- Email: [email protected]
Contralateral metachronous undescended testis: Is it predictable?
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Journal of Pediatric Urology (2017) xx, 1.e1e1.e5
Contralateral metachronous undescended testis: Is it predictable? Madeline Cancian a, Pamela Ellsworth b, Anthony Caldamone a Summary
possible predictors of subsequent UDT using PROC PHREG with SAS Software 9.4.
a
Department of Urology, Warren Alpert Medical School, Brown University, Providence, RI, USA
b
Division of Urology, Nemours Children’s Hospital, Orlando, FL, USA Correspondence to: M. Cancian, 2 Dudley Street, Suite 174, Providence, RI 02903, USA, Tel.: þ1 207 522 6718; fax: þ1 401 444 6947 [email protected] (M. Cancian) Keywords Undescended testis; Retractile testis; Acquired undescended testis Received 22 November 2016 Accepted 9 March 2017 Available online xxx
Introduction Metachronous undescended testis (mcUDT), an acquired UDT after contralateral orchiopexy, can occur in some boys. If one were able to predict its occurrence, one might consider a proactive approach or at least one would be able to counsel the parents accordingly. Our hypothesis was there may be characteristics evident at the time of initial orchiopexy which could predict the development of contralateral mcUDT. Objective The aim was to Identify factors present at initial orchiopexy that predict development of subsequent mcUDT. Study design Subjects were identified using the Current Procedural Terminology code for inguinal orchiopexy (54640). We included patients from January 1997 to October 2015. We included patients who underwent orchiopexy for unilateral UDT (uUDT). The study population consisted of patients who had undergone metachronous orchiopexies; controls were patients who were 17 years at time of data collection with a single orchiopexy. Cox proportional hazard regression was used to model the relationship between
Table
Results From 1035 eligible patients we identified 38 with mcUDT and 207 controls (uUDT). Median age at the first orchiopexy of mcUDT patients was 2.5 years (min/max, 0.50/10.4 years) and 8.2 years (min/max 0.70/12.8 years) for uUDT, p < 0.0001. Subjects with a contralateral retractile testis on preoperative exam had a 4.2 times higher rate of subsequent UDT than patients with a contralateral descended testis (95% CI 2.077e8.353). The rate of mcUDT was 6.7 times higher if the testis was a retractile testis under anesthesia (95% CI 2.7e16.5) (Table). Discussion Contralateral retractile UDT was a significant predictor of mcUDT. We believe patients with a contralateral retractile testis at time of orchiopexy should be counseled on bilateral orchiopexy. The risks of complications with orchiopexy should be weighed against risks of a subsequent surgery and anesthesia event. Conclusion A discussion of risks and benefits regarding bilateral orchiopexies should be undertaken with the parents prior to surgery in the setting of an UDT with contralateral retractile testis.
Patient characteristics and predictors of mcUDT.
Age at initial orchiopexy, years Congenital, % Contralateral examination in office (% retractile) Contralateral examination under anesthesia (% retractile) Ipsilateral PV open, %
Contralateral UDT (38)
Unilateral UDT (204)
p
2.5 65 52
8.2 52 18
<0.0001 0.10 <0.0001
22
2
<0.0001
48
59
0.14
PV Z processus vaginalis. http://dx.doi.org/10.1016/j.jpurol.2017.03.011 1477-5131/ª 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011
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1.e2
Introduction The incidence of congenital undescended testis (UDT), defined as a testis that has not descended prior to 6 months of age, is stated to be 1% [1]. It is recommended that these boys undergo orchiopexy between 6 and 12 months of age [2]. A significant number of boys undergo orchiopexy after 2 years of age, a phenomenon that is being increasingly recognized as a consequence of acquired UDT and not a missed diagnosis of congenital UDT [3e6]. Acquired UDT is defined as an undescended testis in a boy with a prior documented descended testis on the ipsilateral side. Both types of UDT carry an increased risk of testicular cancer [7] and decreased fertility potential [8]. The exact mechanism of acquired UDT is not understood; however, it is thought to be a variant of congenital UDT [9,10] and thus should carry the same potential sequelae [11]. Although the incidence is unknown, some boys develop metachronous UDT, requiring two separate orchiopexies. Our hypothesis was there may be characteristics evident at the time of initial orchiopexy that might predict the development of contralateral metachronous UDT.
Methods By database query using the Current Procedural Terminology code for inguinal orchiopexy (54640), we identified all patients with UDT between the dates of January 1997 and October 2015. We included all patients who underwent orchiopexy for the indication of UDT. We excluded patients who underwent orchiopexy for a testicular torsion or a contralateral orchiopexy in the finding of an ipsilateral testicular nubbin after inguinal exploration for UDT. We excluded all patients undergoing two-stage FowlereStephens procedures and patients with bilateral UDT at time of presentation. Through retrospective chart review we identified all patients who had undergone bilateral metachronous orchiopexy. Our control group comprised all patients who had undergone unilateral orchiopexy and were 17 years old at the time of data collection. We then collected data on age, type of UDT (congenital vs. acquired), physical examination in the office and under anesthesia, surgical approach, and surgical findings. UDT was considered congenital if present at birth by physician examination or by parental or primary care report, and acquired if the patient had a previously documented descended examination in our system or if a parent reported previous descended status. On examination, the testis was considered descended if it was in the scrotum at the time of examination. A testis was retractile if it could be brought into the scrotum and stayed after fatigue of the cremaster muscle. Physical examinations were identified both during a preoperative office visit and intraoperatively under anesthesia and prior to the start of the procedure. The surgical approach included prescrotal, inguinal, or one-stage laparoscopic orchiopexy. Note was also taken if the Prentiss maneuver was needed. The location of UDT was classified as able to pull into the scrotum but did not stay (prescrotal), superficial pouch, inguinal canal, or non-plapable. Because our center is the only pediatric urology one in the state, it was assumed that patients who had a prior
M. Cancian et al. orchiopexy for UDT would present to the same center if the contralateral testis ascended. With this is mind, we assumed that if a patient did not return, then they did not experience a contralateral UDT. Therefore, we right censored using time until their 17th birthday as “last known follow up” for controls. Seventeen was chosen as a conservative estimation of puberty and thus the point when secondary UDT could no longer occur. As a conservative effort, we removed all cases where first orchiopexy occurred over the age of 13; this was to allow a 4-year window by which a patient could experience a contralateral UDT. Data were collected and managed using REDCap electronic data capture tools hosted at our institution [12]. REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies, providing 1) an intuitive interface for validated data entry; 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for importing data from external sources. Cox proportional hazard regression was used to model the relationship between possible predictors of subsequent UDT using PROC PHREG with SAS Software 9.4. The time until orchidopexy was estimated using PROCLIFETEST.
Ethical approval Institute Review Board approval was obtained through our institution for this study.
Results We identified 1035 patients who were eligible for this study (Fig. 1). Of these patients, 50 had metachronous contralateral UDT (mcUDT) after initial orchiopexy, comprising 4.8% of the total UDT population. Among the remaining 985 patients, we identified 240 patients who were 17 at the time of data collection. We were able to obtain charts for 38 of the patients with mcUDT and 204 of the patients with unilateral UDT (uUDT) (Table 1). Comparing the 38 mcUDT patients with the 204 uUDT patients, the median age at the first orchiopexy of patients who had a subsequent orchiopexy was 2.5 years (min/max 0.50/10.4) and 8.2 years (min/max 70/12.8) for those who did not (p < 0.0001) (Fig. 1). The median time until subsequent orchiopexy in patients who developed a contralateral UDT was 3.5 years (95% CI 2.0e5.0 years). The median time between first orchiopexy and age of 17 for those who did not have a second orchiopexy was 8.9 years (95% CI 8.4e9.8). Contralateral testicular examination was significantly predictive of a subsequent UDT (p < 0.0001). Specifically, subjects who had a retractile testis on preoperative physical examination had a 4.2 times higher rate of subsequent UDT than patients who had a descended testis (95% CI 2.077e8.353). In addition, contralateral intraoperative testicular examination was significantly predictive of a subsequent UDT, p < 0.0001. Specifically, subjects who had a retractile testis under anesthesia had a 6.7 times higher rate of subsequent UDT than patients who had a descended
Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011
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Contralateral metachronous undescended testis
Figure 1
Table 1
1.e3
Inclusion and exclusion criteria.
Summary of patient characteristics.
Age at initial orchiopexy % Congenital Orchiopexy technique
Intraop ipsilateral testicular position
Prescrotal Inguinal Laparoscopic Prentiss Pulls down Superficial pouch Inguinal Nonpalpable
Contralateral exam in office (% retractile) Contralateral exam under anesthesia (% retractile) Ipsilateral PV open
testis (95% CI 2.7e16.5). In the patients who did not go on to have a mcUDT, 18% had a retractile testis in the office and only 2% had a retractile testis under anesthesia. Of note, the testicular examination preoperatively was missing in 3.7% of the population and the examination under anesthesia was missing in 7.5% of the population. No relationship was found for side of initial UDT (p Z 0.4947), acquired versus congenital UDT (p Z 0.40), procedure type (p Z 052), ipsilateral testicular position (p Z 0.71), size of ipsilateral UDT (p Z 0.21), and patency of the processus vaginalis (p Z 0.08).
Discussion Retractile testes, in the absence of contralateral UDT, are known to carry an increased risk of becoming undescended. Agarwal et al. [13] determined that retractile testes have a
mcUDT (38)
uUDT (204)
P value
2.5 yrs 65% 11 18 2 1 10 17 4 3 52% 22% 48%
8.2 yrs 52% 55 114 5 7 40 106 39 17 18% 2% 59%
<0.0001 0.1
<0.0001 <0.0001 0.14
32% chance of becoming undescended, with the risk being higher among boys <7 years old. Other series have shown a lower rate of ascent, from 3.2% to 14% [14,15]. These findings have led to a wait and see approach where the testis is given time to declare itself. Our findings show boys who have a contralateral retractile testis in the setting of a unilateral UDT have a 4e6.7 times increased likelihood of developing a UDT compared with boys with a normally descended contralateral testis. Thus in boys with contralateral retractile testis, especially under anesthesia, it may be worth performing bilateral orchiopexies to avoid a potential orchiopexy in the future. The greater risk of developing an UDT with a retractile testis under anesthesia than a retractile testis in the office examination is likely due to an underlying anatomic abnormality. As a retractile testis is due to a cremasteric reflex [13], boys under general anesthesia should have a decreased or absent cremasteric reflex. Boys who continue to have a
Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011
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1.e4 retractile testis while under anesthesia may have an underlying anatomic abnormality in addition to an active cremasteric muscle, which may contribute to a higher rate of subsequent UDT than in boys whose retractile testis becomes descended under anesthesia. The finding of a retractile testis under anesthesia is not common. It was present in 22% of the mcUDT population and only 2% of the uUDT population. With such a low prevalence in the uUDT population, there would be a low rate of unnecessary contralateral orchiopexies. Unfortunately, it is not understood what causes acquired UDT, so orchiopexy in the setting of a retractile testis cannot be guaranteed to prevent future UDT. Factors that have been hypothesized as contributing to acquired UDT include partial absorption of the processus vaginalis into the parietal peritoneum [16] or a fibrous remnant of the processus vaginalis inhibiting the stretch of the spermatic cord [17]. More recently, there has been enthusiasm for the theory that the spermatic cord is initially long enough for the testis to reach the low scrotum at birth however as the boy grows, a congenitally shortened cord tugs the testis back towards the inguinal canal [9]. At the time of orchiopexy, compared with congenital UDTs, acquired UDTs are typically closer to the scrotum and found in the superficial inguinal pouch, have a closed processus vaginalis, and have a normal attachment of the gubernaculum [18]. These findings support the theory of a shortened spermatic cord, and not a widely patent processus vaginalis or ectopic gubernacular attachment, leading to acquired UDT. Thus orchiopexy with lengthening of the spermatic cord to the internal ring by releasing the restrictive fibers should prevent the retractile testis from becoming undescended. To prove this theory, however, there would need to be a prospective trial. As with any procedure, the risks of preforming bilateral orchiopexy in the setting of a contralateral retractile testis must be weighed against the benefits. Undesirable outcomes following single-stage orchiopexy, including testicular atrophy, long-term pain, and suprascrotal location, are complications following 0.6% of procedures [19]. One must also factor in the extended anesthesia time, which may carry an increased cognitive risk; however, the data suggest an additional anesthesia event is more harmful than an extended event [20,21]. Owing to the nature of this study, we were unable to determine the incidence of metachronous contralateral UDT. However, since orchiopexy carries a low complication rate, consideration should be made for bilateral orchiopexy in patients with a contralateral retractile testis to avoid a second anesthesia and postoperative recovery in the future. There were many limitations to this study. The case and control population displayed significant differences in age at orchiopexy. To ensure the controls had no chance of developing a contralateral UDT, all control patients needed to be post-pubertal at the time of data collection. This consideration skewed our population towards an older age group. Despite the age disparity, there was no statistical difference between the type of UDT (congenital vs. acquired) in the two groups. Additionally, the type of UDT was not found to be predictive of subsequent contralateral UDT. We assumed that none of the control subjects went on to develop a contralateral UDT; however, we cannot be sure of this. This assumption was based on the fact that 1) ours is the
M. Cancian et al. only pediatric urology practice in the state, and 2) patients who had a developed relationship with a pediatric urologist would likely return to the same urologist if a new problem arose. In our practice patients are followed for 6 months after orchiopexy, so it is possible that some controls developed a contralateral UDT and obtained care elsewhere. However, we cannot account for nor control for patient migration. Despite these major limitations, our results show that presence of contralateral retractile testis at time of orchiopexy carries a four to six times odds of developing a contralateral UDT. At the time of orchiopexy, it is worth counseling the patient and family on the risks of developing a subsequent UDT and discussing a possible prophylactic contralateral orchiopexy.
Conclusion Boys who have a contralateral retractile testis at the time of ipsilateral orchiopexy have a four to six times odds ratio of developing a contralateral UDT compared with boys with a normally descended contralateral testis. Consideration should be given to bilateral orchiopexy in this setting or, at the least, these boys and their families should be counseled on the risk of a future surgery.
Conflict of interest None.
Funding None.
Acknowledgment We would like to thank Grayson Baird for his assistance on the statistical analysis and Drs Richard Caesar and Leslie Tackett for the use of their patients in this study.
References [1] Thong M, Lim C, Fatimah H. Undescended testes: incidence in 1002 consecutive male infants and outcome at 1 year of age. Pediatr Surg Int 1998;13:37e41. [2] Kolon TF, Herndon CDA, Baker LA, Baskin LS, Baxter CG, Cheng EY, et al. Evaluation and treatment of cryptorchidism: AUA Guideline 2014. Retrieved November 20, 2016, from https:// www.auanet.org/common/pdf/education/clinical-guidance/ Cryptorchidism.pdf. [3] Hadziselimovic F, Hecker E, Herzog B. The value of testicular biopsy in cryptorchidism. Urol Res 1984;12:171e4. [4] Hutson JM, Goh DW. Can undescended testes be acquired? Lancet 1993;341:504. [5] Toppari J, Kaleva M. Maldescendus testis. Horm Res 1999;51: 261e9. [6] Hack WW, Meijer RW, Van Der Voort-Doedens NM, Bos SD, De Kok ME. Previous testicular position in boys referred for an undescended testis: further explanation of the late orchidopexy enigma? BJU Int 2003;92:293e6. [7] Wood HM, Elder JS. Cryptorchidism and testicular cancer: separating fact from fiction. J Urol 2009;181:452e61.
Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011
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Contralateral metachronous undescended testis [8] Lee PA, O’Leary LA, Songer NJ, Coughlin MT, Bellinger MF, LaPorte RE. Paternity after unilateral cryptorchidism: a controlled study. Pediatrics 1996;98:676e9. [9] Hack WW, Geode J, van der Voort-Doedens LM, Meijer RW. Acquired undescended testis: putting the pieces together. Int J Androl 2012;35:41e5. [10] Rusnack SL, Wu SY, Huff DS, Snyder 3rd HM, Zderic SA, Carr MC, et al. The ascending testis and the testis undescended since birth share the same histopathology. J Urol 2002;168:2590e1. [11] Promm M, Schroder A, Neissner C, Eder F, Rosch WH, Schroder J. Acquired cryptorchidism: more harm than thought? J Pediatr Urol 2016;12. 236.e1e6. [12] Harris Paul A, Taylor Robert, Thielke Robert, Payne Jonathon, Gonzalez Nathaniel, Conde Jose G. Research electronic data capture (REDCap) e a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377e81. [13] Agarwal PK, Diaz M, Elder JS. Retractile testis e is it really a normal variant? J Urol 2006;175:1496e9. [14] Stec AA, Thomas JC, DeMarco RT, Pope 4th JC, Brock 3rd JW, Adams MC. Incidence of testicular ascent in boys with retractile testes. J Urol 2007;178:1722e4.
1.e5 [15] Bae JJ, Kim BS, Chung SK. Long-term outcomes of retractile testis. Korean J Urol 2012;53:649e53. [16] Atwell JD. Ascent of the testis: fact or fiction. Br J Urol 1985; 57:474e7. [17] 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;12:155e7. [18] Meijer RW, Hack WW, van der Voort-Doedens K, Haasnoot K, Bos SD. Surgical findings in acquired undescended testis. J Pediatr Surg 2004;39:1242e4. [19] Kozminski DJ, Kraft KH, Bloom DA. Orchiopexy without transparenchymal fixation suturing: a 29-year experience. J Urol 2015;194:1743e7. [20] Backeljauw B, Holland SK, Altaye M, Loepke AW. Cognition and brain structure following early childhood surgery with anesthesia. Pediatrics 2015;136:e1e12. [21] Wilder RT, Flick RP, Sprung J, Katusic SK, Barbaresi WJ, Mickelson C, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009;110:769e804.
Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011
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Journal of Pediatric Urology (2017) xx, 1.e1e1.e5
Contralateral metachronous undescended testis: Is it predictable? Madeline Cancian a, Pamela Ellsworth b, Anthony Caldamone a Summary
possible predictors of subsequent UDT using PROC PHREG with SAS Software 9.4.
a
Department of Urology, Warren Alpert Medical School, Brown University, Providence, RI, USA
b
Division of Urology, Nemours Children’s Hospital, Orlando, FL, USA Correspondence to: M. Cancian, 2 Dudley Street, Suite 174, Providence, RI 02903, USA, Tel.: þ1 207 522 6718; fax: þ1 401 444 6947 [email protected] (M. Cancian) Keywords Undescended testis; Retractile testis; Acquired undescended testis Received 22 November 2016 Accepted 9 March 2017 Available online xxx
Introduction Metachronous undescended testis (mcUDT), an acquired UDT after contralateral orchiopexy, can occur in some boys. If one were able to predict its occurrence, one might consider a proactive approach or at least one would be able to counsel the parents accordingly. Our hypothesis was there may be characteristics evident at the time of initial orchiopexy which could predict the development of contralateral mcUDT. Objective The aim was to Identify factors present at initial orchiopexy that predict development of subsequent mcUDT. Study design Subjects were identified using the Current Procedural Terminology code for inguinal orchiopexy (54640). We included patients from January 1997 to October 2015. We included patients who underwent orchiopexy for unilateral UDT (uUDT). The study population consisted of patients who had undergone metachronous orchiopexies; controls were patients who were 17 years at time of data collection with a single orchiopexy. Cox proportional hazard regression was used to model the relationship between
Table
Results From 1035 eligible patients we identified 38 with mcUDT and 207 controls (uUDT). Median age at the first orchiopexy of mcUDT patients was 2.5 years (min/max, 0.50/10.4 years) and 8.2 years (min/max 0.70/12.8 years) for uUDT, p < 0.0001. Subjects with a contralateral retractile testis on preoperative exam had a 4.2 times higher rate of subsequent UDT than patients with a contralateral descended testis (95% CI 2.077e8.353). The rate of mcUDT was 6.7 times higher if the testis was a retractile testis under anesthesia (95% CI 2.7e16.5) (Table). Discussion Contralateral retractile UDT was a significant predictor of mcUDT. We believe patients with a contralateral retractile testis at time of orchiopexy should be counseled on bilateral orchiopexy. The risks of complications with orchiopexy should be weighed against risks of a subsequent surgery and anesthesia event. Conclusion A discussion of risks and benefits regarding bilateral orchiopexies should be undertaken with the parents prior to surgery in the setting of an UDT with contralateral retractile testis.
Patient characteristics and predictors of mcUDT.
Age at initial orchiopexy, years Congenital, % Contralateral examination in office (% retractile) Contralateral examination under anesthesia (% retractile) Ipsilateral PV open, %
Contralateral UDT (38)
Unilateral UDT (204)
p
2.5 65 52
8.2 52 18
<0.0001 0.10 <0.0001
22
2
<0.0001
48
59
0.14
PV Z processus vaginalis. http://dx.doi.org/10.1016/j.jpurol.2017.03.011 1477-5131/ª 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011
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1.e2
Introduction The incidence of congenital undescended testis (UDT), defined as a testis that has not descended prior to 6 months of age, is stated to be 1% [1]. It is recommended that these boys undergo orchiopexy between 6 and 12 months of age [2]. A significant number of boys undergo orchiopexy after 2 years of age, a phenomenon that is being increasingly recognized as a consequence of acquired UDT and not a missed diagnosis of congenital UDT [3e6]. Acquired UDT is defined as an undescended testis in a boy with a prior documented descended testis on the ipsilateral side. Both types of UDT carry an increased risk of testicular cancer [7] and decreased fertility potential [8]. The exact mechanism of acquired UDT is not understood; however, it is thought to be a variant of congenital UDT [9,10] and thus should carry the same potential sequelae [11]. Although the incidence is unknown, some boys develop metachronous UDT, requiring two separate orchiopexies. Our hypothesis was there may be characteristics evident at the time of initial orchiopexy that might predict the development of contralateral metachronous UDT.
Methods By database query using the Current Procedural Terminology code for inguinal orchiopexy (54640), we identified all patients with UDT between the dates of January 1997 and October 2015. We included all patients who underwent orchiopexy for the indication of UDT. We excluded patients who underwent orchiopexy for a testicular torsion or a contralateral orchiopexy in the finding of an ipsilateral testicular nubbin after inguinal exploration for UDT. We excluded all patients undergoing two-stage FowlereStephens procedures and patients with bilateral UDT at time of presentation. Through retrospective chart review we identified all patients who had undergone bilateral metachronous orchiopexy. Our control group comprised all patients who had undergone unilateral orchiopexy and were 17 years old at the time of data collection. We then collected data on age, type of UDT (congenital vs. acquired), physical examination in the office and under anesthesia, surgical approach, and surgical findings. UDT was considered congenital if present at birth by physician examination or by parental or primary care report, and acquired if the patient had a previously documented descended examination in our system or if a parent reported previous descended status. On examination, the testis was considered descended if it was in the scrotum at the time of examination. A testis was retractile if it could be brought into the scrotum and stayed after fatigue of the cremaster muscle. Physical examinations were identified both during a preoperative office visit and intraoperatively under anesthesia and prior to the start of the procedure. The surgical approach included prescrotal, inguinal, or one-stage laparoscopic orchiopexy. Note was also taken if the Prentiss maneuver was needed. The location of UDT was classified as able to pull into the scrotum but did not stay (prescrotal), superficial pouch, inguinal canal, or non-plapable. Because our center is the only pediatric urology one in the state, it was assumed that patients who had a prior
M. Cancian et al. orchiopexy for UDT would present to the same center if the contralateral testis ascended. With this is mind, we assumed that if a patient did not return, then they did not experience a contralateral UDT. Therefore, we right censored using time until their 17th birthday as “last known follow up” for controls. Seventeen was chosen as a conservative estimation of puberty and thus the point when secondary UDT could no longer occur. As a conservative effort, we removed all cases where first orchiopexy occurred over the age of 13; this was to allow a 4-year window by which a patient could experience a contralateral UDT. Data were collected and managed using REDCap electronic data capture tools hosted at our institution [12]. REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies, providing 1) an intuitive interface for validated data entry; 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for importing data from external sources. Cox proportional hazard regression was used to model the relationship between possible predictors of subsequent UDT using PROC PHREG with SAS Software 9.4. The time until orchidopexy was estimated using PROCLIFETEST.
Ethical approval Institute Review Board approval was obtained through our institution for this study.
Results We identified 1035 patients who were eligible for this study (Fig. 1). Of these patients, 50 had metachronous contralateral UDT (mcUDT) after initial orchiopexy, comprising 4.8% of the total UDT population. Among the remaining 985 patients, we identified 240 patients who were 17 at the time of data collection. We were able to obtain charts for 38 of the patients with mcUDT and 204 of the patients with unilateral UDT (uUDT) (Table 1). Comparing the 38 mcUDT patients with the 204 uUDT patients, the median age at the first orchiopexy of patients who had a subsequent orchiopexy was 2.5 years (min/max 0.50/10.4) and 8.2 years (min/max 70/12.8) for those who did not (p < 0.0001) (Fig. 1). The median time until subsequent orchiopexy in patients who developed a contralateral UDT was 3.5 years (95% CI 2.0e5.0 years). The median time between first orchiopexy and age of 17 for those who did not have a second orchiopexy was 8.9 years (95% CI 8.4e9.8). Contralateral testicular examination was significantly predictive of a subsequent UDT (p < 0.0001). Specifically, subjects who had a retractile testis on preoperative physical examination had a 4.2 times higher rate of subsequent UDT than patients who had a descended testis (95% CI 2.077e8.353). In addition, contralateral intraoperative testicular examination was significantly predictive of a subsequent UDT, p < 0.0001. Specifically, subjects who had a retractile testis under anesthesia had a 6.7 times higher rate of subsequent UDT than patients who had a descended
Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011
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Contralateral metachronous undescended testis
Figure 1
Table 1
1.e3
Inclusion and exclusion criteria.
Summary of patient characteristics.
Age at initial orchiopexy % Congenital Orchiopexy technique
Intraop ipsilateral testicular position
Prescrotal Inguinal Laparoscopic Prentiss Pulls down Superficial pouch Inguinal Nonpalpable
Contralateral exam in office (% retractile) Contralateral exam under anesthesia (% retractile) Ipsilateral PV open
testis (95% CI 2.7e16.5). In the patients who did not go on to have a mcUDT, 18% had a retractile testis in the office and only 2% had a retractile testis under anesthesia. Of note, the testicular examination preoperatively was missing in 3.7% of the population and the examination under anesthesia was missing in 7.5% of the population. No relationship was found for side of initial UDT (p Z 0.4947), acquired versus congenital UDT (p Z 0.40), procedure type (p Z 052), ipsilateral testicular position (p Z 0.71), size of ipsilateral UDT (p Z 0.21), and patency of the processus vaginalis (p Z 0.08).
Discussion Retractile testes, in the absence of contralateral UDT, are known to carry an increased risk of becoming undescended. Agarwal et al. [13] determined that retractile testes have a
mcUDT (38)
uUDT (204)
P value
2.5 yrs 65% 11 18 2 1 10 17 4 3 52% 22% 48%
8.2 yrs 52% 55 114 5 7 40 106 39 17 18% 2% 59%
<0.0001 0.1
<0.0001 <0.0001 0.14
32% chance of becoming undescended, with the risk being higher among boys <7 years old. Other series have shown a lower rate of ascent, from 3.2% to 14% [14,15]. These findings have led to a wait and see approach where the testis is given time to declare itself. Our findings show boys who have a contralateral retractile testis in the setting of a unilateral UDT have a 4e6.7 times increased likelihood of developing a UDT compared with boys with a normally descended contralateral testis. Thus in boys with contralateral retractile testis, especially under anesthesia, it may be worth performing bilateral orchiopexies to avoid a potential orchiopexy in the future. The greater risk of developing an UDT with a retractile testis under anesthesia than a retractile testis in the office examination is likely due to an underlying anatomic abnormality. As a retractile testis is due to a cremasteric reflex [13], boys under general anesthesia should have a decreased or absent cremasteric reflex. Boys who continue to have a
Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011
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1.e4 retractile testis while under anesthesia may have an underlying anatomic abnormality in addition to an active cremasteric muscle, which may contribute to a higher rate of subsequent UDT than in boys whose retractile testis becomes descended under anesthesia. The finding of a retractile testis under anesthesia is not common. It was present in 22% of the mcUDT population and only 2% of the uUDT population. With such a low prevalence in the uUDT population, there would be a low rate of unnecessary contralateral orchiopexies. Unfortunately, it is not understood what causes acquired UDT, so orchiopexy in the setting of a retractile testis cannot be guaranteed to prevent future UDT. Factors that have been hypothesized as contributing to acquired UDT include partial absorption of the processus vaginalis into the parietal peritoneum [16] or a fibrous remnant of the processus vaginalis inhibiting the stretch of the spermatic cord [17]. More recently, there has been enthusiasm for the theory that the spermatic cord is initially long enough for the testis to reach the low scrotum at birth however as the boy grows, a congenitally shortened cord tugs the testis back towards the inguinal canal [9]. At the time of orchiopexy, compared with congenital UDTs, acquired UDTs are typically closer to the scrotum and found in the superficial inguinal pouch, have a closed processus vaginalis, and have a normal attachment of the gubernaculum [18]. These findings support the theory of a shortened spermatic cord, and not a widely patent processus vaginalis or ectopic gubernacular attachment, leading to acquired UDT. Thus orchiopexy with lengthening of the spermatic cord to the internal ring by releasing the restrictive fibers should prevent the retractile testis from becoming undescended. To prove this theory, however, there would need to be a prospective trial. As with any procedure, the risks of preforming bilateral orchiopexy in the setting of a contralateral retractile testis must be weighed against the benefits. Undesirable outcomes following single-stage orchiopexy, including testicular atrophy, long-term pain, and suprascrotal location, are complications following 0.6% of procedures [19]. One must also factor in the extended anesthesia time, which may carry an increased cognitive risk; however, the data suggest an additional anesthesia event is more harmful than an extended event [20,21]. Owing to the nature of this study, we were unable to determine the incidence of metachronous contralateral UDT. However, since orchiopexy carries a low complication rate, consideration should be made for bilateral orchiopexy in patients with a contralateral retractile testis to avoid a second anesthesia and postoperative recovery in the future. There were many limitations to this study. The case and control population displayed significant differences in age at orchiopexy. To ensure the controls had no chance of developing a contralateral UDT, all control patients needed to be post-pubertal at the time of data collection. This consideration skewed our population towards an older age group. Despite the age disparity, there was no statistical difference between the type of UDT (congenital vs. acquired) in the two groups. Additionally, the type of UDT was not found to be predictive of subsequent contralateral UDT. We assumed that none of the control subjects went on to develop a contralateral UDT; however, we cannot be sure of this. This assumption was based on the fact that 1) ours is the
M. Cancian et al. only pediatric urology practice in the state, and 2) patients who had a developed relationship with a pediatric urologist would likely return to the same urologist if a new problem arose. In our practice patients are followed for 6 months after orchiopexy, so it is possible that some controls developed a contralateral UDT and obtained care elsewhere. However, we cannot account for nor control for patient migration. Despite these major limitations, our results show that presence of contralateral retractile testis at time of orchiopexy carries a four to six times odds of developing a contralateral UDT. At the time of orchiopexy, it is worth counseling the patient and family on the risks of developing a subsequent UDT and discussing a possible prophylactic contralateral orchiopexy.
Conclusion Boys who have a contralateral retractile testis at the time of ipsilateral orchiopexy have a four to six times odds ratio of developing a contralateral UDT compared with boys with a normally descended contralateral testis. Consideration should be given to bilateral orchiopexy in this setting or, at the least, these boys and their families should be counseled on the risk of a future surgery.
Conflict of interest None.
Funding None.
Acknowledgment We would like to thank Grayson Baird for his assistance on the statistical analysis and Drs Richard Caesar and Leslie Tackett for the use of their patients in this study.
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Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011
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Please cite this article in press as: Cancian M, et al., Contralateral metachronous undescended testis: Is it predictable?, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.03.011