effects of grade 1 varicocele detected in the pediatric age-group on testicular development

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Effects of grade 1 varicocele detected in the pediatric age-group on testicular development Koji Shiraishi a, , Hiroshi Takihara b , Hideyasu Matsuyama a a Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755-8505, Japan b Department of Urology, Sanyo-Onoda Municipal Hospital, Sanyo-Onoda, Yamaguchi 756-0094, Japan Received 26 November 2008; revised 8 April 2009; accepted 8 April 2009 Key words: Varicocele; Varicocelectomy; Observation; Pediatrics; Adolescent Abstract Purpose: A number of reports have indicated the effectiveness of varicocelectomy on large varicoceles in adolescents. We carried out a 5-year follow-up study to examine the effect of grade 1 varicocele on testicular development. Methods: Of 31 boys with left grade 1 varicocele (mean age, 12.6 years), 10 underwent microsurgical varicocelectomy and 21 were conservatively observed and evaluated for testicular volume and varicocele grade. The control group consisted of 20 healthy age-matched boys without a varicocele. The mean relative left testicular volume was compared with the right testis and the absolute bilateral testicular volumes among the boys in all groups. Results: Of 21 boys who were observed, 13 (62%) continued to have grade 1 varicocele, 4 (19%) developed grade 2 varicocele, and the other 4 boys (19%) showed spontaneous resolution. Twelve testes (57%) developed in parallel with the right testis, and 1 boy (5%) who experienced spontaneous resolution of the varicocele had catch-up testicular growth, whereas 8 boys (38%) had left testicular growth delay with or without an increasing grade of varicocele. Varicocelectomy, but not observation, improved the previously noted testicular growth delay. Furthermore, right testicular growth delay was also noted during observation. Conclusions: More than half of the total number of boys with grade 1 varicocele showed normal development, whereas many boys presented with growth delay in both testes. Thus, we still need to define reliable predictors that will permit selection of the best candidates for varicocelectomy. © 2009 Elsevier Inc. All rights reserved. Several studies have estimated the incidence of varicocele in boys in the pediatric age-group (b15 years) to be up to 20% [1-3], which is similar to the incidence of varicoceles in adults. These findings suggest that the pathophysiologic changes associated with the varicocele presumably starts during childhood. Varicocele is a progressive but surgically correctable condition that results in deterioration of testicular function in the reproductive age. In children and adolescents, testicular growth delay has been the most widely accepted indication for varicocelectomy, and the reversal of testicular size discrepancy or catch-up growth has been observed after the surgery [4-9]. In addition, when left untreated, abnormal spermatogenesis has been found more commonly in adolescents [10,11], and a number of studies in the literature support surgical intervention instead of mere observation. Corresponding author. Tel.: +81 836 22 2275; fax: +81 836 22 2276. E-mail address: [email protected] (K. Shiraishi). www.elsevier.com/locate/jpedsurg 0022-3468/$ see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2009.04.008 Journal of Pediatric Surgery (2009) 44, 19951998

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www.elsevier.com/locate/jpedsurg

Journal of Pediatric Surgery (2009) 44, 1995–1998

Effects of grade 1 varicocele detected in the pediatricage-group on testicular developmentKoji Shiraishi a,⁎, Hiroshi Takihara b, Hideyasu Matsuyamaa

aDepartment of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755-8505, JapanbDepartment of Urology, Sanyo-Onoda Municipal Hospital, Sanyo-Onoda, Yamaguchi 756-0094, Japan

Received 26 November 2008; revised 8 April 2009; accepted 8 April 2009

0d

Key words:Varicocele;Varicocelectomy;Observation;Pediatrics;Adolescent

AbstractPurpose: A number of reports have indicated the effectiveness of varicocelectomy on large varicocelesin adolescents. We carried out a 5-year follow-up study to examine the effect of grade 1 varicocele ontesticular development.Methods: Of 31 boys with left grade 1 varicocele (mean age, 12.6 years), 10 underwent microsurgicalvaricocelectomy and 21 were conservatively observed and evaluated for testicular volume andvaricocele grade. The control group consisted of 20 healthy age-matched boys without a varicocele. Themean relative left testicular volume was compared with the right testis and the absolute bilateraltesticular volumes among the boys in all groups.Results: Of 21 boys who were observed, 13 (62%) continued to have grade 1 varicocele, 4 (19%)developed grade 2 varicocele, and the other 4 boys (19%) showed spontaneous resolution. Twelve testes(57%) developed in parallel with the right testis, and 1 boy (5%) who experienced spontaneousresolution of the varicocele had catch-up testicular growth, whereas 8 boys (38%) had left testiculargrowth delay with or without an increasing grade of varicocele. Varicocelectomy, but not observation,improved the previously noted testicular growth delay. Furthermore, right testicular growth delay wasalso noted during observation.Conclusions: More than half of the total number of boys with grade 1 varicocele showed normaldevelopment, whereas many boys presented with growth delay in both testes. Thus, we still need todefine reliable predictors that will permit selection of the best candidates for varicocelectomy.© 2009 Elsevier Inc. All rights reserved.

Several studies have estimated the incidence of varicocelein boys in the pediatric age-group (b15 years) to be up to20% [1-3], which is similar to the incidence of varicoceles inadults. These findings suggest that the pathophysiologicchanges associated with the varicocele presumably startsduring childhood. Varicocele is a progressive but surgically

⁎ Corresponding author. Tel.: +81 836 22 2275; fax: +81 836 22 2276.E-mail address: [email protected] (K. Shiraishi).

022-3468/$ – see front matter © 2009 Elsevier Inc. All rights reserved.oi:10.1016/j.jpedsurg.2009.04.008

correctable condition that results in deterioration of testicularfunction in the reproductive age. In children and adolescents,testicular growth delay has been the most widely acceptedindication for varicocelectomy, and the reversal of testicularsize discrepancy or catch-up growth has been observed afterthe surgery [4-9]. In addition, when left untreated, abnormalspermatogenesis has been found more commonly inadolescents [10,11], and a number of studies in the literaturesupport surgical intervention instead of mere observation.

1996 K. Shiraishi et al.

Most reports have been focused on large varicoceles (ie,grade 2 and 3); however, the effects of small varicoceles (ie,subclinical and grade 1) on future spermatogenesis isunknown and remains a controversial issue. Furthermore,current guidelines do not recommend interventions for grade1 varicocele in adult patients because of the less than strikingpostoperative improvement of their spermiogram [12,13].Moreover, large varicoceles and grade 1 varicocele thatdevelop during childhood and adolescence might have aharmful effect on future spermatogenesis. Redmon et al [14]reported that the degree of histologic impairment wasindependent of the clinical stage of the varicocele. A numberof boys with grade 1 varicocele showed ipsilateral testiculargrowth delay, and there was no significant difference in theincidence of hypotrophy, categorized by varicocele grade[7,11,15]. In addition, there was also no difference in semenanalysis among the varicocele grades [16]. To our knowl-edge, the effectiveness of varicocelectomy for grade 1varicocele in the pediatric age-group on testicular volumehas not been studied in detail.

Asymptomatic grade 1 varicoceles, without testiculargrowth delay, would remain undiagnosed, which coulddisturb an investigation. Thus, we examined the effect ofgrade 1 varicocele on the testicular development, comparingthe testicular volume with or without varicocelectomy.

1. Patients and methods

A retrospective chart review was conducted in boys withgrade 1 varicocele. We counseled some pediatricians and ourhospital staffs about the purpose of this study and asked themto consult our service if they noted asymmetric sensationbetween left and right spermatic cords on examining theirpatients. The boys were examined in a warm room in supineand standing positions, with and without a Valsalvamaneuver. Varicoceles were classified according to Dubinand Amelar [17] as grade 1 palpable during Valsalvamaneuver, grade 2 palpable without Valsalva maneuver, orgrade 3 visible without the need for palpation. Between 1997and 2004, 35 boys were diagnosed with grade 1 varicocele.Four boys were lost to follow-up and were excluded from thisstudy. A total of 31 boys (range, 9-15 years of age; mean age ±SEM, 12.6 ± 0.4 years) were included in this study. Patientswith right or bilateral varicoceles were also excluded from thestudy. Among the 31 cases, 25 (81%) were asymptomatic,and their condition was detected after physical examinationby the pediatricians or parents, whereas 6 (19%) presentedwith scrotal or left lower abdominal discomfort. Eight (26%)boys presented left testicular growth delay when comparedwith the right testis. Varicocelectomy was performed in 10cases (32%), of which 3 (30%) had both the left testiculargrowth delay and discomfort at presentation, 2 (20%) had lefttesticular growth delay, and 5 (50%) underwent surgery toavoid testicular growth delay, with parents' preference. The

other 21 (68%) cases, including 3 cases with discomfort and 2cases with growth delay, were followed nonoperatively, andthe testicular volume was measured. If varicocelectomy wasperformed, the testicular volume just before the procedurewas noted as final testicular volume. Basically, testicularvolume was evaluated annually in both groups by a singlephysician (KS). Semen analysis was difficult for boysincluded in this study. Testis volume, which has beenshown as a reliable spermatogenic parameter, was used toevaluate the testicular development. Testicular volumemeasurement was carried out using a punched-out orchid-ometer developed by one of the authors (HT) and is readilyapplicable in pediatric urology [7,10]. Sonographicallyderived volume differentials more than 10% between normaland affected testes correlated with a significantly decreasedsperm concentration and total motile sperm count inadolescents with varicocele [16]. If the testicular sizediscrepancy was more than 1 or 2 elliptical rings, signifyingmore than 10% volume differential, on the affected side, thenit was considered as testicular growth delay.Catch-up growthwas defined as testicular volume at least 10% larger than theright testis. All the preoperative examinations and varicoce-lectomies were performed within 2 months after thediagnosis, by a single surgeon (KS), using a microscopeeither after an inguinal or retroperitoneal approach. Nosignificant differences were observed with respect to theprocedure performed [7]. We also included the data oftesticular volume from 20 healthy age-matched boys (mean ±SEM, 12.9 ± 0.6 years at diagnosis and 17.5 ± 0.6 years atfollow-up examination with a mean ± SEM follow-up periodof 4.6 ± 0.5 years) as controls. Color Doppler ultrasono-graphy was performed to rule out subclinical varicocele in allthe boys. This study was approved by the institutional reviewboard of the Saiseikai Shimonoseki General Hospital,Shimonoseki, Yamaguchi, Japan.

Statistical analysis was performed using the paired t testto compare the testicular volumes at diagnosis and follow-up, whereas unpaired t test was used to compare the right andleft testicular volumes. The analysis of variance was used tocompare the results among the control, observation, andvaricocelectomy groups. The values were presented as themean ± SEM. A P value of less than .05 was considered asstatistically significant.

2. Results

Table 1 shows the patients' characteristics in each group.In accordance with the results reported by Greenfield et al [8]showing the age distribution of varicocele in the pediatricage-group, the mean ± SEM age in both the groups of ourstudywere 13.0 years (range, 10-15) and 12.5 years (range, 9-15), respectively. Five boys (16%) and 30 boys (94%)showed Tanner stage 5 at diagnosis and at follow-up,respectively. No difference was observed in Tanner's pubertal

Table 3 Right and left testicular volumes at diagnosis andfollow-up (mL)

At diagnosis At follow-up

Control (n = 20)Right 11.5 ± 0.7 19.3 ± 1.2 ⁎

Left 11.4 ± 0.7 19.2 ± 1.1 ⁎

Observation (n = 21)Right 11.1 ± 0.6 16.9 ± 0.4⁎,†

Left 10.7 ± 0.7 15.1 ± 1.0⁎,†,‡

Varicocelectomy (n = 10)Right 10.9 ± 1.0 19.2 ± 1.2 ⁎

Left 10.3 ± 0.9 19.8 ± 1.4 ⁎

Data are expressed as mean ± SEM.⁎ P b .001 compared to the value at diagnosis (paired t test).† P b .01 among the groups (analysis of variance).‡ P b .05 compared to right testis (unpaired t test).

Table 1 Characteristics of the patients with grade 1 varicocele

Varicocelectomy(n = 10)

Observation(n = 21)

P a

Age at diagnosis 13.0 ± 0.6 12.5 ± 0.4 .50Age at latest follow-upvisit

18.4 ± 0.6 17.2 ± 0.4 .12

Mean follow-up period 5.5 ± 0.3 4.8 ± 0.3 .15FSH (mIU/mL) 3.3 ± 0.4 3.8 ± 0.3 .54LH (mIU/mL) 2.2 ± 0.3 2.1 ± 0.2 .79Testosterone (ng/mL) 1.8 ± 0.6 1.6 ± 0.3 .81

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH),and testosterone are included in the data at diagnosis.

a Unpaired t test.

1997Grade 1 varicocele and the testicular development

grading between the groups (data not shown). The mean ±SEM (range) follow-up periods for the groups were 5.5 ± 0.3(4-7) and 4.8 ± 0.3 (2-7) years, respectively. There were nosignificant differences in the patients' age at diagnosis,follow-up period, and hormonal parameters (Table 1). Also,no varicocelectomy-associated complication was observed,including hematoma, infection, testicular atrophy, or varico-cele recurrence, during the follow-up period.

Of 21 boys who were observed, 13 (62%) continuedhaving grade 1 varicocele on follow-up. However, 4 cases(19%) developed a grade 2 varicocele, whereas the other 4cases (19%) had spontaneous resolution of the varicocele.There was no change in symptoms. Of the 21 testes, 12(57%) testes developed in parallel with the right testis. Onepatient (5%), who experienced spontaneous resolution ofthe varicocele, had catch-up growth. Eight cases (38%) hadleft testicular growth delay with (2 boys) or without (6boys) an increasing grade of varicocele. The mean ± SEMduration to cause the growth delay was 4.2 ± 0.4 years. Fivepatients underwent varicocelectomy when the growth delaywas noted.

At diagnosis, there is no significant difference in the lefttesticular volume when compared with the right (Table 2).During follow-up, left testicular growth failure was noted inthe observation group (P b .01; Table 2). On the other hand,significant left testicular growth was observed in varicoce-lectomy group (P b .01; Table 2). Catch-up growth was notedin 30% of the patients (3/10) in the varicocelectomy group.One patient (5%) had catch-up growth in the control andobservation group, respectively.

Table 2 Left testicular volume compared to right testis atdiagnosis and follow-up (%)

At diagnosis At follow-up

Control (n = 20) 99.1 ± 1.9 99.5 ± 2.0Observation (n = 21) 96.4 ± 2.6 89.3 ± 3.0⁎,†

Varicocelectomy (n = 10) 94.4 ± 4.0 103.1 ± 2.9 ⁎

Data are expressed as mean ± SEM.⁎ P b .01 compared to the value at diagnosis (paired t test).† P b .01 among the groups (analysis of variance).

Ipsilateral growth delay was determined by comparing theleft testicular volume with the right. The left testiculargrowth delay might be underestimated because the leftvaricocele affects both testes. Table 3 shows the bilateraltesticular volumes at diagnosis and follow-up. Both testes inall the groups significantly developed during the follow-upperiod (P b .001; Table 3). In the observation group, the rightand the left testicular volume was significantly smaller thanthat in the other groups (P b .01; Table 3).

3. Discussion

Marked testicular catch-up growth was observed inpatients between 11 and 13 years of age after varicoce-lectomy [2], indicating that the effect of varicocele wasexaggerated during the specific period of pubertal develop-ment for clinically significant testicular growth delay. Witha longer follow-up period, we showed that grade 1varicocele caused testicular growth delay, if left untreated.It is not yet clear whether testicular development aftervaricocelectomy in children and adolescents would have apositive effect on the testicular function [10]. Largevaricoceles are presumed to be more injurious to the testisand are potentially more likely to impair the testicularfunction, implying the need to correct this conditionprophylactically. The recent report by Diamond et al [16],stating that a testicular volume differential more than 10%correlated with a significantly lower sperm concentration, isclinically important for future paternity considerations.Subclinical varicocele is considered a risk factor for thedevelopment of clinically evident varicocele [3]; grade 1varicocele in the pediatric age-group may have a potential toimpair spermatogenesis. A larger prospective investigationwill clarify whether grade 1 varicocele should be treated aswell as large varicoceles for which many investigatorsrecommend early intervention [4-6,10,18,19].

1998 K. Shiraishi et al.

Although there is no evidence for the clinical signifi-cance of small varicoceles in the pediatric age-group, we,along with others, have shown that the proportion ofchildren with left grade 1 or subclinical varicoceleprogressing to a clinically detectable form was 19% and28% [3], respectively. We have shown that 38% of testesshowed growth failure with or without the development ofvaricocele during the 60 months of follow-up. Hence, it isvery likely that long-term exposure to grade 1 varicocelemight have a harmful effect on spermatogenesis. Thesefindings support the concept that grade 1 varicocele is alsoa progressive condition in some patients. Furthermore,unilateral testicular hypotrophy does not usually improve inadulthood [7,18]. On the other hand, we had concernsabout avoiding unnecessary surgery on many of these boysbecause 62% of the patients showed no asymmetricaltesticular development. Along with other researchers, wedemonstrated that the proportion of children with left grade1 or subclinical varicocele that spontaneously resolved was19% and 6% [3], respectively. Furthermore, catch-upgrowth was observed in patients in whom the varicocelewas observed [20], affirming the “wait and watch” policy[12,13]. In addition, correction of all adolescent varicocelesexposes many patients to the risk of anesthesia, and thesurgical outcome is not entirely clear, and because most ofthe small varicoceles are asymptomatic and many aredetected only on routine physical examination, most parentsare not inclined toward surgical intervention. Patientsshould be observed with annual testicular volume measure-ment and/or semen analysis to detect the earliest signs ofvaricocele-related testicular injury. Also, identifying reliablepredictors would be ideal for selecting the best candidatefor surgical management.

On the basis of the reports of testicular histopathologicexamination and volume measurement, we can concludethat a varicocele can affect not only the ipsilateral testis butalso the contralateral right testis [4,10]. Because the righttestis is often used as the “normal reference” for comparingthe volume of the clinically significant left, bilateraltesticular growth delay could lead to an underestimationof varicocele effect in a given patient because the varicoceledisturbs bilateral testicular development. More important,these patients with bilateral testicular volume loss may be ata greater risk of infertility than patients with only lefttesticular volume loss. An unrecognized, smaller right testismight lead the physician to erroneously conclude that thevolume of the left testicle is normal. Ideally, developing areliable growth curve of the testes for healthy boys iswarranted to adequately monitor the testicular developmentin the pediatric age-group.

Apparently, semen parameters and a larger number ofpatients are needed to conclude whether grade 1varicocele should be treated in the pediatric age-group.Prospective studies are necessary to accurately select

patients with grade 1 varicocele, who would benefit mostfrom varicocelectomy.

Acknowledgment

We thank Dr Yoriaki Kamiryo to provide a chance toperform this study at Saiseikai Shimonoseki General Hospital.

References

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