair, and to compare between the two groups. Unfortunately, this was not possible for patients of group 1. To answer this important question, we are currently setting up a cohort study allowing long-term follow-up of patients operated for hypospadias.


Our results offer a strong argument showing that centralization of care for hypospadias improves outcome. This has already been suggested by Horowitz [6] but has also been shown for several other specific pathologies in pediatric surgery such as biliary atresia[9] and cleft lip and palate[10]. A specific focus in the field seems to be of outmost importance, as we achieve these satisfying results despite limited caseloads.



1. Caione P. Prevalence of hypospadias in European countries: is it increasing? Eur Urol. 2009;55: 1027–1030.


2. Li Y, Mao M, Dai L, Li K, Li X, Zhou G, et al. Time trends and geographic variations in the prevalence of hypospadias in China. Birth Defects Res A Clin Mol Teratol. 2011/10/01. 2012;94: 36–41. doi:10.1002/bdra.22854 3. Giannantoni A. Hypospadias classification and repair: the riddle of the

sphinx. Eur Urol. 2011/09/16. 2011;60: 1190–1192. doi:S0302- 2838(11)00975-4 [pii] 10.1016/j.eururo.2011.08.057

4. Tekgül S, Riedmiller H, Dogan HS, Hoebeke P, Kocvara R, Nijman R, et al.

Guidelines on Paediatric Urology - European Society for Paediatric Urology. 2013;

5. Subramaniam R, Spinoit AF, Hoebeke P. Hypospadias repair: an overview of the actual techniques. Semin Plast Surg. 2012/08/02. 2011;25: 206–

212. doi:10.1055/s-0031-1281490

6. Horowitz M, Salzhauer E. The “learning curve” in hypospadias surgery. BJU international. 2006;97: 593–6. doi:10.1111/j.1464-410X.2006.06001.x 7. Chrzan R, Dik P, Klijn AJ, de Jong TP. Quality assessment of hypospadias

repair with emphasis on techniques used and experience of pediatric urologic surgeons. Urology. 2007/07/28. 2007;70: 148–152. doi:S0090- 4295(07)00175-6 [pii]10.1016/j.urology.2007.01.103

8. Lee OT, Durbin-Johnson B, Kurzrock E a. Predictors of secondary surgery after hypospadias repair: a population based analysis of 5,000 patients.


The Journal of urology. Elsevier Inc.; 2013;190: 251–5.


9. Kelly DA, Davenport M. Current management of biliary atresia. Arch Dis Child. 2007/09/20. 2007;92: 1132–1135. doi:adc.2006.101451


10. Fitzsimons KJ, Mukarram S, Copley LP, Deacon SA, van der Meulen JH.

Centralisation of services for children with cleft lip or palate in England: a study of hospital episode statistics. BMC Health Serv Res. 2012/06/12.

2012;12: 148. doi:1472-6963-12-148 [pii]10.1186/1472-6963-12-148 11. Sandy J, Rumsey N, Persson M, Waylen A, Kilpatrick N, Ireland T, et al.

Using service rationalisation to build a research network: lessons from the centralisation of UK services for children with cleft lip and palate. Br Dent J. 2012/06/09. 2012;212: 553–555. doi:sj.bdj.2012.470


12. Tekgul S, Dogan HS, Erdem E, Hoebeke P, Kocvara R, Nijman JM, et al.

Guidelines on Paediatric Urology. European Association of Urology. 2015;

13. Hardwicke J, Clarkson J, Park A. Centralisation of a hypospadias repair service--the Warwickshire experience. J Plast Reconstr Aesthet Surg.

2006/11/28. 2007;60: 61–63. doi:S1748-6815(06)00257-9 [pii]10.1016/j.bjps.2006.02.004

14. Orkiszewski M, Madej J. The meatal/urethral width in healthy uncircumcised boys. J Pediatr Urol. 2009/08/12. 2010;6: 130–133.

doi:S1477-5131(09)00401-X [pii]10.1016/j.jpurol.2009.07.007 15. Snodgrass W, Macedo A, Hoebeke P, Mouriquand PD. Hypospadias

dilemmas: a round table. J Pediatr Urol. 2011/01/18. 2011;7: 145–157.


doi:S1477-5131(10)00518-8 [pii]10.1016/j.jpurol.2010.11.009

16. Spinoit A-F, Poelaert F, Groen L-A, Van Laecke E, Hoebeke P. Hypospadias repair at a tertiary care center: long-term followup is mandatory to

determine the real complication rate. The Journal of urology. Elsevier Inc.;

2013;189: 2276–81. doi:10.1016/j.juro.2012.12.100

17. Grosos C, Bensaid R, Gorduza D-B, Mouriquand P. Is it safe to solely use ventral penile tissues in hypospadias repair? Long-term outcomes of 578 Duplay urethroplasties performed in a single institution over a period of 14 years. Journal of pediatric urology. 2014;10: 1232–7.


18. Snodgrass WT, Bush N, Cost N. Tubularized incised plate hypospadias repair for distal hypospadias. Journal of pediatric urology. 2010;6: 408–13.


19. Pfistermuller KLM, McArdle AJ, Cuckow PM. Meta-analysis of complication rates of the tubularized incised plate (TIP) repair. Journal of pediatric urology. 2015;11: 54–9. doi:10.1016/j.jpurol.2014.12.006

20. Akbiyik F, Tiryaki T, Senel E, Mambet E, Livanelioglu Z, Atayurt H. Clinical experience in hypospadias: results of tubularized incised plate in 496 patients. Urology. 2009;73: 1255–7. doi:10.1016/j.urology.2008.06.075 21. Aslam R, Campbell K, Wharton S, Bracka A. Medium to long term results following single stage Snodgrass hypospadias repair. Journal Of Plastic, Reconstructive & Aesthetic Surgery: JPRAS. 2013;66: 1591–1595.


22. Williams AC, Sandy JR, Thomas S, Sell D, Sterne JA. Influence of surgeon’s experience on speech outcome in cleft lip and palate. Lancet. 1999/11/24.


1999;354: 1697–1698. doi:S0140673699037484 [pii]

23. Cimador M, Vallasciani S, Manzoni G, Rigamonti W, De Grazia E, Castagnetti M. Failed hypospadias in paediatric patients. Nature reviews Urology.

2013;10: 657–66. doi:10.1038/nrurol.2013.164

24. Cambareri GM, Yap M, Kaplan G. Hypospadias Repair with Onlay Preputial Graft: A 25-year experience with long-term follow-up. BJU International.

2016; n/a-n/a. doi:10.1111/bju.13419

25. World Health Organization. WHO Guidelines for Safe Surgery 2009 [Internet]. Who. 2009. Available:



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