Paediatric Urology

9. HYPOSPADIAS

9.1. Epidemiology, aetiology, and pathophysiology

9.1.1. Epidemiology

The total prevalence of hypospadias in Europe is 18.6 new cases per 10,000 male births (5.1-36.8) according to the EUROCAT registry-based study [335]. Worldwide, there is variation in the prevalence of hypospadias according to an extended systematic literature review: Europe 19.9 (range: 1-464), North America 34.2 (6-129.8), South America 5.2 (2.8-110), Asia 0.6-69, Africa 5.9 (1.9-110), and Australia 17.1-34.8 per 10,000 [336].

9.2. Risk factors

Risk factors associated with hypospadias are likely to be genetic, placental and/or environmental [337-339]. Interactions between genetic and environmental factors (endocrine-disrupting chemicals) may help explain nonreplication in genetic studies of hypospadias [340,341].

The following risks factors has been associated with hypospadias:

• An additional family member with hypospadias is found in 7%-12.9% of families and is more predominant in anterior and middle forms [342,343].
• Infants with low birth weight or being small for gestational age (SGA) have a higher risk of hypospadias [342]. Furthermore, SGA might also be associated with a higher reoperation rate in proximal hypospadias [337,343,344].
• Maternal hypertension during pregnancy and preeclampsia has been shown to be associated with hypospadias, likely due to that both factors may be associated with placental dysfunction [337].
• Pregestational diabetes mellitus and gestational diabetes mellitus are associated with an increased risk of hypospadias in offspring [345].

9.3. Classification systems

Hypospadias is usually classified based on the anatomical location of the proximally displaced urethral orifice [346]:

• distal-anterior hypospadias (located on the glans or distal shaft of the penis);
• intermediate-middle (penile); and
• proximal-posterior (penoscrotal, scrotal, perineal).

The pathology may be different after skin release and should be reclassified accordingly [347]. The anatomical location of the meatus may not always be enough to explain the severity and the complex nature of this pathology. When evaluating the severity of the hypospadias, the consensus of the Panel is to consider factors such as penile length, penile curvature, glans size and shape, and urethral plate quality.

9.4. Diagnostic evaluation

Most hypospadias patients are easily diagnosed at birth (except for the megameatus intact prepuce variant, which can only be seen after retraction of foreskin). Diagnosis includes a description of the local findings:

• position, shape and width of the meatal orifice;
• presence of atretic urethra and division of corpus spongiosum;
• appearance of the preputial hood and scrotum;
• size of the penis; and
• curvature of the penis on erection.

The diagnostic evaluation also includes an assessment of associated anomalies, which are:

• congenital cryptorchidism (2%-6.2%) [348,349]
• acquired undescended testes (1%-14%) [348-350]

In hypospadias patients with bilaterally undescended testis, complete genetic and endocrine workup soon after birth to exclude DSD, particularly congenital adrenal hyperplasia [66]. Urine trickling and ballooning of the urethra requires exclusion of meatal stenosis. There are conflicting data on presence of additional birth defects in urogenital system (e.g. UPJ stenosis, renal agenesis and dysgenesis, cystic kidney disease) in hypospadias patients with unrecognised syndromes. The Panel consensus it not to perform imaging studies in hypospadias patients.

9.5. Management

The natural history of untreated hypospadias is poorly documented. Studies of adult men with uncorrected, mainly distal, hypospadias have shown conflicting results. Early reports indicate normal voiding, sexual function and high satisfaction with penile appearance, despite an abnormal position of the urethral meatus [351,352]. More recent studies have reported urinary spraying, urinary obstruction, penile curvature, coital pain and dissatisfaction with genital appearance in adult men with untreated hypospadias [353-355]. Notably, more than half of these men opted for surgical correction [353,354].

9.5.1. Indication for reconstruction and therapeutic objectives

Therapeutic decision-making regarding hypospadias surgery includes distinguishing between functionally essential and aesthetically feasible procedures. Aspects to be considered are voiding, sexual/reproductive function and cosmetic appearance.

Indications for surgery may be:

• proximally located (ectopic) meatus causing ventrally deflected or spraying urinary stream;
• meatal stenosis;
• ventral curvature of the penis;
• preputial hood; and
• penoscrotal transposition.

As all surgical procedures carry the risk of complications, thorough preoperative counselling of the caregiver is crucial to reduce the chance of decisional regret.

To achieve an overall acceptable functional and cosmetic outcome, the penile curvature must be corrected with an adequate size neourethra. The meatus should be glandular, and the penile shaft should have proper skin coverage [356]. The use of magnifying loupes and fine synthetic absorbable suture materials (6.0-7.0) are required. As in any penile surgery, exceptional prudence should be adopted with the use of cautery. Bipolar cautery is recommended. Knowledge of a variety of surgical reconstructive techniques, wound care and postoperative treatment is essential for a satisfactory outcome.

9.5.2. Preoperative hormonal treatment

There is inconclusive evidence to support the benefits of preoperative hormone therapy. The treatment is usually limited to patients with proximal hypospadias, a small-appearing penis, reduced glans circumference or narrow urethral plate [357-362].

There are concerns regarding the negative impact of testosterone on wound-healing and increased bleeding during surgery. Cessation of therapy is recommended one or two months prior to surgery to avoid adverse effects during or after surgery [363].

9.5.3. Age at surgery

The age at surgery for primary hypospadias repair is usually 6-18 months [356,364,365]. Age at surgery is not a risk factor for urethroplasty complications in prepubertal tubularised incised plate urethroplasty (TIP) repair [364]. Complication rate after primary TIP repair was 2.5 times higher in adults than in the paediatric group, according to a prospective controlled study [366].

9.5.4. Penile curvature

Some degree of penile curvature is common in hypospadias, and its severity is related to the severity of urethral abnormality. An erection test performed during hypospadias repair allows assessment of the degree of curvature. The use of measurement tools such as a goniometer or apps appears to improve accuracy compared to eyeballing assessment [367]. What degree of curvature is found to be clinically significant may differ between patients. Overall, curvature of 30 degrees or more is deemed to warrant correction [368].

For ventral curvature correction, a stepwise approach is recommended. The first step is degloving the penis (skin chordee) and excising abnormal connective tissue (chordee) on the ventral side of the penis [369].

In distal hypospadias, the urethral plate rarely causes curvature, as it has well characterised connective tissue [370,371]. In severe hypospadias, curvature may be due to hinging of the urethral plate, which requires transection prior to ventral lengthening or dorsal plication. Urethral plate without transection is not recommended due to the risk of ventral curvature recurrence (20%) and stricture formation (17%) [368].

Residual curvature is believed to be caused by corporeal disproportion and requires adaptation of the corpora to enable straightening of the penis. This can be achieved using various techniques based on either dorsal shortening or ventral lengthening. Dorsoplication with or without excision of tunica albuginea (Nesbit plication) can be performed with or without elevation of the neurovascular bundle. The drawback of all dorsoplication techniques is shortening of the penis and potentially decreased sensitivity [372]. Penile length is one of the main reasons for dissatisfaction following hypospadias repair [368]. Ventral lengthening by various corporotomy techniques, with or without covering the defect, is safe and does not have these unwanted side-effects [373].

Several studies have suggested that, in cases of severe curvature ventral, lengthening may be superior to dorsoplication [372,373]. The incidence of curvature-recurrence is less common with ventral lengthening than with dorsoplication (5% vs. 25%) [373], regardless of the technique used. Common procedures include multiple transverse corporotomies (such as fairy cuts or three corporotomies) or a single, wider corporoplasty. This is often covered by tunica vaginalis, although other tissues may have more contractions or are still under investigation [373]. Novel techniques using taping or stretching require further studies [374].

Risk factors for recurrence of ventral curvature are also related to the technique of urethral reconstruction. It has been shown that TIP for proximal hypospadias has a high recurrence rate of ventral curvature (26%). Conversely, the chosen method for penile straightening may impact the choice of urethral reconstruction. There is increasing evidence that corporoplasty with graft covering should not be performed simultaneously with urethral graft reconstruction [368].

9.5.5. Urethral reconstruction

The mainstay of hypospadias repair is preservation of the well-vascularised urethral plate and its use for urethral reconstruction has become standard practice in hypospadias repair [371]. Mobilisation of the corpus spongiosum/urethral plate and the bulbar urethra decreases the need for urethral plate transection [375]. The use of a penile tourniquet during hypospadias repair can reduce operative time and improves intraoperative hemostasis without affecting postoperative outcomes [376].

If the urethral plate is wide, it can be tubularised following the Thiersch-Duplay technique. If the plate is too narrow to be simply tubularised, a midline incision may facilitate subsequent tubularisation according to the TIP technique described by Snodgrass-Orkiszewski. This technique has become the treatment of choice in distal and mid-penile hypospadias [377-380]. If the incision of the plate is deep, an inlay graft with inner preputial skin or buccal mucosa may be considered to reduce the risk of stenosis in primary repairs [381]. This also enables extension of the incision beyond the end of the plate to prevent meatal stenosis [382,383]. For distal forms of hypospadias, a wide range of other techniques is available (Figure 4). The onlay technique using a preputial island flap is a good option for proximal hypospadias, or if the urethral plate is unsuitable for tubularisation [384]. Despite initial reports the use of TIP for proximal hypospadias repair is currently subject of debate.

If the continuity of the urethral plate cannot be preserved, single- or multi-staged repairs are used. Single-stage techniques include modifications of the tubularised flap (Duckett tube), such as a tube-onlay, an inlay-onlay flap or onlay flap on albuginea [385-387]. Alternatively, the Koyanagi-Hayashi technique is used [388-391]. Two (or more) staged procedures have become preferable over the past few years because of lower recurrence of ventral curvature and more favourable results, with variable long-term complication rates [382,383,385,392-396].

Recent studies indicate that several techniques can characterise the incidence of urinary fistulas. Sufficient dissection and good tissue handling are essential. Further, adequate covering of the urethral reconstruction appears most important. The use of tunica vaginalis may yield better results than dartos fascia. If dartos fascia is used, a double-layer technique is recommended [397,398]. New techniques for covering the neourethra are under investigation [399].

Figure 4: Algorithm for the surgical management of hypospadiasDSD = differences of sex development; Duckett = preputial hood onlay flap; GAP = glandular approximation procedure; MAGPI = meatal advancement and glanuloplasty incorporated; Mathieu = foreskin onlay flap; Snodgraft = preputial inlay graft; TIP = tubularised incised plate urethroplasty.

The choice of surgical technique is based on the severity of the urethral abnormality, as well as severity of curvature. If transection of the urethral plate is required for straightening, this influences the choice of urethral reconstruction.

9.5.6. Redo hypospadias repairs

No definitive guidelines can be provided for redo hypospadias repair. All the above-mentioned procedures are used in different ways. It is essential to emphasise individualised treatment tailored to the specific needs of the patient and the anatomical status of the urethral plate and surrounding tissues.

9.5.7. Penile reconstruction following formation of the neo-urethra

Following formation of the neourethra, the procedure is completed by glansplasty and by reconstruction of the penile skin. If there is a shortage of skin covering, the preputial double-face technique or placement of the suture line into the scrotum according to Cecil-Michalowski is used.

In countries in which circumcision is not routinely performed, preputial reconstruction can be considered if the prepuce is not required for urethral reconstruction or ventral skin coverage. It does not increase the risk of urethral complications, such as fistula formation, or the likelihood of reoperation [400]. This approach is considered a safe option, with a low risk of specific complications, such as preputial dehiscence (7-17%) and secondary phimosis (1.5%) [400-402]. In minor variants of hypospadias, isolated preputial reconstruction may be the procedure of choice to conceal the urethral malformation while avoiding the risks associated with urethroplasty.

9.5.8. Urine drainage and wound dressing

Urine is drained transurethral (e.g. dripping stent) or with a suprapubic tube. No drainage after distal hypospadias repair is another option [403,404]. There is no strong evidence that the type of stent material (transurethral stents) impacts surgical outcome [405]. Similarly, there is no evidence that the type of dressing influences outcomes in hypospadias repair [406]. There is no consensus on optimal duration of stenting and dressing [403,404,406,407].

Prophylactic antibiotics in hypospadias repair have not been shown to reduce the rate of postoperative surgical site infection or UTI, nor other long-term complications of surgery. The majority of evidence arises from distal hypospadias repair [408-410].

9.5.9. Analgesia (regional blocks)

Caudal blocks and peripheral nerve blocks (penile nerve blocks) are commonly used methods for perioperative analgesia in hypospadias surgery. All have been shown to have adequate postoperative analgesic properties [411-413]. The type of analgesic block has not shown to be associated with the risk of developing complications following primary hypospadias (all grades of hypospadias) correction in children [413-415].

9.6. Outcomes and complications

Outcomes in hypospadias repair are influenced by several key factors, including the severity of the condition, the patient’s surgical history, the surgeon’s experience and the surgical technique. Long-term follow-up is essential to assess both functional and aesthetic success, as well as to detect late complications.

9.6.1. Factors influencing outcomes

The following factors are known to influence outcomes:

• Severity of hypospadias: The complexity of the hypospadias plays a significant role in determining complication rates and the likelihood of success. Distal hypospadias repairs generally have high success rates, ranging from 85% to 90% in primary procedures [416]. On the other hand, proximal hypospadias presents a greater surgical challenge, with complication rates between 14% and 68%, reflecting the increased complexity of the condition [384,417-419].
• Previous surgical history: Patients who require redo surgeries face a higher risk of complications such as urethral stricture and fistulas, largely due to scar tissue and reduced vascularity. The complication rate for redo surgeries is approximately 23.3%, compared to 12.2% for primary repairs [416].
• Surgeon experience: Surgeons with greater experience and higher surgical volumes consistently report fewer complications and improved long-term outcomes, especially in complex cases of proximal hypospadias The surgeon’s preference and familiarity with the chosen technique can also influence the outcomes [368,385,420].
• Surgical technique: Different techniques yield varying outcomes and complications. For distal hypospadias, the TIP urethroplasty is a widely accepted technique with a low complication rate (below 10%) [416]. Tubularised incised plate urethroplasty repairs in distal hypospadias have fistula rates between 3% and 4%, similar to those seen with the Mathieu technique [381]. For proximal hypospadias, more-complex approaches are often required, and staged repairs are preferred. These show significantly lower overall complication rates (21% compared to 42% for one-stage repairs), including reduced risk of fistula (12% vs. 19%), meatal stenosis (8% vs. 17%) and urethral strictures (8% vs. 13%) [392,418]. In severe cases requiring staged repairs using buccal mucosa grafts, complications such as graft fibrosis occur in more than one-third of patients following the second stage [396,421,422].

9.6.2. Complications

Overall, fistula rates range from 5% to 50%, depending on the complexity of the case [416,417]. Glans size, specifically a width of less than 14mm, is an independent risk factor for urethral complications such as fistula formation as well as stenosis. Glans size should be considered when planning the surgical approach [407,423]. Certain technical choices may reduce the chance of fistulas, such as the use of flaps to provide additional coverage of the neourethra (see Section 10.3 on management) [399,417].

Meatal stenosis occurs in 5% to 15% of cases, particularly when the meatus is reconstructed under tension. The use of inlay grafts has been shown to reduce the risk of meatal stenosis by 66% compared to TIP alone, although these grafts do not significantly improve other long-term outcomes, such as fistula formation or glans dehiscence [381]. Urethral strictures occur in 8% to 13% of cases, especially in proximal hypospadias repairs. Even with two-stage procedures, strictures may still develop and require further surgical intervention in more-severe cases [399].

Recurrent penile curvature is a significant complication observed in proximal hypospadias repairs. Staged repairs have been shown to have lower risk of curvature recurrence than TIP in proximal hypospadias. Tubularised incised plate urethroplasty should only be performed in cases with no curvature or minimal curvature less than 30 degrees [368,392,424]. Additional surgeries to correct curvature may be needed as the child grows, particularly during puberty [392,420,425].

The incidence of glans and wound dehiscence ranged from 9% to 17%, with a higher likelihood in patients with more severe hypospadias. Small glans size, proximal meatal location, single-stage repairs and associated penile curvature are key risk factors for glans dehiscence following hypospadias surgery. Despite this, long-term functional outcomes are generally unaffected, although some patients seek aesthetic corrections [416,426].

9.7. Long-term follow-up and transition

Long-term follow-up after hypospadias repair is essential, as significant rates of complications have been reported, which may occur early as well as several years after surgery [427,428]. A recent study showed a total reoperation rate of 48% in the first fifteen years of life. This rate was highest in the subgroup of proximal hypospadias [400].

9.7.1. Voiding

Obstructive urinary flow curves are frequently observed after hypospadias repair. While most children remain asymptomatic, conducting uroflow assesessments is essential during follow-up to monitor if the obstructive pattern worsens or becomes associated with lower urinary tract symptoms [429-431].

9.7.2. Penile appearance

Various scoring systems for evaluating surgical outcomes and cosmetic satisfaction have been developed [432,433]. Studies applying these scoring systems in postpubertal boys have revealed that caregivers and urologists express less satisfaction with penile appearance compared to the patients themselves. Moreover, many patients report equal satisfaction with the penile appearance compared to age-matched controls [433-436].

Differences in penile length compared to age-matched controls have correlated negatively to the overall patient satisfaction with penile appearance, especially in men with proximal hypospadias [437-439].

Studies on the long-term results of hypospadias repair are generally characterised by a high loss to follow-up, heterogeneous data, risk of selection bias and lack of validated measurement tools.

9.7.3. Sexual function and fertility

Overall, studies have shown good self-reported sexual function and satisfaction with sexual life in adolescent boys and men following hypospadias repair during infancy. The severity of hypospadias and a high number of operations are key factors that may negatively influence psychosexual well-being [438,440].

Lower paternity rates have been reported in men with hypospadias, particularly in severe cases and concomitant cryptorchidism, when comparing with healthy age-matched controls. The aetiology is multifactorial and may include the presence of persisting curvature, which can make intercourse with penetration difficult, reduced semen quality or ejaculation problems [438].

9.7.4. Health-related quality of life

There is currently a lack of disease-specific, health-related quality of life (HRQoL) tools for hypospadias patients [441].

9.7.5. Transition

See Chapter 27 on transitional urology.

9.8. Summary of evidence and recommendations for the management of hypospadias