Paediatric Urology

11. VARICOCELE IN CHILDREN AND ADOLESCENTS

11.1. Epidemiology, aetiology and pathophysiology

Varicocele is defined as an abnormal dilatation of testicular veins in the pampiniformis plexus caused by venous reflux. It is unusual in boys under ten years of age and becomes more frequent at the start of puberty. Varicocele is found in 14-20% of adolescents, with a similar incidence during adulthood. It appears mostly on the left side (78-93% of cases). Right-sided varicoceles are less common and are usually noted only when bilateral varicoceles are present and seldom occur as an isolated finding [451-453].

Varicocele develops during accelerated body growth and increased blood flow to the testes, by means of a mechanism that is not clearly understood. Genetic factors may be present [454,455]. An anatomic abnormality leading to impaired venous drainage is expressed by the considerable prevalence of the left-side condition, in which the internal spermatic vein drains into the renal vein. Varicocele can induce apoptotic pathways due to heat stress, androgen deprivation and accumulation of toxic materials [456,457]. In 70% of patients with grade II and III varicocele, left-testicular volume loss was found. Abnormal reproductive hormonal levels (increased serum levels of FSH and LH and decreased levels of inhibin B) and semen quality were reported in varicocele patients and were directly related to varicocele severity [458-460]. Severe histological damage is found in 20% of adolescents affected, with abnormal findings in 46% of affected adolescents. Histological findings are similar in children or adolescents and in infertile men. Fertility problems will arise in approximately 20% of adolescents with varicocele [461]. The adverse influence of varicocele increases with time.

11.2. Classification systems

Varicocele is classified into three grades [462]:

• Grade I - Valsalva positive (palpable at Valsalva manoeuvre only);
• Grade II - palpable (palpable without the Valsalva manoeuvre); and
• Grade III - visible (visible at distance).

11.3. Diagnostic evaluation

Varicocele, being mostly asymptomatic, is generally noticed by the patient or caregivers or discovered by the paediatrician at a routine visit. The diagnosis depends upon the clinical finding of a collection of dilated and tortuous veins in the upright posture; the veins are more pronounced when the patient performs the Valsalva manoeuvre. Clinical examination should include evaluation of the size of both testicles to detect a smaller testis.

In prepubertal boys and in isolated right varicocele, a renal US should be routinely added to rule out a secondary varicocele due to any retroperitoneal tumour extending into the renal vein and inferior vena cava.

Testicular volume is measured by US examination or by orchidometer. In adolescents, a testis that is smaller by > 2mL or 20% compared to the other testis is considered hypotrophic [463]. Venous reflux into the plexus pampiniformis is diagnosed using Doppler US colour flow mapping in the supine and upright position and with the Valsalva manoeuvre [464]. Venous reflux detected in US only is classified as subclinical varicocele. Severity of reflux on Doppler US was shown to correlate with testicular damage [459].

Sperm analysis in principle allows assessment of testicular function, but the World Health Organization (WHO) parameters are not intended for prepubertal patients, and spontaneous improvements of abnormal sperm analyses has been observed in prepubertal patients [465]. Moreover, sperm analysis encounters cultural/ethical barriers in children [466]. Therefore, semen analysis in not widely used and is generally recommended only in older adolescents.

To assess testicular injury in adolescents with varicocele, supranormal FSH and LH responses to the luteinising hormone-releasing hormone (LHRH) stimulation test are considered reliable, because histopathological testicular changes have been found in these patients [467,468].

11.4. Management

There is no evidence that treatment of varicocele at paediatric age will offer a better andrological outcome than an operation performed later and earlier diagnosis should not convey a more pressing need to intervene [469,470]. Beneficial effect of pubertal screening and treatment for varicocele regarding the preservation of fertility and final chance of paternity is controversial [471-473]. The recommended indication criteria for correction for varicocele in children and adolescents are [452]:

• varicocele associated with a small testis (this should be confirmed during two subsequent visits performed six months apart), because asynchronous testicular growth can account for a temporary asymmetry, including in a considerable number of healthy adolescents [474].

Additional scenarios in which varicocele treatment can be considered on a case-by-case basis include:

• symptomatic varicocele [473]. Pain is present in 2-10% of varicoceles. The association between varicocele and pain is unclear and patients should be informed that pain can persist after varicocelectomy in 20% of cases [475];
• additional testicular condition affecting fertility such as a contralateral testicular condition;
• bilateral palpable varicocele;
• pathological sperm quality (in older adolescents); and
• cosmetic reasons related to scrotal swelling.

A reduced total testicular volume (left + right) in comparison with normal testes is a promising indication criterion, once the normal values are available [460,469]. Repair of a large varicocele, causing physical or psychological discomfort, may also be considered. Other varicoceles should be followed up until a reliable sperm analysis can be performed.

11.4.1. Surgical management

Surgical intervention is based on ligation or occlusion of the internal spermatic veins.

Ligation is performed at various levels:

• inguinal (or subinguinal) microsurgical ligation; and
• suprainguinal ligation, using open or laparoscopic techniques [476-479].

The advantage of inguinal (or subinguinal) microsurgical ligation is the lower level of invasiveness of the procedure, while the advantage of the latter is a considerably lower number of veins to be ligated and safety of the incidental division of the internal spermatic artery at the suprainguinal level.

For surgical ligation, some form of optical magnification (microscopic or laparoscopic) should be used because the internal spermatic artery is 0.5mm in diameter at the level of the internal ring [476,478]. In a suprainguinal approach, an artery-sparing varicocelectomy may not offer any advantage in regard to catch-up growth and is associated with a higher incidence of recurrent varicocele [480,481].

Lymphatic-sparing varicocelectomy is preferred to prevent hydrocele formation and testicular hypertrophy development and to achieve a better testicular function according to the LHRH stimulation test [476,477,482,483]. The methods of choice are subinguinal or inguinal microsurgical (microscopic) repairs or suprainguinal open or laparoscopic lymphatic-sparing repairs [476,478,484,485]. In suprainguinal open or laparoscopic lymphatic-sparing repairs, intrascrotal/intratesticular injection of isosulfan blue was recommended to visualise the lymphatic vessels [486,487].

11.4.2. Radiological management

Angiographic occlusion of the internal spermatic veins also meets the requirements of lymphatic sparing repair. It is based on retrograde or antegrade sclerotisation of the internal spermatic veins [488,489]. However, although this method is less invasive and may not require general anaesthesia, it is associated with radiation burden, which is less controllable in the antegrade technique [452,488,489].

A low to moderate level of evidence exists showing that radiological or surgical treatment of adolescent varicocele is associated with improved testicular size/growth and sperm concentration. Several authors reported testicular catch-up growth after varicocelectomy in adolescents [490,491]. An average proportion of catch-up growth of 76.4% (range: 52.6-93.8%) has been found according to a meta-analysis [492]. However, this may partly be attributable to testicular oedema associated with the division of lymphatic vessels [482]. Improvement in sperm parameters has been demonstrated after adolescent varicocelectomy [467,493-495]. In one study, microsurgical varicocele repair in adolescents with varicocele significantly increases paternity rates and decreases time to conception postoperatively, but this must be confirmed in other series. The ultimate effects on fertility and paternity rates are not known [496].

The Panel conducted a systematic review and meta-analysis regarding the treatment of varicocele in children and adolescents [497]. Of 1,550 articles identified, 98 articles including 16,130 patients were eligible for inclusion (12 RCTs, 47 NRSs and 39 case series). The following paragraphs summarise the key findings.

The meta-analysis of the twelve RCTs revealed that varicocele treatment improved testicular volume (mean difference 1.52ml, 95% CI: 0.73-2.31) and increased total sperm concentration (mean difference 25.54, 95% CI: 12.84-38.25) when compared with observation. Lymphatic sparing surgery significantly decreased hydrocele rates (p = 0.02) and the OR was 0.08 (95% CI: 0.01, 0.67). Due to the lack of RCTs, it was not possible to identify a surgical technique as being superior to the others. It remains unclear whether open surgery or laparoscopy is more successful for varicocele treatment (OR ranged from 0.13 to 2.84).

The success rates of the treatment (disappearance of varicocele) were between 85.1% and 100%, whereas the complication rates were between 0% and 29% in the included studies. The most common complication reported was hydrocele. Resolution of pain after treatment was more than 90% in the reported series.

The major reason for varicocele recurrence is the persistence of branched spermatic veins that were not ligated during the initial repair. Treatment of recurrence is warranted only in those patients with clinical recurrence that show no improvement in testicular asymmetry or remain symptomatic. Treatment of recurrence can be surgical or by means of embolisation. A technique different from the primary repair is generally recommended to operate in a virgin field [498].

In conclusion, moderate evidence exists regarding the benefits of varicocele treatment in children and adolescents in terms of testicular volume and sperm concentration. Current evidence does not demonstrate superiority of any of the surgical/interventional techniques regarding treatment success. Lymphatic-sparing surgery significantly decreases hydrocele formation. Long-term outcomes, including paternity and fertility, remain unknown.

11.5. Summary of evidence and recommendations for the management of varicocele