| disease | Cryptorchidism |
The descent of the testes and epididymis is crucial for the normal development and spermatogenesis of the testes. The XY genetic code is a significant gene for male sexual characteristics and testicular formation. Endocrine, genetic, and physical mechanical factors can affect the normal descent of the testes.
bubble_chart Epidemiology
The incidence of cryptorchidism is 0.7% to 0.8% (Cour Palais Scorer). The incidence is directly related to fetal development, with a rate of up to 30% in immature fetuses, 3.4% at birth in full-term mature infants, and 0.7% to 0.8% by the age of one.
During embryonic development, the normal descent of the testes is influenced by endocrine hormones and physical mechanical factors. The descent of the testes is divided into two stages. The first stage includes embryonic differentiation, testicular formation, and movement from the urogenital ridge to the inguinal region. The second stage involves the movement of the testes from the inguinal region into the scrotum, which is primarily controlled by hormones. Physical mechanical factors affecting testicular descent include: ① the traction effect of the gubernaculum with the cremaster muscle, ② intra-abdominal pressure pushing the testes into the scrotum, and ③ normal epididymal development, which also contributes to testicular descent. Endocrine factors mainly refer to abnormalities in the hypothalamic-pituitary-testicular axis, which can lead to cryptorchidism. Additionally, Müllerian inhibiting substance (MIS) secreted by Sertoli cells, as well as male hormones such as testosterone and dihydrotestosterone, also influence testicular descent. In patients with Kallmann syndrome, a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) often results in cryptorchidism. Gendel reported that serum levels of luteinizing hormone (LH) in cryptorchid patients are lower than in normal individuals. Walsh et al. demonstrated that patients with 5α-reductase deficiency cannot effectively convert testosterone to dihydrotestosterone, which is sufficient to affect testicular descent and lead to cryptorchidism. In summary, testicular descent is a highly complex embryonic developmental process influenced by endocrine, genetic, and physical mechanical factors. Abnormalities in these combined factors can all contribute to the occurrence of cryptorchidism.
bubble_chart Pathological ChangesThe longer the abnormal position of cryptorchidism persists, the higher the location, the greater the damage to the testis. After 1.5 to 2 years of age, the main histological changes in the testis include the shrinkage of seminiferous tubules, scanty sperm production, and increased peritubular tissue (Cooper, Mengel). The number of interstitial cells may increase or decrease, while the number of Sertoli cells increases. Hadyiselimovic et al., after conducting electron microscopic studies on cryptorchidism, found that the testicular changes in cryptorchid patients include: ① destruction of intracellular mitochondria; ② lack of ribosomes in the cytoplasm and endoplasmic reticulum; ③ increased collagen fibers in spermatogenic cells and Sertoli cells. Moreover, if it is unilateral cryptorchidism, the contralateral testis that has descended normally into the scrotum may also exhibit pathological changes.
bubble_chart Clinical Manifestations
Classification of Cryptorchidism:
The classification methods of cryptorchidism include classifications based on the cause of the disease, the location of the cryptorchidism, and the nature of the cryptorchidism.
King classified cryptorchidism based on the cause as follows:
(1) Dysplasia of the terminal organ, where the testis is smaller than normal with a small number of germ cells, often accompanied by abnormal duct structures.
(2) Ectopic testis, where the testis descends through the inguinal canal but settles in a location outside the scrotum.
(3) Abnormal gonadotropin stimulation, including endocrine abnormalities that can cause cryptorchidism.
(4) Mechanical factors (such as atresia of the inguinal canal).
Hinman and Hopp also proposed other classification methods.
It is generally believed that the following classification method is more practical in clinical settings:
(1) Retractile testis.
(2) True cryptorchidism:
① High intra-abdominal cryptorchidism;
② Inguinal cryptorchidism;
③ High scrotal cryptorchidism;
④ Sliding cryptorchidism.
(3) Ectopic testis.
(4) Anorchia (unilateral or bilateral anorchia).
A retractile testis refers to an overly active cremaster muscle, where the testis can retract above the scrotum, but can be manually placed into the scrotum during rest at night or during examination. These patients have normal testicular position and size after puberty, with fertility similar to normal individuals. Ectopic testis refers to the testis being located outside the scrotum, above the pubis, in the thigh, perineum, base of the penis, or in a transverse position, and should be surgically corrected. Anorchia is often caused by torsion of the spermatic cord within the uterus during pregnancy.
Abnormalities associated with cryptorchidism:
Cryptorchidism can be an isolated condition or associated with other genitourinary system abnormalities, endocrine diseases, and genetic disorders.
Felton reported 658 cases of cryptorchidism, with 2.5% associated with significant urinary system abnormalities, mainly unilateral duplicated kidney, renal ectopia, renal atrophy, hydronephrosis, horseshoe kidney, duplicated ureter, and stenosis at the ureteropelvic junction. Cryptorchidism patients may also have hypospadias and congenital posterior urethral valves.
Both autosomal and sex chromosome abnormalities can cause cryptorchidism. Common genetic endocrine syndromes associated with cryptorchidism include:
(1) Kallmann syndrome: An X-linked recessive disorder with low gonadotropin-releasing hormone secretion, hypogonadism, and often cryptorchidism.
(2) Klinefelter syndrome (small testis syndrome): Patients exhibit anorchia-like body type, gynecomastia, cryptorchidism with small and hard testes, hyalinization and fibrosis of the seminiferous tubules, and inability to produce sperm.
(3) Noonan syndrome (male Turner syndrome): Patients often have facial abnormalities, cardiovascular abnormalities, urinary system abnormalities, and cryptorchidism (70%).
(4) Other conditions such as Prader-Willi syndrome, Down syndrome, Aarkog syndrome, and other genetic and endocrine syndromes are often accompanied by cryptorchidism.
Patients with true and pseudohermaphroditism often have complex genetic and endocrine abnormalities. If the patient has cryptorchidism, detailed genetic and endocrinological examinations must be conducted before further treatment.
If the cryptorchid testis is located within the inguinal canal and high in the abdomen or if the testis is absent, it is often not palpable during clinical examination. Levitt's statistics show that about 20% of all cryptorchid testes are not palpable during clinical examination. For these patients, an HCG stimulation test is often performed first, which involves injecting 1500IU of HCG every other day for a total of three times. The serum testosterone levels are checked before and after the injection. If the serum testosterone level increases after the injection, it indicates the presence of functional testicular tissue. If the serum testosterone level remains unchanged, it often indicates the absence of functional testicular tissue.
For clinically non-palpable cryptorchid testes, special diagnostic methods are often required for localization. B-mode ultrasound is currently the most commonly used method. This examination is non-invasive and can simultaneously check for hydronephrosis, malformations, stones, and other urinary system lesions in the patient. It has a fairly high diagnostic rate for cryptorchid testes within the inguinal canal, but the diagnostic rate for intra-abdominal cryptorchid testes is not high enough. Selective internal spermatic vein angiography was once a widely used method, which could diagnose the position of the cryptorchid testis or the absence of the testis from the morphology of the end of the internal spermatic vein after the injection of the contrast agent. However, it is often affected by venous valves, making it difficult to perform on children under 2 years old. Computed tomography (CT Scan) and magnetic resonance imaging (MRI) have also been used in recent years for the localization diagnosis of intra-abdominal cryptorchid testes, both with considerable accuracy. Wolverson reported a 96% accuracy rate in 20 patients who underwent CT examination; Fritzche reported that 14 out of 15 cryptorchid testes in 12 patients were confirmed by MRI, with one case of high misdiagnosis. The drawbacks of these two examinations are that they are relatively difficult to perform on young children and are very expensive.
Laparoscopy has been widely used in recent years for the diagnosis and treatment of intra-abdominal cryptorchid testes. Laparoscopy has a wide range of applications, can be used for patients of all ages and children under 1 year old, has a simple operation method and short time, and a diagnostic rate of 88% to 100%. It can determine the position of the cryptorchid testis or the absence of the testis. During laparoscopy, the testicular vessels can often be found first along the anatomical position of the testicular vessels behind the abdominal membrane. The testis located in the abdomen or at the internal inguinal ring can be found along the spermatic cord vessels. If a blind end of the vessel is seen along the vessel, it can be determined that the testis is absent. If there is a nodule at the blind end, it should be removed and sent for pathological examination. Diamond summarized three outcomes of laparoscopy for clinically non-palpable cryptorchid testes: ① The blind end of the spermatic cord vessels and vas deferens is seen above the internal inguinal ring, lacking the testis; ② The normal spermatic cord enters the internal inguinal ring; ③ Intra-abdominal testis. The latter requires surgical exploration. If only the vas deferens is seen entering the inguinal canal without seeing the spermatic cord vessels during the examination, exploratory laparotomy should also be performed. If high intra-abdominal cryptorchid testes and a long vas deferens are observed during the examination, a staged orchiopexy initial stage [first stage] surgery can be performed, which involves separating, clamping, and cutting the spermatic cord vessels, leaving the intermediate stage [second stage] orchiopexy for later. If abnormal testicular development is found during the operation, staged orchiopexy should be performed, and orchiectomy should be performed via laparoscopy.
bubble_chart Treatment Measures
The treatment of cryptorchidism involves bringing the testis from an abnormal position to its normal location. The treatment of cryptorchidism is primarily based on the following main reasons: ① Due to the abnormal position of the cryptorchid testis, the normal spermatogenic ability of the testis is impaired, and bringing the testis down can increase spermatogenesis; ② Since the incidence of malignant transformation in cryptorchidism is relatively high, the testis should be placed in the scrotum to facilitate early detection of lesions; ③ To relieve the psychological stress factors in children and their parents. The treatment time for cryptorchidism is within 2 years of age, and the main treatment methods include hormone therapy and orchiopexy.
Hormone therapy refers to the use of gonadotropins or gonadotropin-releasing hormones to adjust the hypothalamic-pituitary-testicular endocrine axis to promote the descent of the cryptorchid testis. HCG (Human Chorionic Gonadotropin) treatment involves using an injection dose of 3000IU to 40000IU, administered over several days to a cycle of day and night. The current common regimen is: for ages 1 to 6, use HCG 250IU, twice a week for 5 weeks; for ages 1 to 6, use 500IU, twice a week for 5 weeks; for ages over 6, use 100IU, twice a week for 5 weeks. The descent rate for bilateral cryptorchidism is around 30～50%, while for unilateral cryptorchidism, it is around 15～30%. Gonadotropin-releasing hormone (GnRH) or LHRH (Luteinizing Hormone Releasing Hormone) has been increasingly used in recent years, often administered via nasal spray, 200μg per nostril, three times a day for four weeks, with a success rate ranging from 10～60%. Rajfer believes that the wide variation in success rates is due to some authors including retractile cryptorchidism in their calculations, which has a high success rate with hormone therapy.
Orchiopexy is the main treatment for cryptorchidism, and during surgical treatment, concurrent inguinal hernias can also be treated. The principle of surgical treatment is to use an appropriate lower abdominal incision, fully mobilize the spermatic cord during surgery, repair the hernia sac, and fix the testis in the scrotum. The standard orchiopexy involves making an oblique inguinal incision, repairing the hernia sac, mobilizing the testis and spermatic cord, and then placing the testis into the scrotum and fixing it. During the surgery, care is taken to ensure that the spermatic cord is tension-free after fixing the testis, to ensure the blood supply to the testis.
For some patients with high intra-abdominal cryptorchidism, the vas deferens is long and curved in the inguinal canal, and a procedure to cut the spermatic cord vessels and lower the testis (Fowler-Stephen surgery) can be performed. Alternatively, a staged surgery can be done, where the initial stage [first stage] involves cutting the spermatic cord vessels, and the intermediate stage [second stage] involves lowering the testis.
A few patients with high intra-abdominal cryptorchidism may require testicular autotransplantation, which involves cutting the spermatic cord vessels, anastomosing the internal stirred pulse and veins of the spermatic cord with the deep stirred pulse and veins of the abdominal wall, and placing the testis in the scrotum. This surgical method requires microsurgical techniques.
Both unilateral and bilateral cryptorchidism, especially when treated early, can help improve the development of spermatogonia, increase the number of spermatogonia, and enhance spermatogenesis after puberty. Lipshulty reported in a follow-up study of unilateral cryptorchidism patients that 62% of those who underwent surgery before puberty had fertility after puberty, compared to only 46% in those who did not undergo surgery.
The timing of surgical treatment is also closely related to post-pubertal fertility. Ludwig reported in a group of patients that 87.7% of those who underwent surgery between 1～2 years of age had normal fertility as adults, while 57.1% of those who underwent surgery between 3～4 years of age had normal fertility.
Complications of Cryptorchidism:
Cryptorchidism and infertility. Due to histopathological changes, cryptorchidism lacks normal spermatogenic function. The higher the position of the cryptorchid testis and the longer it remains above the scrotum, the greater the damage to the seminiferous tubules. Mengel observed through light and electron microscopy that pathological changes in the seminiferous tubules and interstitial cells, as well as significant spermatogenic damage, occur in cryptorchid patients before the age of 2. Hecker compared sperm concentrations in normal adults and unilateral cryptorchid patients after orchiopexy, finding that the former was significantly higher than the latter, indicating bilateral testicular damage in unilateral cryptorchid patients. Untreated bilateral cryptorchidism can lead to infertility in 100% of cases, but early treatment can restore fertility to 40%. For unilateral cryptorchidism, early treatment can achieve a fertility rate of 60%. Treatment before the age of 2 helps improve the development of spermatogonia, increasing their number and subsequent spermatogenesis. However, even with early treatment, the spermatogenic ability of both unilateral and bilateral cryptorchid patients remains lower than normal in adulthood.
Cryptorchidism and testicular torsion. Due to developmental abnormalities between the testis and its mesentery in cryptorchid patients, testicular torsion is more likely to occur. The risk increases after puberty due to the enlargement of the testis. Rigter reported that 64% of adult cryptorchid torsion cases are caused by malignant changes in the testis, leading to changes in testicular weight and the axis of gravity. The treatment principle is orchiopexy or, if necessary, orchiectomy.
Cryptorchidism and malignant transformation:
Cryptorchid patients have a high risk of malignant transformation after puberty. The incidence of malignant transformation in cryptorchidism is 25 to 48 times higher than in normal individuals (Whiter and Welvar). Approximately 10% of testicular tumors occur in cryptorchid testes. Due to histological abnormalities in cryptorchidism, early surgery cannot prevent malignant transformation. In unilateral cryptorchid patients, the contralateral testis, even if descended into the scrotum, also shows histological abnormalities and has a higher risk of malignant transformation. Johnson found that in unilateral cryptorchid patients with malignant transformation, one-fifth of the malignancies occurred in the non-cryptorchid testis. In bilateral cryptorchid patients, if one side undergoes malignant transformation, the other side has a 15% chance of also undergoing malignant transformation.
The position of the cryptorchid testis is significantly related to malignant transformation. Intra-abdominal cryptorchidism has a fourfold higher risk of malignant transformation compared to inguinal cryptorchidism. In bilateral intra-abdominal cryptorchidism, if one side undergoes malignant transformation, the other side has a 30% chance of also undergoing malignant transformation.
Skakkebaek discovered carcinoma in situ in biopsies of cryptorchid patients, leading to a new understanding of malignant transformation in cryptorchidism, with an incidence rate of 30%.
In summary, to monitor changes in cryptorchidism and detect malignant transformation early, orchiopexy should be performed as early as possible, especially for intra-abdominal cryptorchidism, which should be moved into the scrotum early. If it cannot be moved into the scrotum, orchiectomy should be performed. After malignant transformation in cryptorchidism, which is often seminoma, radical orchiectomy and retroperitoneal radiation therapy should be promptly administered.
