Natural history and long-term testicular growth of acquired undescended testis after spontaneous descent or pubertal orchidopexy

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1 Chapter 4.1 Natural history and long-term testicular growth of acquired undescended testis after spontaneous descent or pubertal orchidopexy WWM Hack LM van der Voort-Doedens J Goede JM van Dijk RW Meijer K Sijstermans BJU Int 2010; 106:

2 Chapter 4.1 Abstract Objective To assess prospectively the natural history and long-term testicular growth of acquired undescended testis (UDT) after spontaneous descent or pubertal orchidopexy in case of nondescent. Patients and methods From 1996 until 2008, 391 boys with 464 acquired undescended testes were included in the study. In accordance with Dutch consensus on nonscrotal testis, spontaneous descent at puberty was awaited; if this did not take place, orchidopexy was performed at puberty. Acquired UDT was defined as a testis previously residing in the scrotum that can no longer be manipulated into a stable scrotal (high scrotal) or nonscrotal (inguinal, impalpable) position. After referral, testis position, testis volume, and puberty stage was monitored annually until adolescence. Testis volume was assessed using an orchidometer and compared with the Dutch standard. All investigations were carried out by the same physician (W.H.). Of these boys, 84 (mean age 12.9 years, range 6.4 to 21.3) were also clinically assessed by a second physician (J.G.), unaware of the results of the first examination. In addition, these boys were assessed with testicular ultrasonography, carried out by both physicians. Results Currently, the mean (range) follow-up is 4.7 (0.1 to 12.0) years, and 253 acquired UDT have reached the scrotum. In 196 of these 253 cases (77.5%) there was spontaneous descent at puberty (mean age at descent 12.9 years, range 9.8 to 16.9); in the other 57 cases (22.5%), pubertal orchidopexy was performed due to nondescent; five cases required orchidectomy. Of the 494 testis volume measurements after spontaneous descent, 458 (92.7%) were at 10 th centile for age of which 311 (63.0%) were 50 th centile, and 107 (21.7%) 90 th centile. After pubertal orchidopexy for nondescent, of the 85 measurements 79 (92.9%) were at 10 th centile, 53 (62.4%) 50 th centile, and 12 (14.1%) 90 th centile. In unilateral cases, after spontaneous descent 174 of the 294 (59.2%) retained testes were found to be smaller than their counterpart and 90 of 294 (30.6%) were equal in size. After pubertal orchidopexy in unilateral cases, 40 of the 51 (78.4%) testes were smaller, and nine (17.6%) were equal in size. There was a strong correlation between both investigators for the measurement of testicular volume by orchidometer, and for the main investigator (W.H.) between his measurements by ultrasound and Prader orchidometer. 148

3 Natural history and long-term testicular growth of acquired undescended testis Conclusion Acquired UDT has a 77.5% tendency of spontaneous descent at puberty. In nearly all cases, after spontaneous descent as well as after pubertal orchidopexy, long-term testicular growth is within the normal range. Introduction Undescended testis (UDT) is one of the most common urological anomalies in boys, and is associated with impaired spermatogenesis and an enhanced risk of testicular cancer. At present, UDT is categorized into congenital and acquired forms. 1,2 It is estimated that congenital UDT is present in % of boys at 1 year old, and acquired UDT in 1.5% of prepubertal boys. Based on histopathological studies, surgical treatment of congenital UDT is now recommended for patients as young as 6 months. 3 By contrast, there is much uncertainty as to the management of acquired cryptorchidism. Usually, at the time of diagnosis the testis is routinely brought down into the scrotum by surgery. 4 It is estimated that as many as 50-60% of all orchidopexies performed worldwide are accounted for by surgery on acquired cryptorchidism. However, so far no long-term longitudinal studies justifying this policy have been reported. Conversely, two studies from the Netherlands have reported spontaneous pubertal descent in 57-71% of the cases, thus reserving pubertal orchidopexy for cases of nondescent. 5,6 In this article, we report the natural history and long-term testicular growth of acquired UDT after spontaneous descent or after pubertal orchidopexy in case of nondescent. These data may be helpful in determining whether a wait and see policy towards acquired cryptorchidism, which is customary in the Netherlands, can be a useful alternative to the prepubertal orchidopexy. Patients and methods In the early 1990s, acquired cryptorchidism was gradually recognised as a separate disorder at our hospital, and prepubertal surgical intervention was withheld in accordance with the Dutch consensus on nonscrotal testis. 7 Subsequently, we started to assess these boys annually for testis position, volume and puberty stage. In the late 1990s, the boys were monitored more closely and, in recent years, a separate questionnaire was introduced. During the entire period, the boys were examined at the outpatient department by the same physician (W.H.). Preliminary results of this ongoing survey were published earlier. 6,8 149

4 Chapter 4.1 Figure 1 Local status stamp as used in this survey during each visit. Testis position was documented with the patient supine (1) and cross-legged (2). Puberty stage was assessed according to Tanner s criteria. Schematic drawing for retractile testis (A, right), high scrotal testis (A, left), inguinal testis (B, right) and impalpable testis (B, left). A B ?? right.... ml* 2 2 left.... ml* right.... ml* left.... ml* puberty P.. G.. puberty P.. G.. * orchidometer * orchidometer A UDT was defined as a testis which could not be brought into a stable scrotal position and for which further traction on cord structures was painful. A retractile testis was defined as a testis which could be brought into a low stable scrotal position, where it remained after release of the testis. If subsequently the cremasteric reflex was triggered, the testis would withdraw to the groin region. A congenital UDT was defined as a UDT which had never been scrotal, whereas an acquired UDT had at some point been fully descended. Each boy referred for nonscrotal testis was enrolled in this study. A separate questionnaire was used to inquire about general health, birth weight and gestational age, urogenital anomalies, medication, ethnic background of the parents, previous groin surgery and major surgical interventions. Adenotonsillectomy and middle-ear drainage were not taken into account. After referral the patients had a general physical examination. The testes were examined using a two-handed technique with the boy supine and squatting. Puberty stage was determined according to Tanner s criteria. Testicular volume was assessed using the Prader orchidometer with volumes ranging from 1 to 25 ml; these volumes were then compared to the Dutch standard. 9 Data on previous testicular position were obtained from the Youth Health Care Institution Hollands Noorden. Due to the Dutch consensus on nonscrotale testis (1986), testis position is meticulously documented, especially in the early years of life by Youth Health Care physicians as part of the routine care. The number of physicians involved throughout the years is unknown. Other information sources of previous testicular position (family doctor, paediatrician, other specialists) were not used. 150

5 Natural history and long-term testicular growth of acquired undescended testis If a retractile testis was diagnosed the boy was monitored annually or biannually and active treatment was not instituted. If a congenital UDT was diagnosed, the boy was referred for orchidopexy. If acquired cryptorchidism was diagnosed the boy was examined annually for spontaneous testicular descent at puberty. If descent did not take place, pubertal orchidopexy was performed. Criteria for orchidopexy were nondescent at puberty stage G 3, with testicular volume of ml as measured by orchidometry. After spontaneous descent or pubertal orchidopexy, the annual follow-up examinations were continued. In cases of orchidopexy, examinations restarted 6 months after surgery. Follow-up was considered complete if the boy was lost for further follow-up (e.g. due to migration or prepubertal surgery at another hospital), if testis volume was identical between follow-up controls, or if the boy had reached the age of 21 years. At each visit, testis position, testis volume and puberty stage were recorded in the medical file, using a local status stamp as shown in Fig. 1. Testis position was recorded with the boy both supine and cross-legged, and the testis was classified as descended, retractile, high scrotal, inguinal or impalpable. For each boy, data were entered into a database, including date of referral, age at referral, diagnosis, side of UDT and follow-up data. In addition, the data from the separate questionnaire were registered. In 84 boys (mean age 12.9 years, range ), a second physician (J.G.) conducted an additional clinical assessment, unaware of the results of the first. Both physicians also performed testicular ultrasonography (US) in these boys. For US we used a highresolution scanner (Auto Image, Falco Software Co., Tomsk, Russia; with a 12 MHz linear array transducer). Testes were scanned in axial and longitudinal planes. Testicular volume was calculated using the approximation for a prolate ellipsoid: length x width x height x π/6 ml. Each boy was measured three times and the highest value was taken as the volumemeasurement. Parenchymal disturbances were not studied and Doppler flow studies to assess testicular blood flow were not undertaken. Correlations between volume measurements were calculated with the Pearson correlation coefficient. The Mann-Whitney test was used to calculate the differences in age at referral (for acquired vs congenital cryptorchidism and for high scrotal vs inguinal testis position) as well as for the differences in testis volume for high scrotal vs inguinal position at spontaneous descent. The differences between uni- and bilateral UDT in acquired vs congenital cryptorchidism were assessed by the chi-squared test, as were differences between high scrotal and inguinal testis position before spontaneous descent vs orchidopexy. 151

6 Chapter 4.1 Results Since 1996, all 734 boys with 932 nonscrotal testes were referred to the outpatient department (Fig. 2). At the time of referral, the mean (median, range) age of the patients was 7.3 (7.6, ) years. The distribution of referrals over the years of the study is given in Table 1. To date, 391 patients with 464 acquired UDT have been inducted in this survey and the mean (range) follow-up is 4.7 ( ) years. Additional clinical data were recorded for 299 boys with acquired cryptorchidism. Of these, 179 (59.9%) had no clinically significant pathology by history, 42 (14.0%) had asthma and 58 (19.4%) had a history of allergies. Other medical problems included chromosomal abnormalities (seven; 2.3%), attention-deficit disorders (21; 7.0%), development disorders (21; 7.0%), endocrine disorders (13; 4.3%), and congenital anomalies (16; 5.6%). Seven boys had urinary tract abnormalities (2.3%), 13 (4.3%) had been circumcised and eight (2.7%) had had hypospadias. Of the 299 boys, 271 (90.6%) had been born after full- term pregnancy and 28 (9.4%) prematurely. In 284 boys (95.0%), birth weight had been normal, whereas 15 boys (5.0%) had had an inappropriate birth weight for their gestational age. The ethnic background was Caucasian for 279 boys (93.3%), Turkish for three (1.0%), North African for 12 (4.0%), and Asian for five (1.7%). Of the 299 boys with acquired UDT, 16 (5.4%) had had groin surgery for inguinal hernia on the same side as the UDT and 13 (4.3%) on the opposite side. Thirteen boys (4.3%) had had previous surgery for congenital UDT on the same side and 13 (4.3%) on the opposite side. Figure 2 A flow chart of the number of boys enrolled in this survey and outcome. Referrals: 734 boys (testes: 932) Retractile testes: 165 boys (testes: 269) Undescended testes: 569 boys (testes: 663) Congenital UDT: 160 boys (testes:177) Acquired UDT: 391 boys (testes: 464) Not classified UDT: 18 boys (testes: 22) 152

7 Natural history and long-term testicular growth of acquired undescended testis Table 1 Number of boys referred annually to the outpatient department for non-scrotal testis during the period of survey ( ). Retractile Undescended testis Year testis congenital acquired unclassified Total * * * Total * In 2002 and 2003 a study on the prevalence of undescended testis was performed in close collaboration with the Youth Health Care Institution in the region, which resulted in an increased number of referrals. At the end of 2007 a study was started to obtain ultrasonographically normative values for testicular volume in healthy boys. In 165 (22.5%) of the total of 734 boys, a retractile testis was diagnosed (mean age years) and in 569 boys (77.5%), UDT was diagnosed. In 40 (8.7%) of the 461 boys with unilateral congenital or acquired cryptorchidism, the opposite testis was diagnosed as retractile. In 160 (28.1%) of the 569 boys diagnosed with UDT, the UDT was congenital and subsequently they underwent orchidopexy. In 391 (68.7%) of the 569 boys, the UDT was acquired. In 18 (3.2%) of the 569 boys with UDT, previous testicular positions could not be obtained and therefore the UDT could not be classified as either congenital or acquired. The mean (range) age at referral for congenital UDT was 2.4 ( ) years and for acquired cryptorchidism was 9.3 ( ) years; this difference was statistically significant (P < 0.001; Mann-Whitney test). 153

8 Chapter 4.1 Figure 3 A flow chart of the number of acquired UDTs included in this survey with outcome and testicular position at referral and during follow-up (ORP, orchidopexy). Prepubertal ORP (n=17) Lost for followup (n=11) Remain high srotal: (n=116) Acquired UDT (n= 464) Secundair Acquired UDT (n=18) Scrotal position (n=253) No scrotal position; still in follow-up (n=165) Spontaneous descent (n=196) Pubertal ORP (n= 57) Initially high scrotal position (n=138) Initially groin region/ impalpable (n= 58) Initially high scrotal position (n=29) Initially groin region/impalpa ble (n= 28) To groin region/impalpa ble (n= 22) Remain high srotal: (n=13) To groin region/impalpa ble (n=16) In 17 (10.6%) of the 160 boys diagnosed with congenital UDT, the anomaly was bilateral and in 143 (89.4%) it was unilateral. Of these 143 boys, the anomaly was on the left in 74 (51.7%) and on the right in the remaining 69 (48.3%). Of the 391 cases of acquired cryptorchidism, the anomaly was bilateral in 73 boys (18.7%) and unilateral in 318 (81.3%). Of these 318 boys, the anomaly was on the left in 133 boys (41.8%) and on the right in the remaining 185 (58.2%). The difference in uni- and bilateral cryptorchidism between congenital and acquired cryptorchidism was statistically significant (P = 0.009; chi-squared test). Of the 464 cases of acquired UDT in 391 boys, in 41 (8.8%) a previous scrotal position was documented at least once, in 41 (8.8%) at least twice, in 69 (14.9%) at least three times and in the remaining 313 (67.5%) cases more than three times. As shown in Fig. 3, in 17 (3.7%) of the 464 cases of acquired cryptorchidism, prepubertal orchidopexy was performed (at another hospital: three; concomitant hydrocele and/or inguinal hernia on five; torsion of the appendix testis in one 1; other reasons in eight). Eleven (2.4%) of the 464 cases were lost for follow-up (it is unknown whether the testis is now scrotal), and 18 (3.9%) (in 13 boys) were initially diagnosed with congenital cryptorchidism but later with secondary acquired cryptorchidism. 154

9 Natural history and long-term testicular growth of acquired undescended testis Acquired cryptorchidism after orchidopexy was excluded in the analysis of natural course and testicular measurements, whereas acquired cryptorchidism secondary to hernia repair was only excluded for testicular measurements. At referral, 302 (65.1%) of the 464 testes were high scrotal, 139 (30.0%) were inguinal, and 23 (5.0%) were impalpable. The mean (range) age at referral of the high scrotal testes was 9.1 ( ) years and of the inguinal and impalpable testes 9.6 ( ) years; this difference was statistically significant (P = 0.039; Mann-Whitney test). At present, 253 testes have reached a scrotal position. In 196 (77.5%) of these cases, the acquired UDT descended spontaneously and in 57 (22.5%) pubertal orchidopexy was required for nondescent. The mean age at spontaneous descent was 12.9 ( ) years and at pubertal orchidopexy 14.3 ( ) years. Five boys had an orchidectomy, all with unilateral UDT (mean age 14.3 years, range ). In three cases this was due to an atrophic testis (one of these might have been congenital), one for an inadequate length of the funiculus making scrotal placement impossible) and one for agenesis of the testis. Of the 196 cases of acquired cryptorchidism which descended spontaneously, 138 (70.4%) were initially high scrotal, whereas 58 (29.6%) were inguinal or impalpable. Of these 138 initially high scrotal testes, 22 (15.9%) cases became inguinal or impalpable during the follow-up. Of the 57 cases of acquired cryptorchidism that were surgically treated at puberty due to nondescent, 29 (50.9%) were initially high scrotal and 28 (49.1%) were initially inguinal or impalpable. During follow-up, 16 (55.2%) of the 29 initially high scrotal testes became inguinal or impalpable. Of the 167 initially high scrotal acquired UDT, 138 (82.6%) descended spontaneously, whereas of the 86 initially inguinal/impalpable acquired UDT, 58 (67.4%) descended spontaneously, which was statistically significant (P = 0.006; chi-squared test). Of the final 129 high scrotal acquired UDT, 116 (89.9%) descended spontaneously, whereas in 13 cases (10.1%), orchidopexy was required. From the final 124 inguinal/impalpable acquired UDT, 80 (64.5%) descended spontaneously and in 44 cases (35.5%), orchidopexy was required (P < 0.001; chi-squared test). The mean age at spontaneous descent was 12.9 ( ) years and at pubertal orchidopexy was 14.3 ( ) years. The mean volume at spontaneous descent was 5.9 (2-25) ml and at pubertal orchidopexy 13.5 (5-22) ml. The mean volume at spontaneous descent was 6.6 ( ) ml for inguinal testes and 5.5 (2-25) ml for high scrotal testes (P = 0.002; Mann-Whitney test). 155

10 Chapter 4.1 A testis volume (ml) B testis volume (ml) Age No. of testes Mean Std Dev ,6 1, ,5 2, ,0 4, ,5 4, ,2 5, ,9 6, ,4 5, ,9 4, ,9 5, ,6 4, ,9 4, ,5 4, ,0. P90 P Age No of testes Mean Std Dev , ,0 2, ,0 5, ,8 3, ,2 4, ,5 4, ,1 6, ,3 2, ,1 3, ,0 1, ,3 2, , ,0. P90 P50 15 P10 15 P C age (years) testis volume (ml) 35 Formally undescended testis after spontaneous descent Formally undescended testis after midpubertal orchidopexy Descended testis (from birth) Descended testis (from birth) D testis volume (ml) age (years) Formally undescended testis after midpubertal orchidopexy Descended testis (from birth) P90 25 P90 P50 P P10 15 P age (years) age (years) 156

11 Natural history and long-term testicular growth of acquired undescended testis Figure 4 Testicular volume in boys with acquired cryptorchidism: a, after spontaneous descent at puberty according to age, measured by comparative palpation with the Prader orchidometer; b, after orchidopexy at puberty due to nondescent according to age, measured by comparative palpation with the Prader orchidometer; c, after spontaneous descent at puberty according to age compared to its counterpart, measured by comparative palpation with the Prader orchidometer; d, after orchidopexy at puberty due to nondescent according to age compared to its counterpart, measured by comparative palpation with the Prader orchidometer. In all plots, reference curves for mean testicular volume according to Mul et al. 9 ; P 10, P 50 and P 90 indicate 10 th, 50 th and 90 th centiles, respectively. In A D, boys with congenital UDT of the opposite side, or chromosomal abnormalities, e.g. Klinefelter syndrome, were excluded. Long-term testicular volume growth according to age after spontaneous descent is shown in Fig. 4a and after pubertal orchidopexy for nondescent in Figure 4b. In these analyses secondary acquired UDT were not taken into account. Of the 494 testis volume measurements after spontaneous descent, 458 (92.7%) were the 10 th centile for age, 311 (63.0%) 50 th centile, and 107 (21.7%) 90 th centile. After pubertal orchidopexy for nondescent, of the 85 measurements 79 (92.9%) were the 10 th centile, 53 (62.4%) 50 th centile and 12 (14.1%) 90 th centile. The volume of the cryptorchid testis in unilateral cases is shown in comparison to its counterpart after spontaneous descent in Fig. 4c and after pubertal orchidopexy in Fig. 4d. The mean volume of the UDT after spontaneous descent was 12.6 (range 3-28) ml, vs 15.4 (3-30) ml for its counterpart (P < 0,001) and after pubertal orchidopexy 16.1 (3-28) and 21.9 (10-30) ml, respectively (P < 0,001). It was calculated that after spontaneous descent 174 (59.2%) of the 294 retained testes were smaller than their counterparts and 90 (30.6%) of the 294 were of equal size. After pubertal orchidopexy 40 (78.4%) of the 51 testes were smaller than their counterparts and nine (17.6%) of the 51 testes were equal. Table 2 shows the mean volume of the testis after spontaneous descent and after pubertal orchidopexy for high scrotal and inguinal UDT for each age group. There was no statistically significant difference between the groups. There was a weak correlation between the volume of the testis after spontaneous descent or after pubertal orchidopexy and the age at referral (r = and 0.309, respectively) and between the volume of the testis after spontaneous descent or after pubertal orchidopexy and the duration of nondescent (r = and 0.275, respectively). Previous groin surgery had been performed on the same side in three (1.5%) of the 196 spontaneously descended testes and in three (5.3%) of the 57 testes in which pubertal orchidopexy was performed (P = 0.130; Fisher s exact test). 157

12 Chapter 4.1 Table 2 Mean testicular volume (measured by orchidometer) after spontaneous descent or pubertal orchidopexy according to age for initially high scrotal and inguinal acquired cryptorchidism. Initial testis position High scrotal Groin region Age, years n testes Mean (SD) n testes Mean (SD) P value After spontaneous descent (1.1) (2.6) (2.1) ns (4.5) (3.3) ns (4.6) (4.1) ns (6.2) (4.9) ns (6.6) (5.8) ns (6.2) (4.5) ns (4.4) (4.1) ns (5.6) (1.8) (5.7) (3.8) (4.6) (3.5) (4.9) (0.0) After pubertal orchidopexy (2.3) (2.1) (6.8) (2.1) (3.0) (3.7) (4.0) (5.4) (2.8) (8.7) (5.6) (2.9) (2.6) (2.5) (3.5) ns = not significant; - = too few values 158

13 Natural history and long-term testicular growth of acquired undescended testis Table 3 Comparison of measurement of testis volume for two age groups ( 12 and > 12 years) by Prader orchidometer and US between two investigators (W.H., J.G.) and comparison of both methods in one investigator (W.H.) Measurement of testes correlation between correlation between testis volume (n) both investigators # ultrasound and orchidometer # orchidometer 12 years > 12 years ultrasound 12 years > 12 years investigator WH 12 years > 12 years # Pearson s rank correlation In 84 boys (mean age 12.9 years; range ), testis position and volume was determined by two independent investigators (W.H. and J.G.) by orchidometry and using US. Both investigators were unaware of each other s results. To avoid bias, the orchidometer was used first, followed by US. Table 3 shows the correlation between both investigators for volume measurement by orchidometer and US according to age (< 12 and > 12 years). In addition, it shows the correlation of testis volume measurement by orchidometer and US as measured by W.H. Discussion This series shows spontaneous descent of acquired cryptorchidism in 77.5% of the cases. After spontaneous descent and after pubertal orchidopexy, long-term testicular growth is within the normal range in nearly all cases. Acquired cryptorchidism is mainly seen after the age of 4-5 years, but early forms have also been recognised. 10 Causal factors include failure of natural growth of the spermatic cord due to a fibrous remnant of the processus vaginalis 11, groin surgery, an increased cremasteric tone as part of a more generalised muscle hypertonicity, peritesticular adhesions fixing the testis in an inguinal position, and genitofemoral nerve dysfunction. The acquired anomaly has also been suggested to be a low-lying type of congenital UDT 159

14 Chapter 4.1 that is difficult to diagnose early in life 12 or to be the result of observer error. Retractile testes seem prone to develop acquired cryptorchidism. 13 For congenital UDT, orchidopexy is currently recommended at 6-12 months of age in order to preserve testicular germ cell maturation. 14 Early orchidopexy seem to be beneficial for long-term testicular growth of congenital UDT. 15 By contrast, there is much controversy about the management of acquired cryptorchidism, mainly due to a nearly total lack of longitudinal follow-up data. Prompt surgical correction at the time of diagnosis is usually routinely recommended. 16,17 This is mainly based on an expected negative effect of the inguinal thermal environment on testicular development. However, in this series, after spontaneous descent, 92.7%, and after pubertal orchidopexy, 93% of the testis volume measurements were 10 th centile for age. These data do not seem to indicate a negative inguinal environment effect on testicular growth. Moreover, the frequent inguinal position of retractile testes has never been an argument for surgery. Bremholm Rasmussen et al. 18 showed that late spontaneous descent after the age of 10 years in bilateral cryptorchidism might lead to impaired fertility. However, in their study congenital and acquired forms were not distinguished separately. Mayer et al. 19 reported the same histopathological changes in acquired cryptorchidism as in congenital cryptorchidism, which was reconfirmed by Rusnack et al.. 20 Taran et al. 21 recently questioned these findings as 43% of the ascending group had a patent processus vaginalis, which suggests that many of these were primary congenital UDT. It is still unknown whether degenerative histological changes may benefit at all from surgery. Surgery itself may lead to complications such as direct injury to the vas deferens or testicular vessels. 22 Also, undue dissection and corresponding stretching of these structures during and after surgery will result in vascular damage and corresponding parenchymal loss. Repeat surgery may further compress vascular supply. Vascular damage may be more extensive than previously presumed. 23 As far as could be ascertained, no studies have been published reporting long-term testicular growth of acquired UDT after prepubertal orchidopexy. A previous, preliminary study showed that for 101 boys with 122 acquired UDT who had undergone prepubertal orchidopexy, 89 of the 120 operated testes (74.2%) were 50 th centile of which 43 (35.8%) were 10 th centile. 24 For these reasons, Guven et al. 25 recently concluded that surgical intervention might not be warranted since the ascending testis has a high tendency to descend spontaneously during puberty. Moreover, in the UK a decline in orchidopexy was recently reported in boys aged 8-10 years, probably due to increasing awareness of the phenomenon of acquired cryptorchidism. 26 In some countries, e.g. the USA, orchidopexy might be carried out to avoid legal sanctions for leaving the state of nondescent uncorrected. 12 However, in the late 1980s a consensus development conference on nonscrotal testis was held in the Netherlands. 7 It was agreed that testes descended at birth should only be surgically treated if the testes fail to descend at puberty, and testis volume is ml (puberty 160

15 Natural history and long-term testicular growth of acquired undescended testis stage G 3 according to Tanner). We believe that more accurate and individual criteria should be developed for surgery during puberty. These should include age, prepubertal position (high scrotal vs inguinal/impalpable), puberty stage, serial US determination of testicular volume and growth, and perhaps serial hormonal assay. The primary goal of the treatment of cryptorchidism is to achieve normal or at least improved fertility and to prevent testicular germ cell tumour (TGCT). Cryptorchidism leads to a 3-5% risk of TGCT, which is four to seven times more than in the healthy population. It is generally held that orchidopexy does not reduce the risk of cancer but renders the retained testis amenable to self-examination later in life. However, recently the age at which surgery is performed with a threshold of 13 years, was recognized as a risk factor. 27 It remains uncertain whether the risks of infertility and malignancy in acquired cryptorchidism are the same as in congenital cryptorchidism. The risk of cancer in acquired cryptorchidism might be lower than in congenital cryptorchidism as in acquired cryptorchidism, neonatal gonocytes have transformed normally before the abnormality develops. 28 Also, that these testes descended normally and later ascended to the superficial inguinal pouch might mean that they have a more favourable fertility potential. 29 This hypothesis seems to be supported by the results of this survey, showing a nearly normal testicular growth. In this survey, there was, in unilateral UDT after spontaneous descent and after orchidopexy. a significant smaller testis than its counterpart in 59,2% and 78,4%, respectively. In addition, in five cases, all with unilateral UDT, orchidectomy was performed, in three of them for atrophy of the testis. An explanation is not easily offered. A smaller testicle is common in adults who were formerly surgically treated for unilateral UDT. Formerly cryptorchid testes usually reach a volume in the adult of only about a half of that of the contralateral side. Possible causal factors might include primary abnormality resulting in impaired growth of the retained testis and compensatory hypertrophy of its counterpart. The present study has some limitations. Testicular function was evaluated by volume measurement, which is ethically feasible and acceptable in pre-adolescent boys for serial determination. However, testicular volume, as measured by orchidometer or US, is an approximate and indirect measure of spermatogenic activity. 30 For Dutch boys, normative values are only available for orchidometric measurement. In this series, orchidometric and US measurements correlated well. Another potential weakness is that in the early years of this survey patients were not monitored as meticulously as in later years. Moreover, not all patients returned for serial examinations, which was in part due to our initial practice pattern. Both these circumstances might have resulted in incomplete data acquisition. Errors in physical examinations cannot be ruled out, which might have resulted in 161

16 Chapter 4.1 misinterpretations. However, this does not seem to be a major factor because patients were examined throughout the years by the same physician to avoid interobserver variation and to ensure that the boy returned for serial follow-up examinations. In addition, there was a good correlation between the two investigators. Further weaknesses of this series might be that previous testicular positions were obtained from the Youth Health Care Institution, as documented by various Youth Health Care physicians. The accuracy of these data and interobserver variation could not be tested. This might especially have played a role in the cases of orchidectomy. In conclusion, this series shows that acquired cryptorchidism has a high tendency for spontaneous descent at puberty. In addition, in nearly all cases long-term testicular growth was within the normal range both after spontaneous descent and after pubertal orchidopexy. There is a higher tendency for spontaneous descent in high scrotal acquired UDT than in the inguinal or impalpable variant. Testis volume growth does not correlate with prepubertal testis position and correlates only poorly with age at referral and with duration of nondescent. By contrast, the effect of prepubertal orchidopexy on long-term testicular growth of acquired cryptorchidism remains largely enigmatic. Hence, a randomized controlled trial of prepubertal orchidopexy versus natural course should be initiated. Until then, the results of this series so far do not indicate a necessity to change our wait and see policy towards acquired cryptorchidism. 162

17 Natural history and long-term testicular growth of acquired undescended testis References 1. Barthold JS, González R. The epidemiology of congenital cryptorchidism, testicular ascent and orchidopexy. J Urol 2003; 170: Virtanen HE, Toppari J. Epidemiology and pathogenesis of cryptorchidism. Hum Reprod Update 2008; 14: Ritzén M, Bergh A, Bjerknes R, et al. Nordic consensus on treatment of undescended testes. Acta Pediatr 2007; 96: Bonney T, Southwell B, Donnath S, Newgreen D, Hutson J. Orchidopexy trends in the paediatric population of Victoria, J Pediatr Surg 2009; 44: Eijsbouts SW, de Muinck Keizer-Schrama SMPF, Hazebroek FWJ. Further evidence for spontaneous descent of acquired undescended testes. J Urol 2007; 178: Sijstermans K, Hack WWM, van der Voort-Doedens LM, Meijer RW, Haasnoot K. Puberty stage and spontaneous descent of acquired undescended testis: implications for therapy? Int J Androl 2006; 29: De Muinck Keizer-Schrama SMPF. Consensus beleid bij de niet in het scrotum gelegen testis. Ned Tijdschr Geneeskd 1987; 131: Hack WWM, Meijer RW, van der Voort-Doedens LM, Bos SD, Haasnoot K. Natural course of acquired undescended testis in boys. Br J Surg 2003; 90: Mul D, Fredriks AM, van Buuren S, Oostdijk W, Verloove-vanHorick SP, Wit JM. Pubertal development in the Netherlands Pediatr Res 2001; 50: Wohlfahrt-Veje C, Boisen KA, Boas M, et al. Acquired cryptorchidism is frequent in infancy and childhood. Int J Androl 2009; 30: Clarnette TD, Hutson JM. Is the ascending testis actually stationary? Normal elongation of the spermatic cord is prevented by a fibrous remnant of the processus vaginalis. Pediatr Surg Int 1997; 12: Redman JF. The ascending (acquired undescended) testis: a phenomenon? BJU Int 2005; 95: Stec AA, Thomas JC, DeMarco RT, Pope JC, Brock JW, Adams MC. Incidence of testicular ascent in boys with retractile testes. J Urol 2007; 178: Ritzèn M. Treatment of undescended testicles how, when and where? Acta Pediatr 2007; 96: Kollin C, Karpe B, Hesser U, Granholm T, Ritzén EM. Surgical treatment of unilaterally undescended testes: testicular growth after randomization to orchidopexy at age 9 months or 3 years. J Urol 2007; 178:

18 Chapter Bonney T, Hutson J, Southwell B, Newgreen D. Update on congenital versus acquired undescended testes: incidence, diagnosis and management. ANZ J Surg 2008; 78: Taghizadeh AK, Thomas DF. Ascent of the testis revisited: fact not fiction. BJU Int 2008; 102: Bremholm Rasmussen T, Ingerslev HJ, Hostrup H. Bilateral spontaneous descent of the testis after the age of 10: subsequent effects on fertility. Br J Surg 1988; 75: Mayr J, Rune GM, Holas A, Schimpl G, Schmidt B, Haberlik A. Ascent of the testis in children. Eur J Pediatr 1995; 154: Rusnack SL, Wu HY, Huff DS, et al. The ascending testis and the testis undescended since birth share the same histopathology. J Urol 2002; 168: Taran I, Elder JS. Results of orchidopexy for undescended testis. World J Urol 2006; 24: Mouriquand PDE. Undescended testes in children: the paediatric urologist s point of view. Eur J Endocrinol 2008; 159: Suppl 1: S Riebel T, Herrmann C, Wit J, Sellin S. Ultrasonographic late results after surgically treated cryptorchidism. Pediatr Radiol 2000; 30: Meijer RW, Hack WWM, van der Voort-Doedens LM, van der Ploeg T, Bos SD. Adverse effect of orchidopexy on long term testicular growth in acquired undescended testis? In: Acquired undescended testis. Academic thesis. Free University, Amsterdam, the Netherlands. pp , Guven A, Kogan BA. Undescended testis in older boys: further evidence that ascending testes are common. J Pediatr Surg 2008; 43: McCabe JE, Kenny SE. Orchidopexy for undescended testis in England: is it evidence based? J Pediatr Surg 2008: 43: Pettersson A, Richiardi L, Nordonskjold A, Kaijser M, Akre O. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med 2007; 356: Hutson JM, Clarke MCC. Current management of undescended testicle. Semin Pediatr Surg 2007; 16: Murphy F, Paran TS, Puri P. Orchidopexy and its impact on fertility. Pediatr Surg Int 2007; 23: Takihara H, Cosentino MJ, Sakatoku J, Cockett ATK. Significance of testicular size measurement in andrology: II. Correlation of testicular size with testicular function. J Urol 1987; 137:

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