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Individualized Treatment Guidelines for Postpubertal Cryptorchidism

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Individualized Treatment Guidelines for Postpubertal Cryptorchidism pISSN: 2287-4208 / eISSN: 2287-4690 World J Mens Health 2015 December 33(3): 161-166 http://dx.doi.org/10.5534/wjmh.2015.33.3.161 Review Article Individualized Treatment Guidelines for Postpubertal Cryptorchidism Jae Min Chung1,2, Sang Don Lee1,2 1Department of Urology, Pusan National University School of Medicine, 2Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea Cryptorchidism is a well-known congenital anomaly in children. However, its diagnosis is often delayed for reasons including patient unawareness or denial of abnormal findings in the testis. Moreover, it has been difficult to establish an optimal treatment strategy for postpubertal cryptorchidism, given the small number of patients. Unlike cryptorchidism in children, postpubertal cryptorchidism is associated with an increased probability of neoplasms, which has led orchiectomy to be the recommended treatment. However, routine orchiectomy should be avoided in some cases due to quality-of-life issues and the potential risk of perioperative mortality. Based on a literature review, this study proposes individualized treatment guidelines for postpubertal cryptorchidism. Key Words: Adolescent; Adult; Cryptorchidism INTRODUCTION egies for cryptorchidism in children are well-established. A surgical approach, most often orchiopexy, is recom- Cryptorchidism is a pathological condition in which the mended for testes that remain undescended after six testis fails to descend to the base of the scrotum. It is one months of age [3]. However, it has been difficult to estab- of the most common congenital anomalies encountered in lish a standard treatment for postpubertal cryptorchidism, pediatric urology. Despite extensive study, knowledge re- given the small number of patients with this condition. garding the etiology and eventual consequences of cryp- Unlike cryptorchidism in children, postpubertal cryp- torchidism remains limited. Cryptorchidism occurs in 1% torchidism is associated with an increased probability of to 4% of full-term and 1% to 45% of preterm male neo- neoplasms, which has led orchiectomy to be the recom- nates [1]. Its prevalence reaches approximately 1% by the mended treatment [4]. However, routine orchiectomy age of one year, while relatively few cases are newly diag- should be avoided for several reasons. Therefore, we per- nosed in patients older than one year [2]. Treatment strat- formed a literature review to identify individualized treat- Received: Aug 14, 2015; Revised: Oct 6, 2015; Accepted: Nov 4, 2015 Correspondence to: Sang Don Lee Department of Urology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea. Tel: +82-55-360-2671, Fax: +82-55-360-2164, E-mail: [email protected] Copyright © 2015 Korean Society for Sexual Medicine and Andrology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 162 World J Mens Health Vol. 33, No. 3, December 2015 ment guidelines for postpubertal cryptorchidism. SPERMATOGENESIS AND BIOPSY RELEVANT CLINICAL FACTORS Untreated cryptorchidism has been definitively asso- ciated with infertility. The development of postnatal germ The diagnosis and treatment of postpubertal cryptorch- cells deteriorates in the undescended testis after the first idism and prepubertal cryptorchidism are markedly differ- year, and perhaps for this reason, the risk of infertility in- ent processes. A physician encountering postpubertal creases with age [9-11]. cryptorchidism during an office examination should con- In a study of 767 boys with unilateral cryptorchidism sider the risk of testicular cancer development, impacts on who underwent orchidopexy and bilateral testicular biop- spermatogenesis, altered endocrine function, the patient’s sies between birth and nine years of age, gonocytes failed cosmetic appearance, the condition of the contralateral to disappear and adult dark spermatogonia failed to ap- testis, and other factors including torsion, trauma, and as- pear in the undescended testes in patients under one year sociated hernia. The most important factor affecting mor- of age, indicating a defect in the first step of testicular ma- tality is the risk of testicular cancer. The second most im- turation at two to three months that resulted in the absence portant factor is fertility, which is most intensely affected of an adequate adult stem cell pool [12]. In the same study, by alterations in endocrine function and spermatogenesis. primary spermatocytes failed to appear in undescended testes and appeared in only 19% of contralateral de- RISK OF CANCER DEVELOPMENT scended testes at four to five years of age, indicating a de- fect in the initiation of meiosis. The clinical importance of cryptorchidism is mainly due In a study of 12 patients who underwent testis biopsies, to the risk of testicular cancer, as approximately 10% of all subjects with unilateral adult cryptorchidism had ab- testicular tumors are believed to arise from cryptoid testes. normal histologic findings [4]. Three of the four patients The relative risk of neoplastic changes in undescended who underwent preoperative semen analysis showed ab- testes is 40 times higher than in descended testes [3]. The normal findings. However, four of the six married patients estimated rate of in situ carcinoma in patients with cryp- had children. All of the patients with bilateral cryptorchid- torchidism is approximately 1.7% [5]. The effect of orchi- ism showed abnormal findings in the histology of the testis opexy on testicular tumors remains controversial, al- and in semen analysis, and none had children. though prepubertal orchiopexy may reduce the risk of tu- mor formation in undescended testes [6]. ENDOCRINE FUNCTION In a large cohort study of 16,983 men who were surgi- cally treated for cryptorchidism, the risk of testicular can- Although Leydig cells are less vulnerable to damage, cer among those treated at 13 years of age or older was ap- endocrine function is impaired in postpubertal cryptorchi- proximately twice that of men who underwent orchiopexy dism. Leydig cell hyperplasia is present in adults with un- before the age of 13 years [7]. In a systematic review, the corrected cryptorchidism [13]. Immunohistologic evi- risk of testicular cancer in patients with cryptorchidism dence of reduced functional Leydig cell activity is also was found to be increased by 74% in the contralateral tes- present in such cases [14]. The assessment of the presence tis, in contrast to the more than six-fold increase in risk on and function of Leydig cells in adults with cryptorchidism the ipsilateral side [8]. The authors concluded that in cases suggests that men with cryptorchidism do not have com- of unilateral cryptorchidism, the risk of testicular cancer promised Leydig cell function unless the intertubular con- may be increased on both sides, although to a much great- nective tissue is damaged, which is associated with absent er extent on the ipsilateral side. The results indicate that or altered Leydig cells [15]. both the ectopic position of the testis and shared risk fac- A study investigated the endocrine function of patients tors are involved in the mechanism behind the association with cryptorchidism to determine differences in the func- between cryptorchidism and testicular cancer. tion of the Leydig cell-pituitary axis in formerly unilateral Jae Min Chung and Sang Don Lee: Treatment of Postpubertal Cryptorchidism 163 cryptorchid men [16]. The following variables were ana- [21] reported successful testicular sperm extraction and lyzed in subjects and in controls: luteinizing hormone; tes- paternity in an azoospermic man after bilateral post- tosterone; free testosterone; follicle-stimulating hormone; pubertal orchiopexy. inhibin B; sperm density, motility and morphology; tes- In a series of 25 males (29 testes) presenting at a post- ticular volume; and patient weight and age at orchiopexy pubertal age with cryptorchidism, orchiectomy was per- or at the time of other childhood surgery (in controls). Men formed in 22 testes and orchiopexy for the remaining who underwent orchiopexy later in childhood displayed seven. The testes had been in an anomalous location for subclinically decreased Leydig cell function, which could between 20 and 51 years. One of the testes was found to potentially result in a hormonal milieu that would be less have a malignancy consisting of a pure seminoma. In the than optimal for adult reproductive function. subsequent follow-up period, none of the patients in ei- With regard to the overall endocrine function of pa- ther group (orchiopexy or orchiectomy) developed a ma- tients with cryptorchidism, hormone replacement therapy lignancy in the contralateral testis [23]. can be considered after bilateral orchiectomy in cases in- In another series of 81 patients presenting after the age volving bilateral nonpalpable testes. of 14 years with either unilateral or bilateral cryptorchid- ism, two patients developed a testicular malignancy. Most TREATMENT OF POSTPUBERTAL of the cases (93%) had secretory azoospermia in associa- CRYPTORCHIDISM tion with seminiferous abnormalities and
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