10
Treatment Strategy for the Adolescent Varicocele Samuel P. Robinson, MD, Lance J. Hampton, MD, Harry P. Koo, MD* A varicocele is a dilatation of the testicular vein and the pampiniform venous plexus within the sper- matic cord. Although rare in pediatric populations, the prevalence of varicoceles markedly increases with pubertal development to approximately 15% by the late teenage years, a rate similar to that in adult populations. 1,2 Varicoceles are progressive lesions that may hinder testicular growth and func- tion over time and are the most common and correctable cause of male infertility. The incidence of varicocele in men with abnormal semen is 25% compared with almost 12% in men with normal semen. 3 Approximately 40% of men with primary infertility have a varicocele, and more than half of them experience improvements in semen parame- ters after varicocelectomy. 4–6 However, experts continue to debate the efficacy of surgical inter- vention in improving fertility as evidenced by a recent Cochrane review, which suggested that ‘‘there is no evidence that treatment of varicoceles in men from couples with otherwise unexplained subfertility improves the couple’s chance of conception.’’ 7 Furthermore, as only 20% of men with a documented varicocele suffer from infer- tility, 3 care must be taken in the clinical evaluation of a varicocele, and treatment must be tailored to the specific subgroup of individuals most likely to benefit from a surgical intervention. The decision to treat adolescents with varico- cele is a controversial one. Most physicians agree that treating all adolescent boys with varicocele, thus subjecting a large percentage of boys to potentially unnecessary surgery, would be inappropriate, costly, and not without ethical considerations. However, waiting until patients present themselves as adults with possible irre- versible infertility would be equally unacceptable. The task for pediatricians and urologists is to iden- tify those adolescents who are at greatest risk for infertility in adulthood, in an effort to offer early surgical intervention to those most likely to benefit. ANATOMY AND VARICOCELE FORMATION The formation of a varicocele has been attributed predominantly to anatomic variance, increased pressure in the left renal vein, and incompetent or congenitally absent valves. Approximately 90% of varicoceles are left sided. Several anatomic differences between the right and left testicular (internal spermatic) veins are thought to contribute to this predominance. Although highly variable, the left system usually consists of 1 or more veins within the spermatic cord that coa- lesce in the retroperitoneal space to become the testicular vein. The left testicular vein inserts into the left renal vein at a right angle, whereas the right testicular vein joins the inferior vena cava at an ob- lique angle. The relative greater blood flow in the inferior vena cava is thought to augment drainage on the right. 8 The left testicular vein, however, is 8 to 10 cm longer (more craniad) than the right, with a proportional increase in pressure head. Increases in left renal vein pressure also have been noted secondary to 2 nutcracker phenom- enon mechanisms. 9 The proximal nutcracker Division of Urology, Virginia Commonwealth University School of Medicine, 1200 East Broad Street, Richmond, VA 23298-0118, USA * Corresponding author. E-mail address: [email protected] KEYWORDS Varicocele Adolescent Infertility Urol Clin N Am 37 (2010) 269–278 doi:10.1016/j.ucl.2010.03.011 0094-0143/10/$ – see front matter ª 2010 Published by Elsevier Inc. urologic.theclinics.com

Treatment Strategy for the Adolescent Varicocele

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Page 1: Treatment Strategy for the Adolescent Varicocele

Treatment Strategyfor the AdolescentVaricocele

Samuel P. Robinson, MD, Lance J. Hampton, MD,Harry P. Koo, MD*

KEYWORDS

� Varicocele � Adolescent � Infertility

A varicocele is a dilatation of the testicular vein andthe pampiniform venous plexus within the sper-matic cord. Although rare in pediatric populations,the prevalence of varicoceles markedly increaseswith pubertal development to approximately 15%by the late teenage years, a rate similar to that inadult populations.1,2 Varicoceles are progressivelesions that may hinder testicular growth and func-tion over time and are the most common andcorrectable cause of male infertility. The incidenceof varicocele in men with abnormal semen is 25%compared with almost 12% in men with normalsemen.3 Approximately 40% of men with primaryinfertility have a varicocele, and more than half ofthem experience improvements in semen parame-ters after varicocelectomy.4–6 However, expertscontinue to debate the efficacy of surgical inter-vention in improving fertility as evidenced bya recent Cochrane review, which suggested that‘‘there is no evidence that treatment of varicocelesin men from couples with otherwise unexplainedsubfertility improves the couple’s chance ofconception.’’7 Furthermore, as only 20% of menwith a documented varicocele suffer from infer-tility,3 care must be taken in the clinical evaluationof a varicocele, and treatment must be tailored tothe specific subgroup of individuals most likely tobenefit from a surgical intervention.

The decision to treat adolescents with varico-cele is a controversial one. Most physicians agreethat treating all adolescent boys with varicocele,thus subjecting a large percentage of boys topotentially unnecessary surgery, would be

Division of Urology, Virginia Commonwealth University SVA 23298-0118, USA* Corresponding author.E-mail address: [email protected]

Urol Clin N Am 37 (2010) 269–278doi:10.1016/j.ucl.2010.03.0110094-0143/10/$ – see front matter ª 2010 Published by E

inappropriate, costly, and not without ethicalconsiderations. However, waiting until patientspresent themselves as adults with possible irre-versible infertility would be equally unacceptable.The task for pediatricians and urologists is to iden-tify those adolescents who are at greatest risk forinfertility in adulthood, in an effort to offer earlysurgical intervention to those most likely to benefit.

ANATOMY AND VARICOCELE FORMATION

The formation of a varicocele has been attributedpredominantly to anatomic variance, increasedpressure in the left renal vein, and incompetentor congenitally absent valves. Approximately90% of varicoceles are left sided. Severalanatomic differences between the right and lefttesticular (internal spermatic) veins are thought tocontribute to this predominance. Although highlyvariable, the left system usually consists of 1 ormore veins within the spermatic cord that coa-lesce in the retroperitoneal space to become thetesticular vein. The left testicular vein inserts intothe left renal vein at a right angle, whereas the righttesticular vein joins the inferior vena cava at an ob-lique angle. The relative greater blood flow in theinferior vena cava is thought to augment drainageon the right.8 The left testicular vein, however, is 8to 10 cm longer (more craniad) than the right, witha proportional increase in pressure head.

Increases in left renal vein pressure also havebeen noted secondary to 2 nutcracker phenom-enon mechanisms.9 The proximal nutcracker

chool of Medicine, 1200 East Broad Street, Richmond,

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Robinson et al270

phenomenon describes compression of the leftrenal vein as it passes between the aorta andsuperior mesenteric arteries. The distal mecha-nism involves retrograde blood flow through thedeferential and external spermatic veins causedby compression of the left common iliac vein asit courses under the left common iliac artery.

Congenitally absent or incompetent valves haveclassically been thought to be the primary cause ofvaricocele formation. Subsequent research hasshown that there are males without varicocelewho have incompetent or absent testicular veinvalves and males with varicocele who havecompetent valves.10,11 Even with normal valves,dilation of the testicular vein can cause functionalincompetence as a result of loss of coaptation.12

Valve pathology may not be a sole cause, but itcertainly contributes to varicocele formation andseverity. Alterations in venous architecture at themicroscopic level may also play a role in the path-ogenesis of varicocele. However, it remains diffi-cult to differentiate between cause and effect inanatomic analysis, as evidenced by several recentstudies, which documented significant histologicchanges in the amount of connective tissuepresent in the vein wall of the pampiniform plexusthat appeared to have a linear correlation with vari-cocele grade.13,14

Although the exact mechanisms have yet to beelucidated, several physical findings have beenfound to be associated with an increased risk fordeveloping varicocele in adolescence. A lowbody mass index has been found to be associatedwith the development of varicocele in adoles-cence. Increased penile length and circumferenceas well as rapid pubertal development were alsofound to be the independent risk factors for thedevelopment of varicocele.15,16

PATHOLOGIC FINDINGS RELATEDTO TESTICULAR DYSFUNCTIONIN ASSOCIATION WITH VARICOCELE

The association between varicocele and testiculardysfunction has been observed by scientists andphysicians for nearly 2000 years, dating back tothe Greek physician, Celsus, who noted a testicularsize discrepancy in the face of dilated veins withinthe scrotum, suggesting that the discrepancy re-sulted in impaired testicular nutrition. Since theidea resurfaced in medical texts in the late1800s, varicocele has been documented in asso-ciation with a variety of conditions including testic-ular hypotrophy, an abnormal gonadotropin axis,histologic changes within the testicle, abnormalspermatogenesis, and ultimately, infertility.17

However, despite the existence of a growing

body of literature defining these associations,a direct causal relationship has yet to be confirmedconclusively. As such, debate continues on thepathologic effects of varicocele.

Testicular Hypotrophy

The most well-documented abnormality associ-ated with clinical varicocele is testicular hypotro-phy. A large multicenter study3 performed by theWorld Health Organization found an associationbetween varicocele and ipsilateral testicularvolume; Mori and colleagues18 took it a stepfurther to define a relationship between varicocelegrade and incidence of testicular hypotrophy inadolescents. Although testicular size remains aneasily observable clinical phenomenon in the pres-ence of varicocele, its relationship to testiculardysfunction, as defined by abnormal semen anal-ysis results, remains more difficult to quantify inadolescents.

Impaired Spermatogenesis

In adults, the most common findings on semenanalysis are decreased motility, decreased spermdensity, and increased number of pathologicsperm forms.3,19 Furthermore, a variety of histo-logic changes related to testicular dysfunctionhave been documented in the results of testicularbiopsy in males with varicocele, including Leydigcell hyperplasia, decreased number of spermato-gonia per tubule, decreased spermatogenesisand maturation arrest, sloughing of germinalepithelium, and interstitial fibrosis.20,21 Becausethe adult testicle is composed mostly of seminif-erous and germinal cells, it is not surprising tofind a correlation between testicular volume andfunction as defined by semen analysis in thisgroup.22,23 This correlation seems to be consistentwhen related to dysfunction and postoperativeimprovement.24,25 Although a wealth of researchdescribes abnormal semen analysis results in thepresence of varicocele, the heterogeneity ofparameters used to define abnormal and the rela-tively large number of confounding factors relatedto the desired outcome (successful pregnancy)continue to complicate the debate.

Identifying Pathology in Adolescents

Although the toxic effect of varicocele on semenparameters has been demonstrated in adoles-cents,19 the correlation between testicular hypo-trophy and abnormal spermatogenesis in thisage group has historically been harder to quantify.Haans and colleagues26 reported that adolescentswith pronounced left testicular growth failurehad significantly reduced sperm count, but

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Treatment Strategy for the Adolescent Varicocele 271

concentration, motility, and morphology wereunaffected. This lack of clear association inadolescents could potentially be explained inpart by the fact that left testicular growth failureoccurs before significant decreases occur insemen parameters. Furthermore, there were rela-tively few studies to compare semen analysis inadolescents, given the difficulty in obtaining spec-imens in this age group and ethical questionsregarding the psychological impact of theirprocurement. Researchers have defined a statisti-cally significant correlation between sonographictesticular volume and decreased sperm concen-tration and total motile sperm counts in adoles-cents as well as a relation with varicocelegrade.18,27 Addressing the subject of moleculardysfunction, another study documented anincrease in the number of sperm with abnormalDNA and a decrease in the number of spermwith normal DNA in adolescents with high-gradevaricocele, even when semen analysis result wasnormal.28

PROPOSED PATHOLOGIC MECHANISMS

Although the association of clinically detectablevaricocele with testicular hypotrophy, an abnormalgonadotropin axis, histologic changes, abnormalspermatogenesis, and infertility has been clearlydocumented in the literature, the exact mecha-nism whereby varicocele induces pathologicchange has yet to be elucidated. Many theorieshave been postulated on the subject, includingincreased testicular temperature, hypoxia, refluxof adrenal and renal metabolites, and generationof reactive oxygen species (ROS).

Hyperthermia

Elevated scrotal and testicular temperature is themost widely accepted mechanism for testiculardysfunction. Experimentally induced varicoceleincreases scrotal temperature and is reversiblewith surgical correction.29,30 Hyperthermia hasconsistently been shown to negatively affectgerm cell function, proliferation, and subsequentfertility.31 Furthermore, scrotal cooling and, conse-quently, testicular cooling have been documentedto improve semen quality.32 Varicocelectomy inhuman studies has been shown to normalizetemperature, with subsequent increases in spermcount.33–35 When comparing infertile men withvaricocele to normal controls, as well as to menwith varicocele and normal fertility, infertile menwith varicocele were shown to have increasedintrascrotal temperatures.36,37 Several studieshave sought to define the molecular basis for infer-tility in association with elevated testicular

temperatures in both adult and adolescent maleswith varicocele. It would seem that the downregu-lation of heat shock proteins may be associatedwith infertility in these groups.38,39 Furthermore,an increase in the expression of heat shockproteins after varicocelectomy has beendocumented.39,40

Hypoxia

Although early studies did not support theproposal that venous stasis and reduced bloodflow of the testicular vessels resulted in hypoxia,several recent publications have proposed a directlink between impaired testicular drainage andtissue hypoxia. These studies suggest that tissuedamage is the result of impaired testicular micro-circulation secondary to increased hydrostaticpressure rather than global hypoxia.41 Thisproposal has been supported by studies identi-fying increased expression of hypoxia-induciblefactor-1 alpha in association with varicocele inhuman and animal models.42

Reflux of Renal and Adrenal Metabolites

Reflux of adrenal and renal metabolites has beenproposed as a mechanism for testicular damagein men with varicocele. Research has been incon-clusive, and experimental studies have shown thattoxic effects of varicocele do not require adrenalcontribution and that reflux may not occur.43 Adre-nomedullin, a potent vasodilator expressed inadrenal and kidney tissues but not in the testes,has been isolated in blood samples from thetesticular veins of men with varicocele.44 In ratmodels, varicocele-induced testicular damagewas found to be enhanced in subjects with viableadrenal glands when compared with those inwhom a unilateral adrenalectomy was performedbefore varicocele induction.45 Further research isrequired to determine if adrenomedullin playsa role in the formation of or toxicity associatedwith varicocele.

ROS and Oxidative Stress

Venous blood from varicoceles of infertile men hasshown increased production of nitric oxide, itsactive metabolites, and ROS that are known toplay a role in sperm dysfunction.46–48 Theseincreased levels have been shown to correlatewith the severity of varicocele.48 Varicocele alsoreduces antioxidant defenses, potentially addingto the localized oxidative stress (OS).49 Severalstudies reported a decrease in markers of ROS-associated damage and an improvement in anti-oxidant levels after varicocelectomy.50,51 Althoughthe relation between varicocele and OS is clear,

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the exact cause of OS in this case has yet to beclearly defined. Nevertheless, numerous mecha-nisms have been proposed to identify the originof OS in patients with varicocele, including therole of cytokines (interleukin 1); increased expres-sion of leptin receptors; increased nitric oxidelevels resulting from hypoxia, as an inducer ofapoptosis and precursor of oxidants; and downre-gulation of glial cell line derived–neurotrophicfactor receptor (factor involved in spermatogen-esis).48 Whether these complex mechanisms arethe final common pathway for varicocele-inducedinfertility or an effect of testicular injury is stillunknown. Although few reports exploring theadministration of antioxidants in subfertile menwith varicocele have been produced, the use ofzinc, glutathione, and Chinese herbal remediescontaining a variety of antioxidants have shownsome promise.48

DIAGNOSIS

Typically, varicoceles are asymptomatic and de-tected in adolescents during routine physicalexamination. Occasionally, scrotal mass evalua-tions referred from primary care physicians arefound to be varicoceles. Differential diagnosesfor generally painless scrotal masses in adoles-cence include communicating hydrocele, hydro-cele of the spermatic cord, inguinal hernia,epididymal cyst, and spermatocele.

Patients should be examined in a warm room instanding and supine positions and with and withouta Valsalva maneuver. Classically, varicoceles aregraded according to the following criteria:

Grade 1 (small): palpable only with Valsalvamaneuver

Grade 2 (medium): palpable with the patientstanding

Grade 3 (large): visible through scrotal skin,palpable with the patient standing.

After examining in an upright position, thepatient should be reexamined in the supine posi-tion. Idiopathic varicocele is more prominent inthe upright position and disappears in the supineposition. Secondary varicoceles, especially onthe right side, can be caused by retroperitonealtumors or lymphadenopathy and do not changesize as noticeably as in the supine position.

An important part of the physical examination inall boys with varicocele is an accurate assessmentof testicular consistency (firmness) and volume.Although the assessment of testicular consistencyis subjective, a careful simultaneous comparisonof both testes may give the clinician additional

qualitative information about the overall conditionof the ipsilateral testis. Several methods are avail-able to measure the size of the testis, includingvisual comparison, calipers, Prader orchidometer(comparative ovoids), Takahira orchidometer(disc elliptical rings), and ultrasonography.Measurement of testis volume has been reportedto be assessed accurately and reproducibly byusing either a Prader or a disc orchidometer.52

However, ultrasonography should be consideredthe standard criterion for assessing testicularvolume. Results of ultrasonography have consis-tently shown high correlation with actual testisvolume and have been highly reproducible, withimproved detection of bilateral varicoceles andincreased sensitivity in the evaluation of volumedifferentials as compared with orchidometer.53,54

In a clinical study comparing Prader orchidome-ter and ultrasonography in adolescents with a vari-cocele, Costabile and colleagues55 found that24% of patients with growth arrest would havebeen missed and 14% would have been identifiedfalsely to have a significant size discrepancy ifmeasured by Prader orchidometer alone. Dia-mond and colleagues53 noted similar superiorityof ultrasonography for measuring testicularvolume; they recommend annual ultrasonographyof testis in adolescents with varicocele.

IDENTIFYING PATIENTS AT RISK

Left untreated, with time, in a subset of patients,the varicocele will continue to affect testiculargrowth, with loss of volume and progressive dete-rioration in semen parameters.56,57 In adults, treat-ment is straightforward and is proposed whenever(1) there is a palpable varicocele, (2) there is docu-mented infertility, (3) it has been confirmed thatthere is no female infertility problem, and (4) thereis at least 1 abnormality found on semen anal-ysis.58 In the adolescents, significant controversyexists regarding the appropriate methods of eval-uation for surgery. The diagnosis of varicoceleleads to additional questions about possible infer-tility and the need to establish clinical criteria forvaricocele repair. Currently, a variety of clinicaltests are available for identifying adolescents atrisk for infertility associated with varicocele.However, a consensus has yet to be reached onthe most appropriate combination of tests in eval-uation of adolescent varicocele. This topic remainsat the forefront of debate and research. Currently,clinical tests proposed in evaluation for surgicalintervention in adolescents with varicocele include(1) physical examination and radiologic evaluation,(2) biochemical tests, and (3) semen analysis.

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Treatment Strategy for the Adolescent Varicocele 273

Physical Examination and RadiologicEvaluation

Physical examination includes identification ofvaricocele grade and the measurement of testic-ular volume, as well as some novel approachesto ultrasound imaging to measure retrograde flowin the spermatic venous plexus. There remain con-flicting opinions about the correlation between thegrade of varicocele and its ultimate effect on thetestis. Some investigators have found no correla-tion between varicocele grade and testicular sizeor semen parameters,27 whereas others havenoticed that boys with severe varicoceles havesmaller ipsilateral testis and increasingly abnormalfindings in semen analysis in comparison withthose adolescents with lower-grade varico-celes.18,55,59 In an early study involving adolescentboys and young men aged 12 to 25 years, 34% ofsubjects with a grade-2 varicocele had testicularchanges, compared with 81% of those withgrade-3 varicocele. Within the grade-3 group, thepercentage of subjects aged 18 to 25 years withtesticular change reached almost 98%, illustratingthe progressive nature of varicocele-inducedtesticular damage and indicating that testicular hy-potrophy is almost inevitable in males with grade-3varicocele.60 Although the higher-grade varico-celes seem more concerning, varicocele gradeshould not be a sole determinant in recommendingtreatment.61

There is abundant literature confirming that vari-cocele is associated with testicular growth arrestin adolescents and that varicocele repair resultsin testicular catch-up growth.62–65 The risk fortesticular growth arrest also has been shown tobe time dependent and to correlate with varicoceleand reflux grade.66,67 However, according toa study by Zampieri and associates,68 involving465 patients, only 32% of patients had completecatch-up growth. Also, Preston and colleagues69

determined that a statistically significant numberof adolescents with varicocele and testicular-sizediscrepancy experience testicular catch-upgrowth as a normal function of development.Nevertheless, the relationship between testicularhypotrophy and infertility remains clear, anda recent study confirmed that size differentialsgreater than 10% between normal and hypotro-phic testicles correlated with a decreased spermconcentration and total motile-sperm count.27

Furthermore, this difference was found to increasedramatically when the size differential reached20%. These data would suggest that patientswith a persistent size differential of greater than20% should be offered surgical interventionwithout further investigation. Although a waiting

period is recommended for adolescents to assessfor resolution of size discrepancy, a recent studyproposed that peak retrograde flow velocities ofgreater than 38 cm/s (found to be a predictor ofpersistent asymmetry), when combined witha size differential of 20% or greater, negated theneed for such a waiting period.

Biochemical Tests

Biochemical tests are based on the integrity of thetestis and any effect of the varicocele on the hypo-thalamic-pituitary axis. At the testis level, seruminhibin levels reflect the integrity of the seminif-erous tubules and the function of Sertoli cells. Arecent study suggests that in adolescents, inhibinB levels are elevated in untreated varicocele anddirectly correlate with testicular volume.70

Because inhibin levels have been shown toimprove in men whose semen analysis improvedafter varicocelectomy, inhibin may have a rolepostoperatively as well.71 However, contradictionsexist among the studies, and there are not enoughdata to support the use of serum inhibin levels instratifying adolescents with varicoceles.72,73

The gonadotropin-releasing hormone (GnRH)stimulation test is based on the theory thatdamage to germinal epithelium results incompensatory stimulation of the pituitary glandand subsequent increase in the production offollicle-stimulating hormone (FSH) and luteinizinghormone (LH) by gonadotrophs. Several studiesdemonstrate an abnormal gonadotropin axis inmen with varicocele as evidenced by increasedFSH or LH response to administration ofGnRH.72,74 Although some would recommendthe GnRH stimulation test for adolescents as partof a standardized evaluation for surgery, theGnRH stimulation test has not been conclusivelyshown to be a good predictor of postsurgicalimprovement in adolescents.75–77

Semen Analysis

Semen analysis in men with varicoceles revealsdecreased motility, decreased sperm density,and more pathologic forms. By applying strictmorphologic criteria to semen analysis, varicocelerepair improves the seminal parameters in approx-imately 70% of patients, with the improvement inmotility being the most common.24,25

Over the last several years, researchers haveincreasingly come to use semen analysis in theevaluation of testicular dysfunction associatedwith adolescent varicoceles.78 Studies suggestthat the effect of varicocele on semen quality issimilar in adults and adolescents.79 In a study of

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88 boys, Laven and colleagues62 found a statisti-cally significant increase in sperm concentrationvalues 1 year after varicocele repair. No differ-ences in total sperm count, sperm motility, ormorphology were observed among postoperativevaricocele patients, normal healthy boys, and incontrols with untreated varicoceles. However,difficulties remain because established norms foradolescent semen analysis have yet to be defined.Semen analysis cannot adequately be performeduntil the subjects have progressed to the point inpubertal development necessary for adequateejaculation, and sample procurement continuesto raise several ethical questions.19,80 Neverthe-less, it would seem from current trends in the liter-ature that recommendations for the role of semenanalysis in evaluation of adolescent varicocele areforthcoming.

MANAGEMENT

Prophylactic surgery for every adolescent withvaricocele is not advisable. Understanding thelimitations in predicting future fertility potential,several reproducible parameters would be helpfulin identifying individuals who would benefit mostfrom treatment. Testicular volume discrepancy ofmore than 20%, as assessed by ultrasonography,is the most common indication for treatment.However, as described in previous sections, sizedifferentials seem to provide the most accurateassessment of impaired fertility to date. Theauthors prefer to follow testicular volume withultrasonography. Still, several studies have showna strong linear relationship between testicularvolume measurements using either Prader orchid-ometer or scrotal ultrasonography.54,81 Although itis recommended that the clinicians use themethod in which they have the most experience,ultrasonography has become the standardmethod and provides a significant benefit overorchidometer in regard to size differentials.

Symptoms such as pain, fullness, or swelling notrelieved by conservative measures may beanother possible indicator for treatment. However,correlation between symptoms and pathology hasnot been evaluated in a controlled manner todate.82 Because it would be difficult to havea normal contralateral testis as a comparison,adolescents with bilateral varicoceles should beconsidered for therapy. For the older adolescent,the physician may discuss the possibility of semenanalysis to aid in decision making. A patient withabnormal semen analysis with high-grade varico-cele, even without testicular hypotrophy, shouldbe considered for treatment.

TREATMENT OPTIONS

The best method for treatment of adolescent vari-cocele has yet to be established. There have beenno randomized, controlled, prospective clinicalstudies that compare the various techniques inadolescents or adults. Treatment options includeopen surgical approaches, laparoscopic varico-cele ligation, and percutaneous transvenousembolization. Several investigators havedescribed innovative minimally invasive surgicalapproaches for the treatment of adolescent vari-cocele, including laparoscopic single-portsurgery83 and robotic-assisted techniques.84

Open Surgery and Arterial Sparing

Open surgery remains the mainstay of varicoceletreatment in adolescents. Based on a review ofthe literature and the results of a survey of pedi-atric urologists in the United States, Paduch andSkoog65 found that high retroperitoneal ligationof the testicular artery and veins (Palomo proce-dure) is the treatment of choice in adolescents.Kass and Marcol85 demonstrated that the classicPalomo repair was associated with a statisticallysignificant decrease in surgical failure ratecompared with artery sparing or inguinal varico-cele ligation. In addition, no patient exhibited testisatrophy after high ligation of internal spermaticartery and vein, which is consistent with findingsby other investigators.86,87

The issue of preserving the testicular artery hasbeen questioned in adults, in whom inadvertentarterial ligation during inguinal dissection for vari-cocele ligation led to poorer postoperative spermquality compared with artery-preserved cohorts.63

Zampieri and colleagues88 compared semen anal-ysis from adolescents with prior laparoscopic var-icocelectomy using either testicular arterypreservation or artery ligation. They showed thatpatients with artery-sparing procedures hadsemen analyses with higher sperm concentration,better motility, increased semen volume, anda higher rate of morphologically normal spermthan those with prior artery ligation.88

Microscopic inguinal or subinguinal approachwith arterial preservation should also be consid-ered as a viable option for adolescent varicoceletreatment. The microsurgical low inguinal or subin-guinal approach has been reported in the adultinfertility literature as the method with the highestsuccess rate (99%) and the lowest morbidity (0%hydrocele). The main potential disadvantage ofthis approach is the need for an operating micro-scope to spare the arteries and lymphatics andthe increased number of veins at this level.

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Laparoscopic and Robotic Varicocelectomy

Laparoscopic varicocelectomy is an appealingoption in that the patient is spared the morbidityof a groin incision. The transabdominal intraperito-neal approach also offers the possibility of bilateralrepair through the same small incisions. There is 1report of a randomized controlled trial of laparo-scopic and open repair that found that the rate ofvaricocele relapse was statistically similar (1.84%vs 1.35%, respectively) between laparoscopicand open varicocelectomy but that the likelihoodof wound complications, scrotal edema, andnecessity of analgesia were all increased signifi-cantly in the open repair group. The laparoscopicgroup also had a decreased length of stay andshorter operative time.89 In terms of varicocelerecurrence, Barroso and colleagues90 recently re-ported a comparison of 1344 patients who under-went open varicocelectomy with 496 patients whounderwent laparoscopic varicocelectomy andnoted that recurrence was seen in 2.9% and4.4%, respectively.

One of the drawbacks to laparoscopic varicoce-lectomy is that the patient traditionally wasrequired to have 3 incisions to facilitate a laparo-scopic camera and 2 working instruments. Linkand colleagues91 described a technique for 2-trocar laparoscopic varicocelectomy, which usestwo 5-mm ports only. After obtaining pneumoper-itoneum with a Veress needle, a 5-mm port wasplaced supraumbilically. A second 5-mm portwas placed in the contralateral lower quadrant.Ten varicoceles in 9 patients were identified andoperated on by using this technique. A harmonicscalpel was used to fulgurate and divide the entirespermatic cord above the inguinal ring. No attemptwas made to spare the testicular artery orlymphatics. At short (6 weeks postoperation)follow-up, there was no evidence of recurrenceor hydrocele.

An evolutionary step forward was also reportedby Kaouk and Palmer83 with their series of single-port laparoscopic varicocelectomy. This procedurewas completed in 3 adolescents using Uni-XSingle Port Access Laparoscopic System (PnavelSystems, Morganville, NJ, USA), a unique 20-mmlaparoscopic port, placed transumbilically. Thisport, in combination with both rigid and articulatinginstruments, allows for single-port laparoscopicvaricocelectomy.

With the advent of the robotic da Vinci SurgicalSystem (Intuitive Surgical, Inc, Sunnyvale, CA,USA), the use of a robotic platform for minimallyinvasive surgery has expanded. Robotic varicoce-lectomy has been reported by 2 groups using 2different techniques. Shu and colleagues84

reported their technique with 8 patients using theda Vinci robot to perform a magnified subinguinalvaricocelectomy, whereas Corcione andcolleagues92 performed a standard transperito-neal bilateral varicocelectomy on 2 patients.

Percutaneous Varicocele Ablation

Transvenous percutaneous varicocele ablationhas the advantages of a quick recovery andminimal pain. The success rate ranges from 89%to 95%, with approximately 6% complications, inaddition to the issue of radiologic exposure ofthe testes. Many urologists reserve this approachfor cases of surgical failure.93

THE FUTURE

The past several years have seen explosive growthin the literature about minimally invasive varicoce-lectomy including laparoscopic, robotic, andpercutaneous techniques. This has enabledsurgeons to offer multiple options to youngpatients to maximize surgical outcomes and mini-mize morbidity.

There is also a great need for further research toimprove selection of patients who may mostbenefit from surgical correction of varicocele.Advanced molecular biology techniques used forthe evaluation of the infertile men have increasedthe understanding of the physiology of spermato-genesis. It is estimated that 13% of men withazoospermia carry microdeletions of the longarm of chromosome Y.94–96 Men with varicoceleand azoospermia or severe oligoasthenospermiamay suffer from point mutation or deletion ofgenes important in spermatogenesis. Y-chromo-some microdeletion analysis is not universallyavailable, and the assay technique has not beenstandardized fully. In the near future, by screeningfor aberrations of genes involved in regulationof spermatogenesis, better criteria for manage-ment of patients with varicocele may beestablished.17,65

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