Pediatric Cryptorchidism Surgery
- Author: Marcos Perez-Brayfield, MD; Chief Editor: Marc Cendron, MD more...
Cryptorchidism (from Greek kryptos "hidden" and orchis "testis") is the most common abnormality of male sexual development. In this condition, the testis is not located in the scrotum. It can be ectopic, incompletely descended, retractile, and absent or atrophic.
Sir John Hunter, the British anatomist, reported this condition in 1786. In 1877, Annandale performed the first successful orchidopexy. In 1899, Bevan published the principles of testicular mobilization, separation of the processus vaginalis, and repositioning of the testis into the scrotum. Since then, testicular maldescent has been the subject of many clinical studies, but its embryology, effects on fertility, and ultimate clinical impact still remain topics of discussion and research.
Embryology of testis development
The embryology of testis development is critical to understanding the most common theories that explain cryptorchidism.
Shortly after 6 weeks' gestation, the testis-determining SRY gene on chromosome Y directly affects the differentiation of the indifferent gonad into a testis. Germ cells are located in the germinal ridge close to the kidney in the retroperitoneum. Around 6-7 weeks' gestation, Sertoli cells develop and secrete müllerian inhibitory substance (MIS; also known as antimüllerian hormone [AMH]), which leads to the regression of the female genital organs.
Around 9 weeks' gestation, Leydig cells start producing testosterone, which promotes development of the wolffian duct into portions of the male genital tract. Concurrently, the testis organizes as a distinct organ with its distinct seminiferous tubules surrounded by vessels and encapsulated by the tunica albuginea. Owing to the differential growth of the fetus, the testicles move into the pelvis, close to the internal ring.
The testis remains in a retroperitoneal position until 28 weeks' gestation, at which time inguinal descent of the testicle begins. Most testes have completed their descent into the scrotum by 40 weeks' gestation.
Theories of pathophysiology of cryptorchidism
Several potential explanations for the pathophysiology of cryptorchidism have been propsoed, including gubernacular abnormalities, reduced intra-abdominal pressures, intrinsic testicular and/or epididymal abnormalities, and endocrine abnormalities, as well as anatomic anomalies (eg, fibrous bands within the inguinal canal or abnormal arrangement of the cremasteric muscle fibers).
The gubernaculum testis is a structure that attaches the lower portion of the tunica vaginalis to base of the scrotum. The gubernaculum is thought to aid in testicular descent by widening the inguinal canal and guiding the testis down to the scrotum. Therefore, anomalies in this attachment may contribute to cryptorchidism.
Cryptorchidism is common in patients with prune belly syndrome and those with gastroschisis; both are associated with decreased intra-abdominal pressures. However, the theory based on reduced pressures does not explain most cases of cryptorchidism.
Another theory of testicular maldescent is based on intrinsic testicular or epididymal abnormalities. Several studies have shown that the germinal epithelium of the maldescended testis may be histologically abnormal. Infertility is associated with cryptorchidism, and the risk of infertility increases with the degree of maldescent. Moreover, approximately 23-86% of maldescended testes have been associated with some form of epididymal abnormality. Studies have shown an increase in the degree of epididymal abnormalities in intra-abdominal testis in comparison with mild cases of cryptorchidism.
Abnormalities in the hypothalamic-pituitary-gonadal axis have been postulated as a possible explanation for anomalies of testicular descent and abnormal germ-cell development. However, both animal and human endocrine studies have not been able to shed clear light on the pathophysiology of testicular maldescent. The causative hormonal abnormality may be found at different levels. That the condition most often affects one side indicates that endocrine anomalies may be partially responsible but does not completely explain why the testis does not descend normally.
The molecular mechanisms by which the newly determined testicle descends from its position in the posterior abdomen into the scrotum is a complex process that likely involves multiple genetic, hormonal, environmental, and stochastic factors. Although a comprehensive explanation has not yet been elucidated, several exciting observations suggest that specific genetic loci play important roles in normal testicular descent and the occurrence of cryptorchidism.
Models for the study of cryptorchidism include experiments in knockout mice. Homozygous mutants for the loss of HOXA10 and HOXA11 exhibit cryptorchidism. Both genes are members of the family of homeobox genes, which are highly conserved throughout evolution and which play a critical role in anteroposterior positioning in the developing embryo. Early orchiopexy rescues HOXA11 mutants from an infertile state. HOXA10 polymorphisms have been found in human cryptorchid populations, though their functional significance has not yet been established.
In the literature, much attention has been focused on insulinlike factor 3 (INSL3) and its receptor, leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8), or G-protein–coupled receptor affecting testes descent (GREAT). Homozygous knockouts of either INSL3 or LGR8 lead to the phenotype of bilateral intra-abdominal testes. As in the murine HOXA11 model, early orchiopexy of INSL3-genetically deficient mice allows for the development of fertility.
Although some have suggested that mutations in the INSL3 gene might not play a substantial role in human cryptorchidism, a missense mutation in INSL3 has been found in a patient with cryptorchidism; this mutation causes a nonconservative amino acid substitution. A proof-of-principle study has not yet been conducted to determine whether this INSL3 mutation leads to cryptorchidism.
LGR8 polymorphisms have been identified in both cryptorchid and healthy human populations. One of the receptor mutations found in a cryptorchid patient precluded a response to ligand stimulation in vitro.
In the search for a genetic cause of cryptorchidism, other areas of focus include Y-chromosome microdeletions, increased aromatase activity, and abnormalities in the Wilms tumor gene (WT1).
A palpable undescended testis is found in 3-5% of newborns, and bilateral undescended testis is found in 15% of newborns with cryptorchidism. Most undescended palpable testes later spontaneously descend within the first 4 months of life; only 0.7-1% of 1-year-old infants have a persistent undescended testis. Studies have shown that spontaneous descent does not occur after age 9 months. The incidence does not change between age 1 year and adulthood. However, some testes that were descended in early childhood may ascend later in life.
Nonpalpable testes account for approximately 20% of all undescended testes. Approximately 40% of the nonpalpable testes are intra-abdominal, 40% are inguinal, and 20% are atrophic or absent (Vanishing Testis Syndrome).
Cryptorchidism is found in 30% of babies born prematurely. Other predisposing factors include low birth weight, small size for gestational age, twin pregnancy, and maternal estrogen exposure. Cryptorchidism is found in 7% of siblings and in about 2% of fathers of babies with this condition.
Cryptorchidism affects only males and has no reported racial predilection.
Success of surgical treatment
Orchiopexy for palpable testis (scrotal, inguinal, and suprainguinal) has a success rate in the range of 80-90% as measured by the testicle being in a normal anatomic position.
Orchiopexy for nonpalpable testis has different reported success rates ( as measured by testis in normal position and felt to be viable) in different surgical scenarios, as follows:
Inguinal approach - 60%-88%
Suprainguinal approach - Up to 95%
One-stage Fowler-Stephens procedure - 67%-96%
Two-stage Fowler-Stephens procedure - 77%-95%
Microvascular transplantation - 83%-96%
Laparoscopic orchiopexy - 80%-95%
Laparoscopic Fowler-Stephens procedure - Up to 96%
Mortality and morbidity
Cryptorchidism has not been associated with any factors for mortality. However, testicular maldescent has been associated with a slight increase in the risk of testicular cancer, infertility, trauma, and testicular torsion. If not treated, testicular maldescent may also affect the psychological well-being of young men in whom negative self-esteem issues may arise.
In patients with cryptorchidism, the risk of testicular cancer is 3-5%, a 4- to 7-fold greater risk than the 0.3-0.7% reported in the healthy population. The most common tumor in an undescended testis is a seminoma, whereas the most common tumor after successful orchiopexy is nonseminomatous germ-cell tumor. Approximately 20% of these tumors occur in a contralateral descended testis.
Carcinoma in situ occurs in approximately 0.4% of patients undergoing orchiopexy. Orchiopexy is not protective against subsequent testis cancer but does place the testis in a favorable position for routine self-examination, which is important in the early recognition of testicular cancer. The patient and family must be educated about the risk of future testicular cancer.
Approximately 6% of infertile men have a history of orchiopexy or untreated cryptorchidism. The rate of infertility is higher in patients with bilateral cryptorchidism than in those with unilateral cryptorchidism or in the general male population. The paternity rate for patients with bilateral cryptorchidism is around 60% versus 90% in patients with unilateral cryptorchidism. The rate in those with unilateral cryptorchidism is slightly less than the 94% in the general population.
The location of the undescended testis may play a role in fertility potential. Worsening testicular biopsy findings are correlated with high locations (eg, intra-abdominal testis).
Normal spermatogram findings are found in 20% of patients with bilateral undescended testis compared with 75% of patients with unilateral cryptorchidism.
The decision to perform orchiopexy in patients younger than 24 months might be made because testicular biopsy shows that the rate of germ-cell aplasia substantially increases after age 2 years. Long-term studies are needed to determine the true effect of early orchiopexy on fertility.
One evaluation of the referral practices of local pediatricians showed that physicians tended to refer patients for treatment at a mean age of around 4 years. This finding shows the importance of educating primary physicians about the timing of surgery (before age 1 year) and the benefits of early surgical intervention.
The patient and his family should be informed about the risks of infertility and malignancy. Self-examination after the onset of puberty should be discussed as very important for the early diagnosis and successful treatment of testicular cancer.
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